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WO2025099576A1 - Compositions et méthodes de traitement de la polyarthrite rhumatoïde - Google Patents

Compositions et méthodes de traitement de la polyarthrite rhumatoïde Download PDF

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Publication number
WO2025099576A1
WO2025099576A1 PCT/IB2024/060934 IB2024060934W WO2025099576A1 WO 2025099576 A1 WO2025099576 A1 WO 2025099576A1 IB 2024060934 W IB2024060934 W IB 2024060934W WO 2025099576 A1 WO2025099576 A1 WO 2025099576A1
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Prior art keywords
agent
fcrn
weeks
subject
seq
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Kaiyin FEI
Sheng GAO
Rohit PANCHAKSHARI
Matthew LOZA
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Momenta Pharmaceuticals Inc
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Momenta Pharmaceuticals Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/10—Musculoskeletal or connective tissue disorders
    • G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
    • G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the present application relates to treating or reducing severity of rheumatoid arthritis in a subject.
  • RA Rheumatoid arthritis
  • RA is a chronic autoimmune inflammatory disorder of unknown etiology that occurs in approximately 1% of the population (Alamanos Y, Drosos A. Epidemiology of adult rheumatoid arthritis. Autoimmunity Reviews. 2005;4(3): 130-136.2015).
  • RA is more prevalent among women than men and usually develops in the fourth or fifth decades of life, with 80% of the total cases occurring between the ages of 35 and 50.
  • Joint inflammation underlies the cardinal manifestations of this disease, which include pain, stiffness, swelling, and tenderness in the joints followed by cartilage destruction, bone erosion, and subsequent deformities, resulting in impaired physical function.
  • an anti-neonatal Fc receptor (FcRn) agent to the subject, wherein, prior to the subject receiving an initial administration of the anti-FcRn agent, an anti-citrullinated protein antibody (ACPA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level.
  • an anti-FcRn agent is nipocalimab.
  • step (b) administering an anti-neonatal Fc receptor (FcRn) agent to the subject if the ACPA level determined in step (a) is higher than an ACPA reference level.
  • the anti- FcRn agent is nipocalimab.
  • the blood sample is serum sample.
  • the ACPA reference level is within a range from about 100- 1000 U/ml.
  • the ACPA reference level is about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or 1000 U/ml.
  • the ACPA reference level is within a range from about 400-600 U/ml.
  • the ACPA level in the blood sample is determined using an ELISA assay. In some embodiments, the ACPA level in the blood sample is determined using a cyclic citrullinated peptides (CCP) assay.
  • CCP cyclic citrullinated peptides
  • the ACPA level in the blood sample is determined using a CCP2 assay.
  • the ACPA level in the blood sample is determined using a CCP3 assay.
  • the subject has not been previously treated with a diseasemodifying antirheumatic drug (DMARD). In some embodiments, the subject demonstrated inadequate response to or is intolerant to at least one disease-modifying antirheumatic drug (DMARD).
  • the DMARD is an anti-tumor necrosis factor (TNF) agent.
  • the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab. In some embodiments, the anti-TNF agent is adalimumab, etanercept, golimumab, or infliximab.
  • the DMARD is a JAK inhibitor. In some embodiments, the JAK inhibitor is tofacitinib, baricitinib, or upadacitinib. In some embodiments, the DMARD is an anti-interleukin-6 (IL-6) agent. In some embodiments, the anti-IL-6 agent is tocilizumab. In some embodiments, the DMARD is an anti-CD20 agent. In some embodiments, the anti-CD20 agent is rituximab. In some embodiments, the DMARD is a T-cell costimulation inhibitor. In some embodiments, the T-cell costimulation inhibitor is abatacept. In some embodiments, the DMARD is an anti- inter leukin- 1 (IL-1) agent. In some embodiments, the anti- IL-1 agent is anakinra.
  • IL-1 inter leukin- 1
  • the subject has at least a 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, or 120% higher chance of achieving DAS28-CRP remission within 12 weeks of initiation of said administering compared to subjects having an ACPA level lower than the ACPA reference level prior to receiving an initial administration of the anti-FcRn agent.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 0.7 from baseline within 12 weeks of initiation of said administering. In some embodiments, the subject achieves DAS28-CRP remission within 12 weeks of initiation of said administering.
  • the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) in the subject by more than 10 from baseline within 12 weeks of initiation of said administering.
  • CD Al Clinical Disease Activity Index
  • the method provides a clinical benefit as measured by a decrease in Health Assessment Questionnaire-Disability Index (HAQ-DI) in the subject by more than 0.4 from baseline within 12 weeks of initiation of said administering.
  • HAQ-DI Health Assessment Questionnaire-Disability Index
  • the method further comprises administering at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD).
  • csDMARD conventional synthetic disease modifying anti-rheumatic drug
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 0.9 from baseline within 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks of initiation of said administering the at least one csDMARD. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28- CRP in the subject by more than 1.2 from baseline within 10 weeks, 11 weeks, or 12 weeks of initiation of said administering the at least one csDMARD. In some embodiments, the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) in the subject by more than 10 from baseline within 12 weeks of initiation of said administering the at least one csDMARD. In some embodiments, the csDMARD is methotrexate, hydroxychloroquine, leflunomide, or sulfasalazine.
  • the subject achieves an ACR50 response within 12 weeks of initiation of said administering.
  • the subject achieves an ACR70 response within 12 weeks of initiation of said administering.
  • the subject achieves an ACR90 response within 12 weeks of initiation of said administering.
  • the anti-FcRn agent is administered every week or every two weeks.
  • the anti-FcRn agent is administered intravenously or subcutaneously.
  • the anti-FcRn agent is administered at a therapeutically effective dose for a period sufficient to treat or reduce severity of rheumatoid arthritis in the subject.
  • the anti-FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, onlanolimab, SYNT002, ABY- 039, or DX-2507.
  • the anti-FcRn agent is an anti-FcRn antibody comprising: (a) a light chain, which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and (b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.
  • the light chain of the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 9; and (b) the heavy chain of the anti-FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 10.
  • the light chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 1; and (b) the heavy chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 2.
  • the anti-FcRn agent is Nipocalimab.
  • the anti-FcRn agent is administered intravenously at about 15 mg/kg to about 30 mg/kg based on the weight of the subject.
  • the method further comprises administering an anti-tumor necrosis factor (TNF) agent to the subject.
  • TNF anti-tumor necrosis factor
  • the subject demonstrated inadequate response to or is intolerant to a previous anti-TNF agent, which is different from the TNF agent administered to the subject.
  • the anti-FcRn agent is administered separately, simultaneously, or sequentially with the anti-TNF agent.
  • the anti-FcRn agent is administered sequentially with the anti-TNF agent.
  • the anti-FcRn agent is administered simultaneously with the anti-TNF agent.
  • the anti-TNF agent is administered intravenously or subcutaneously.
  • the anti-TNF agent is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, every 6 weeks, or every 8 weeks.
  • the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • the anti-TNF agent is an anti-TNF antibody comprises: (a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 42, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 43, a CDR L3 comprising an amino acid sequence of SEQ ID NO: 44; and (b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 45, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 46, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 47.
  • the light chain of the anti-TNF antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48; and (b) the heavy chain of the anti-TNF antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 49.
  • the light chain of the anti-TNF antibody comprises an amin acid sequence of SEQ ID NO: 40; and (b) the heavy chain of the anti-TNF antibody comprises an amino acid sequence of SEQ ID NO: 41.
  • the anti- TNF agent is golimumab.
  • the anti-TNF agent is an anti-TNF antibody comprising (a) a light chain comprising an amino acid sequence of SEQ ID NO: 29; and (b) a heavy chain comprising an amino acid sequence of SEQ ID NO: 30.
  • the anti-TNF agent is certolizumab pegol.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 0.8, more than 1, more than 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2, more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than 3, more than 3.2, more than 3.4, more than 3.6, more than 3.8, more than 4, more than 4.2, more than 4.4, more than 4.6, more than 4.8, more than 5, more than 5.2, more than 5.4, more than 5.6, more than 5.8, or more than 6 from baseline within 12 weeks of initiation of said administering.
  • the subject achieved DAS28-CRP LDA within 12 weeks of initiation of said administering.
  • the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) by more than 11, more than 13, more than 15, more than 17, more than 19, more than 21, more than 23, more than 25, more than 27, more than 29, more than 31, more than 33, more than 35, more than 37, more than 39, more than 41, more than 43, more than 45, more than 47, more than 49, more than 51, more than 53, more than 55, more than 57, more than 59, more than 61, more than 63, more than 65, more than 67, more than 69, or more than 70 from baseline within 12 weeks of initiation of said administering.
  • CD Al Clinical Disease Activity Index
  • the method provides a clinical benefit as measured by a decrease in Health Assessment Questionnaire-Disability Index (HAQ- DI) by more than 0.5, more than 0.6, more than 0.7, more than 0.8, more than 0.9 more than 1, more than 1.1, more than 1.2, more than 1.3, more than 1.4, more than 1.5, more than 1.6, more than 1.7, more than 1.8, more than 1.9, or more than 2 from baseline within 12 weeks of initiation of said administering.
  • HAQ- DI Health Assessment Questionnaire-Disability Index
  • an anti-FcRn agent for use in a method of treating or reducing severity of rheumatoid arthritis in a subject in need thereof, the method comprising administering the anti-FcRn agent to the subject, wherein, prior to the subject receiving an initial administration of the anti-FcRn agent, an anti-cyclic citrullinated peptide autoantibody (ACPA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level.
  • ACPA anti-cyclic citrullinated peptide autoantibody
  • an anti-FcRn agent for use in a method of treating or reducing severity of rheumatoid arthritis in a subject in need thereof, the method comprising (a) determining an ACPA level in a blood sample from the subject; and (b) administering an anti- neonatal Fc receptor (FcRn) agent to the subject if the ACPA level determined in step (a) is higher than an ACPA reference level.
  • FcRn anti- neonatal Fc receptor
  • the blood sample is serum sample.
  • the ACPA reference level is within a range from about 100- 1000 U/ml.
  • the ACPA reference level is about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or 1000 U/ml. In some embodiments, the ACPA reference level is within a range from about 400-600
  • the ACPA level in the blood sample is determined using an ELISA assay.
  • the ACPA level in the blood sample is determined using a cyclic citrullinated peptides (CCP) assay.
  • CCP cyclic citrullinated peptides
  • the ACPA level in the blood sample is determined using a CCP2 assay.
  • the ACPA level in the blood sample is determined using a CCP3 assay.
  • the subject has not been previously treated with a diseasemodifying antirheumatic drug (DMARD). In some embodiments, the subject demonstrated inadequate response to or is intolerant to at least one disease-modifying antirheumatic drug (DMARD).
  • the DMARD is an anti-tumor necrosis factor (TNF) agent.
  • the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab. In some embodiments, the anti-TNF agent is adalimumab, etanercept, golimumab, or infliximab.
  • the DMARD is a JAK inhibitor. In some embodiments, the JAK inhibitor is tofacitinib, baricitinib, or upadacitinib. In some embodiments, the DMARD is an anti-interleukin-6 (IL-6) agent. In some embodiments, the anti-IL-6 agent is tocilizumab. In some embodiments, the DMARD is an anti-CD20 agent. In some embodiments, the anti-CD20 agent is rituximab. In some embodiments, the DMARD is a T-cell costimulation inhibitor. In some embodiments, the T-cell costimulation inhibitor is abatacept. In some embodiments, the DMARD is an anti- inter leukin- 1 (IL-1) agent. In some embodiments, the anti- IL-1 agent is anakinra.
  • IL-1 inter leukin- 1
  • the subject has at least a 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, or 120% higher chance of achieving DAS28-CRP remission in the subject.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 0.7 from baseline within 12 weeks of initiation of said administering.
  • the subject achieves DAS28-CRP remission within 12 weeks of initiation of said administering.
  • the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) in the subject by more than 10 from baseline within 12 weeks of initiation of said administering.
  • CD Al Clinical Disease Activity Index
  • the method provides a clinical benefit as measured by a decrease in Health Assessment Questionnaire-Disability Index (HAQ-DI) in the subject by more than 0.4 from baseline within 12 weeks of initiation of said administering.
  • HAQ-DI Health Assessment Questionnaire-Disability Index
  • the method further comprises administering at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD).
  • csDMARD conventional synthetic disease modifying anti-rheumatic drug
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 0.9 from baseline within 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks of initiation of said administering the at least one csDMARD.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 1.2 from baseline within 10 weeks, 11 weeks, or 12 weeks of initiation of said administering the at least one csDMARD.
  • the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) in the subject by more than 10 from baseline within 12 weeks of initiation of said administering the at least one csDMARD.
  • the csDMARD is methotrexate, hydroxychloroquine, leflunomide, or sulfasalazine.
  • the subject achieves an ACR50 response within 12 weeks of initiation of said administering.
  • the subject achieves an ACR70 response within 12 weeks of initiation of said administering. In some embodiments, the subject achieves an ACR90 response within 12 weeks of initiation of said administering.
  • the anti-FcRn agent is administered every week or every two weeks.
  • the anti-FcRn agent is administered intravenously or subcutaneously.
  • the anti-FcRn agent is administered at a therapeutically effective dose.
  • the anti-FcRn agent is administered at a therapeutically effective dose for a period sufficient to treat or reduce severity of rheumatoid arthritis in the subject.
  • the anti-FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, onlanolimab, SYNT002, ABY- 039, or DX-2507.
  • the anti-FcRn agent is an anti-FcRn antibody comprising: (a) a light chain, which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and (b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.
  • the light chain of the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 9; and (b) the heavy chain of the anti-FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 10.
  • the light chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 1; and (b) the heavy chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 2.
  • anti-FcRn agent for use according to any one of claims 66-111 , wherein the anti- FcRn agent is nipocalimab.
  • the anti-FcRn agent is administered intravenously at about 15 mg/kg to about 30 mg/kg based on the weight of the subject.
  • the method further comprises administering an anti-tumor necrosis factor (TNF) agent to the subject.
  • TNF anti-tumor necrosis factor
  • the subject demonstrated inadequate response to or is intolerant to a previous anti-TNF agent, which is different from the TNF agent administered to the subject.
  • the anti-FcRn agent is administered separately, simultaneously, or sequentially with the anti-TNF agent.
  • the anti-FcRn agent is administered sequentially with the anti-TNF agent.
  • the anti-FcRn agent is administered simultaneously with the anti-TNF agent.
  • the anti-TNF agent is administered intravenously or subcutaneously.
  • the anti-TNF agent is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, every 6 weeks, or every 8 weeks.
  • the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • the anti-TNF agent is an anti-TNF antibody comprises: (a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 42, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 43, a CDR L3 comprising an amino acid sequence of SEQ ID NO: 44; and (b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 45, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 46, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 47.
  • the light chain of the anti-TNF antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48; and (b) the heavy chain of the anti-TNF antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 49.
  • the light chain of the anti-TNF antibody comprises an amin acid sequence of SEQ ID NO: 40; and (b) the heavy chain of the anti-TNF antibody comprises an amino acid sequence of SEQ ID NO: 41.
  • the anti-TNF agent is golimumab.
  • the anti-TNF agent is an anti-TNF antibody comprising (a) a light chain comprising an amino acid sequence of SEQ ID NO: 29; and (b) a heavy chain comprising an amino acid sequence of SEQ ID NO: 30.
  • the anti-TNF agent is certolizumab pegol.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 0.8, more than 1, more than 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2, more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than 3, more than 3.2, more than 3.4, more than 3.6, more than 3.8, more than 4, more than 4.2, more than 4.4, more than 4.6, more than 4.8, more than 5, more than 5.2, more than 5.4, more than 5.6, more than 5.8, or more than 6 from baseline within 12 weeks of initiation of said administering.
  • the subject achieves DAS28-CRP LDA within 12 weeks of initiation of said administering.
  • the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) by more than 11, by more than 13, more than 15, more than 17, more than 19, more than 21, more than 23, more than 25, more than 27, more than 29, more than 31, more than 33, more than 35, more than 37, more than 39, more than 41, more than 43, more than 45, more than 47, more than 49, more than 51, more than 53, more than 55, more than 57, more than 59, more than 61, more than 63, more than 65, more than 67, more than 69, or more than 70 from baseline within 12 weeks of initiation of said administering.
  • CD Al Clinical Disease Activity Index
  • the method provides a clinical benefit as measured by a decrease in Health Assessment Questionnaire-Disability Index (HAQ-DI) by more than 0.4, more than 0.5, more than 0.6, more than 0.7, more than 0.8, more than 0.9 more than 1, more than 1.1, more than 1.2, more than 1.3, more than 1.4, more than 1.5, more than 1.6, more than 1.7, more than 1.8, more than 1.9, or more than 2 from baseline within 12 weeks of initiation of said administering.
  • HAQ-DI Health Assessment Questionnaire-Disability Index
  • kits comprising an anti-neonatal Fc receptor (FcRn) agent and an anti -tumor necrosis factor (TNF) agent to the subject.
  • FcRn anti-neonatal Fc receptor
  • TNF anti -tumor necrosis factor
  • the components of the kit are disposed separately.
  • the anti-FcRn agent and the anti-TNF agent are for separate, simultaneous or sequential administration.
  • the anti-FcRn agent is an anti-FcRn agent as defined in any one of claims 43-47. In some embodiments, the anti-TNF agent is an anti-TNF agent as defined in any one of claims 56-61.
  • the kit further comprises instructions for use.
  • the kit further comprises instructions for a method of treating or reducing severity of rheumatoid arthritis in a subject.
  • the method is a method as defined above.
  • FIG. 1 depicts a schematic overview of a clinical trial study to evaluate the efficacy and safety of anti-FcRn antibodies for treatment of rheumatoid arthritis.
  • FIGs. 2A-2C are graphs showing changes in pharmacodynamic biomarkers.
  • FIG. 2A depicts percent change in IgG levels.
  • FIG. 2B depicts percent change in circulating immune complex (CIC) levels.
  • FIG. 2C depicts percent change in anti-cyclic citrullinated peptide antibody (anti-CCP antibody, also known as anti-citrullinated protein antibodies (ACPA)) levels. Values after treatment failure reported as missing; for change in anti-CCP analyses, patients with baseline anti-CCP below lower limit of quantitation excluded.
  • FIG. 3 depicts a schematic overview of a clinical trial study to evaluate the efficacy and safety of a combination of anti-FcRn antibodies and anti-TNF antibodies for treatment of rheumatoid arthritis.
  • FIG. 4 is a chart showing proportions of patients achieving DAS28-CRP remission at weekl2 among patients in nipocalimab group, patients in placebo group, patients in nipocalimab group and having baseline ACPA above median, and patients in placebo group and having baseline ACPA above median.
  • FIG. 5 is a chart showing proportions of patients achieving ACR50 response at week 12 among patients in nipocalimab group, patients in placebo group, patients in nipocalimab group and having baseline ACPA above median, and patients in placebo group and having baseline ACPA above median.
  • the present disclosure provides for embodiments for methods of treating or reducing the severity of rheumatoid arthritis (RA) and related symptoms or pathologies associated with the same.
  • the methods of treating or reducing severity of rheumatoid arthritis in a subject in need thereof comprises administering an agent against human neonatal Fc receptor (FcRn) to the subject.
  • FcRn human neonatal Fc receptor
  • an anti-citrullinated protein antibody (ACPA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level.
  • ACPA anti-citrullinated protein antibody
  • Anti -FcRn agents are useful, for example, to promote clearance of autoantibodies in a subject, to suppress antigen presentation in a subject, to block an immune response, such as blocking an immune complex- based activation of the immune response in a subject, or to treat immunological diseases (e.g., autoimmune diseases) in a subject.
  • the anti- FcRn agent is an anti-FcRn antibody.
  • antibody herein is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), scFV, nanobodies, VHH, and antibody fragments so long as they exhibit FcRn antigen-binding activity.
  • antibody or antibody molecule refers to a polypeptide, e.g., an immunoglobulin chain or fragment thereof, comprising at least one functional immunoglobulin variable domain sequence.
  • An antibody molecule encompasses antibodies (e.g., full-length antibodies) and antibody fragments.
  • an antibody molecule comprises an antigen binding or functional fragment of a full-length antibody, or a full-length immunoglobulin chain.
  • a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that is naturally occurring or formed by normal immunoglobulin gene fragment recombinatorial processes).
  • an antibody molecule refers to an immunologically active, antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment.
  • An antibody fragment e.g., functional fragment, comprises a portion of an antibody, e.g., Fab, Fab', F(ab')2, F(ab)2, variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv).
  • a functional antibody fragment binds to the same antigen as that recognized by the intact (e.g., full-length) antibody.
  • antibody fragment or “functional fragment” also include isolated fragments consisting of the variable regions, such as the “Fv” fragments consisting of the variable regions of the heavy and light chains or recombinant single chain polypeptide molecules in which light and heavy variable regions are connected by a peptide linker (“scFv proteins”).
  • an antibody fragment does not include portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues.
  • Exemplary antibody molecules include full length antibodies and antibody fragments, e.g., dAb (domain antibody), single chain, Fab, Fab’, and F(ab’)2 fragments, and single chain variable fragments (scFvs).
  • Immunoglobulin chains exhibit the same general structure of relatively conserved framework regions (FR) joined by three hypervariable regions, also called complementarity determining regions or CDRs.
  • the CDRs from the two chains of each pair are aligned by the framework regions, enabling binding to a specific epitope.
  • FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 From N-terminus to C-terminus, both light and heavy chains comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4.
  • the assignment of amino acids to each domain is in accordance with the definitions of Kabat Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)), or Chothia & Lesk J. Mol. Biol.
  • the antibodies provided herein comprise the same FRs and different CDRs. In some embodiments, the antibodies provided herein comprise the same CDRs and different FRs.
  • mutations in the FR are in the heavy chain. In some embodiments, mutations in the FR are in the FR1 of the heavy chain. In some embodiments, mutations in the FR are in the FR2 of the heavy chain. In some embodiments, mutations in the FR are in the FR3 of the heavy chain. In some embodiments, mutations in the FR are in the FR4 of the heavy chain.
  • mutations in the FR are in the light chain. In some embodiments, mutations in the FR are in the FR1 of the light chain. In some embodiments, mutations in the FR are in the FR2 of the light chain. In some embodiments, mutations in the FR are in the FR3 of the light chain. In some embodiments, mutations in the FR are in the FR4 of the light chain. In some embodiments, mutations in the FR are in the heavy and light chains. In some embodiments, mutations in the FR are in any one or more of the FRs of the heavy and light chains.
  • antibody molecule also encompasses whole or antigen binding fragments of domain, or single domain, antibodies, which can also be referred to as “sdAb” or “VHH.” Domain antibodies comprise either VH or VL that can act as stand-alone, antibody fragments. Additionally, domain antibodies include heavy-chain-only antibodies (HCAbs). Domain antibodies also include a CH2 domain of an IgG as the base scaffold into which CDR loops are grafted. It can also be generally defined as a polypeptide or protein comprising an amino acid sequence that is comprised of four framework regions interrupted by three complementarity determining regions. This is represented as FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.
  • sdAbs can be produced in camelids such as llamas, but can also be synthetically generated using techniques that are well known in the art.
  • the numbering of the amino acid residues of a sdAb or polypeptide is according to the general numbering for VH domains given by Kabat et al. ("Sequence of proteins of immunological interest," US Public Health Services, NIH Bethesda, MD, Publication No. 91, which is hereby incorporated by reference in its entirety).
  • FR1 of a sdAb comprises the amino acid residues at positions 1-30
  • CDR1 of a sdAb comprises the amino acid residues at positions 31-36
  • FR2 of a sdAb comprises the amino acids at positions 36-49
  • CDR2 of a sdAb comprises the amino acid residues at positions 50-65
  • FR3 of a sdAb comprises the amino acid residues at positions 66- 94
  • CDR3 of a sdAb comprises the amino acid residues at positions 95-102
  • FR4 of a sdAb comprises the amino acid residues at positions 103-113.
  • Domain antibodies are also described in WO 2004/041862 and WO 2016/065323, each of which is hereby incorporated by reference in its entirety.
  • antibody molecules can be monospecific (e.g., monovalent or bivalent), bispecific (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, hexavalent), or with higher orders of specificity (e.g., tetraspecific) and/or higher orders of valency beyond hexavalency.
  • An antibody molecule can comprise a functional fragment of a light chain variable region and a functional fragment of a heavy chain variable region, or heavy and light chains may be fused together into a single polypeptide.
  • the term “fused” or “linked” when used in reference to a protein having different domains or heterologous sequences means that the protein domains are part of the same peptide chain that are connected to one another with either peptide bonds or other covalent bonding.
  • the domains or section can be linked or fused directly to one another, or another domain or peptide sequence can be between the two domains or sequences and such sequences would still be considered fused or linked to one another.
  • the various domains or proteins provided for herein are linked or fused directly to one another or a linker sequence(s), such as a glycine/serine, glycine/alanine linker or other types of peptide linkers generally known to link the two domains together.
  • Two peptide sequences are linked directly if they are directly connected to one another or indirectly if there is a linker or other structure that links the two regions.
  • a linker can be directly linked to two different peptide sequences or domains.
  • variable region and “variable domain” refer to the portions of the light and heavy chains of an antibody that include amino acid sequences of complementary determining regions (CDRs, e g., CDRL1, CDR L2, CDRL3, CDR H1, CDR H2, and CDR H3) and framework regions (FRs).
  • CDRs complementary determining regions
  • FRs framework regions
  • amino acid positions assigned to CDRs and FRs are defined according to Kabat (Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)).
  • the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a CDR (defined further herein) or FR (defined further herein) of the variable region.
  • a heavy chain variable region may include a single inserted residue (i.e., residue 52a according to Kabat) after residue 52 of CDRH2 and inserted residues (i.e., residues 82a, 82b, 82c, etc. according to Kabat) after residue 82 of heavy chain FR.
  • the Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence.
  • CDRs refer to the regions of an antibody variable domain or variable region which are hypervariable in sequence and/or form structurally defined loops.
  • a CDR is also known as a hypervariable region.
  • the light chain and heavy chain variable regions each have three CDRs.
  • the light chain variable region contains CDR LI, CDR L2, and CDR L3.
  • the heavy chain variable region contains CDR Hl, CDR H2, and CDR H3.
  • Each CDR may include amino acid residues from a complementarity determining region as defined by Kabat (i.e., about residues 24-34 (CDR LI), 50-56 (CDR L2) and 89-97 (CDRL3) in the light chain variable region and about residues 31-35 (CDR Hl), SO- 65 (CDR H2) and 95-102 (CDR H3) in the heavy chain variable region).
  • Kabat i.e., about residues 24-34 (CDR LI), 50-56 (CDR L2) and 89-97 (CDRL3) in the light chain variable region and about residues 31-35 (CDR Hl), SO- 65 (CDR H2) and 95-102 (CDR H3) in the heavy chain variable region.
  • FcRn refers to a neonatal Fc receptor that binds to the Fc region of an IgG antibody, e.g., an IgGl antibody.
  • An exemplary FcRn is human FcRn having UniProt ID No. P55899, which is hereby incorporated by reference in its entirety. Human FcRn is believed to be responsible for maintaining the half-life of IgG by binding and trafficking constitutively internalized IgG back to the cell surface for the recycling of IgG.
  • the anti -FcRn antibody comprises a heavy chain and a light chain. In some embodiments, the anti-FcRn antibody comprises variable domains of a heavy chain and a light chain in a scFv format. In some embodiments, the heavy and light chain are linked with a peptide linker, such a glycine/serine or glycine/alanine linker.
  • the anti-FcRn antibody is nipocalimab (nipo, also known as M281), a fully human, anti-FcRn antibody.
  • nipocalimab is described in U.S. Patent No. 10,676,526, which is incorporated herein by reference in its entirety.
  • nipocalimab comprises or consists of a light chain comprising or consisting of the sequence:
  • the antibody comprises or consists of: (a) a light chain sequence comprising or consisting of SEQ ID NO: 1 or a light chain sequence comprising or consisting of a sequence that is at least 95%, 96%, 97% 98%, 99% identical to SEQ ID NO: 1, wherein the CDRL1 comprises the sequence TGTGSDVGSYNLVS (SEQ ID NO: 3), the CDRL2 comprises the sequence GDSERPS (SEQ ID NO: 4), the CDRL3 comprises the sequence SSYAGSGIYV (SEQ ID NO: 5); and (b) a heavy chain sequence comprising or consisting of SEQ ID NO: 2 or a heavy chain sequence comprising or consisting of a sequence that is at least 95%, 96%, 97% 98%, or 99% identical to SEQ ID NO: 2, wherein the CDR Hl comprises the sequence TYAMG (SEQ ID NO: 6), the CDR H2 comprises the sequence SIGASGSQTRYADS (SEQ ID NO: 7), and the CDR H3 comprises the sequence
  • the antibody comprises a light chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99%, or 100% identical to: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGV SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVL (SEQ ID NO: 9).
  • the light chain variable region comprises a CDR LI having the sequence of SEQ ID NO: 3, a CDR L2 comprising the sequence of SEQ ID NO: 4, and a CDR L3 comprising the sequence of SEQ ID NO: 5.
  • the antibody comprises a heavy chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99%, or 100% identical to: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQT RYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSS (SEQ ID NO: 10).
  • the heavy chain variable region comprises a CDR Hl comprising the sequence of SEQ ID NO: 6, a CDR H2 comprising the sequence of SEQ ID NO: 7, and a CDRH3 comprising the sequence of SEQ ID NO: 8.
  • the anti-FcRn antibody is efgartigimod (also known as ARGX- 113), a modified human IgGl -derived Fc fragment that binds FcRn.
  • efgartigimod is described in U.S. Patent No. 10,316,073, which is incorporated herein by reference in its entirety.
  • efgartigimod comprises or consists of a first subunit comprising or consisting of the sequence:
  • the anti-FcRn antibody is rozanolixizumab (also known as UCB7665), a humanized anti-FcRn antibody.
  • rozanolixizumab is described in U.S. Patent No. 10,233,243, which is incorporated herein by reference in its entirety.
  • rozanolixizumab comprises or consists of a light chain comprising or consisting of the sequence:
  • the anti-FcRn antibody is batoclimab (also known as IMVT-1401, RVT1401, HL161BKN, and HBM9161), a fully human, anti-FcRn antibody.
  • batoclimab is described in U.S. Patent No. 10,544,226, which is incorporated herein by reference in its entirety.
  • batoclimab comprises or consists of a light chain comprising or consisting of the sequence:
  • the anti-FcRn antibody is IMVT-1402 (also known as HL161ANS), a fully human, anti-FcRn antibody.
  • the anti-FcRn antibody is orilanolimab (also known as ALXN1830 and SYNT001), a humanized anti-FcRn antibody.
  • orilanolimab is described in U.S. Patent No. 10,626,175, which is incorporated herein by reference in its entirety.
  • orilanolimab comprises or consists of a light chain variable region comprising or consisting of the sequence:
  • the anti-FcRn antibody is SYNT002, a humanized anti-FcRn antibody.
  • SYNT002 is described in U.S. Patent No. 10,822,417, which is incorporated herein by reference in its entirety.
  • SYNT002 comprises or consists of a light chain variable region comprising or consisting of the sequence:
  • DIVMTQSPDSLSASVGDRVTITCKASQSVSNDVAWYQQKPGQPPKLLIYYASNRYTGVP DRFSGSGYGTDFTLTISSLQAEDVAVYFCQQDYSSLTFGQGTKLEIK (SEQ ID NO: 21); and a heavy chain variable region comprising or consisting of the sequence:
  • the anti-FcRn antibody is ABY-039 (also known as Affibody AB), a bivalent antibody-mimetic targeting FcRn.
  • ABY-039 is described in U.S. Patent No. 10,323,066, which is incorporated herein by reference in its entirety.
  • the anti-FcRn antibody is DX-2507, a fully human anti-FcRn monoclonal antibody.
  • DX-2507 is described in U.S. Patent No. 9,862,768, which is incorporated herein by reference in its entirety.
  • DX- 2507 comprises or consists of a light chain comprising or consisting of the sequence:
  • the Fc domain of the antibody is not fucosy lated. In some embodiments of all the methods described herein, the Fc domain of the antibody is not glycosylated. In some embodiments of all the methods described herein, the antibody lacks effector function. In some embodiments of all the methods described herein, the antibody is an IgGl antibody.
  • antibodies described herein may comprise mutations (e.g., amino acid substitutions, additions, and/or deletions) outside of the CDRs (i.e., in framework regions (FRs)).
  • An amino acid substitution, addition, and/or deletion can be a substitution, addition, and/or deletion of one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more).
  • An amino acid substitution, addition, and/or deletion can be a substitution, addition, and/or deletion of eight or fewer, seven or fewer, six or fewer, five or fewer, four or fewer, three or fewer, or two or fewer single amino acids.
  • antibodies described herein may include amino acid substitutions, additions, and/or deletions in the constant regions (e.g., Fc region) of the antibody that, e.g., lead to decreased effector function, e.g., decreased complement-dependent cytolysis (CDC), antibody-dependent cell-mediated cytolysis (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and/or decreased B-cell killing.
  • the constant regions are not involved directly in binding an antibody to its target, but exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity.
  • the antibodies described herein are characterized by decreased binding (or in some cases absence of binding) to human complement factor Clq and/or human Fc receptor on natural killer (NK) cells. In other embodiments, the antibodies are characterized by decreased binding (or in some cases absence of binding) to human FcyRI, FcyRIIA, and/or FcyRIIIA.
  • anti- FcRn antibodies described herein contain asparagine (N) at position 297 (numbering according to the EU System). In some embodiments, anti-FcRn antibodies described herein are aglycosylated at position 297 (numbering according to the EU System).
  • anti-FcRn antibodies described herein do not have an N at position 297 (EU numbering) in any one of SEQ ID NOs: 2 and 23-26, such that the antibody is aglycosylated at that position.
  • the resulting effectorless antibody shows very little binding to complement or Fc receptors (i.e., complement Clq binding), indicating low CDC potential.
  • the Fc region is an effectorless Fc region.
  • the heavy chain of the antibody comprises a sequence having no more than 5, 4, 3, 2, or 1 single amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 2.
  • the light chain of the isolated antibody comprises a sequence having no more than 5, 4, 3, 2 or 1 single amino acid substitutions relative to the sequence of SEQ ID NO: 1.
  • percent (%) identity refers to the percentage of amino acid (or nucleic acid) residues of a candidate sequence, e.g., an anti-FcRn antibody of the present disclosure, that are identical to the amino acid (or nucleic acid) residues of a reference sequence, e.g., a wild-type anti-FcRn antibody, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity (i.e., gaps can be introduced in one or both of the candidate and reference sequences for optimal alignment and non-homologous sequences can be disregarded for comparison purposes).
  • the percent amino acid (or nucleic acid) sequence identity of a given candidate sequence to, with, or against a given reference sequence is calculated as follows:
  • A is the number of amino acid (or nucleic acid) residues scored as identical in the alignment of the candidate sequence and the reference sequence
  • B is the total number of amino acid (or nucleic acid) residues in the reference sequence.
  • the percent amino acid (or nucleic acid) sequence identity of the candidate sequence to the reference sequence would not equal to the percent amino acid (or nucleic acid) sequence identity of the reference sequence to the candidate sequence.
  • a reference sequence aligned for comparison with a candidate sequence may show that the candidate sequence exhibits from 50% to 100% identity across the full length of the candidate sequence or a selected portion of contiguous amino acid (or nucleic acid) residues of the candidate sequence.
  • the length of the candidate sequence aligned for comparison purpose is at least 30%, e.g., at least 40%, e.g., at least 50%, 60%, 70%, 80%, 90%, or 100% of the length of the reference sequence.
  • a substitution, deletion, or insertion may comprise a certain number of amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more).
  • substitution, deletion, or insertion comprises, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or n amino acids.
  • the number or substitutions, deletions, or insertions can comprise a percent of the total sequence (e.g., 1%, 5%, 10%, 15%, 20%, or more) where the number of substitutions, deletions, or insertions alters 5%, 10%, 15%, 20% or more, of the amino acids in the total sequence.
  • Anti-FcRn is a novel mechanism that has never been tested in rheumatoid arthritis patients. The mechanism is different from all existing standard of care (SOCs), and therefore what we know for the existing SOCs cannot be directly extrapolated to anti-FcRn.
  • SOCs standard of care
  • the inventors defined specific and novel ACPA baseline thresholds that are not just positive/negative, which has not been disclosed for other mechanisms of actions.
  • the ACPA reference level used herein is within a range from about 100-1000 U/ml.
  • the ACPA reference level is within a range from about 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-170, 170-180, 180-190, 190- 200, 200-210, 210-220, 220-230, 230-240, 240-250, 250-260, 260-270, 270-280, 280-290, 290-
  • the ACPA reference level used herein is within a range from about 400-600 U/ml. In some embodiments, the ACPA reference level is about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or 1000 U/ml. In a preferred embodiment, the ACPA reference level is within a range from about 400-600 U/ml.
  • ACPA level can be determined using blood sample from the subject/patient. Over the years, various assays for determining ACPA levels have been developed. Any known or yet to be developed assays can be used herein to determine the ACPA level for the subject/patient. For example, the ACPA level can be determined using an ELISA assay, such as a cyclic citrullinated peptides (CCP) assay. Currently, three (3) generation of CCP assay have been developed, CCP1, CCP2, and CCP3.
  • CCP cyclic citrullinated peptides
  • Exemplary assays useful herein for determining ACAP level in subjects/patients include, without limitation, Diastat (manufactured by Axis-Shield Diagnostics, Scotland, UK), CCPoint (manufactured by Eurodiagnostica, Netherlands), CCPlus (manufactured by Eurodiagnostica, Netherlands), EDIA (manufactured by Eurodiagnostica, Netherlands), RA anti-CCP ELISA (manufactured by Eurodiagnostica, Netherlands), Euroimmun (manufactured by Euroimmun, Germany), Quanta Lite (manufactured by Inova, United States), ELIA CCP (manufactured by Phadia, Sweden, Germany), Quanta Lite CCP3 (manufactured by Inova, United States), Quanta Lite CCP3.1 (manufactured by Inova, United States), Org 548 anti-MCV (manufactured by Orgentec, Germany), Immunoscan-CCP PlusTM (manufactured by from Eurodiag
  • the method disclosed herein comprises administering an anti- FcRn antibody to the subject with rheumatoid arthritis, wherein the subject has a baseline ACPA level higher than an ACPA reference level that is within the range of about 400-600 U/ml.
  • the method disclosed herein comprises administering an anti-FcRn antibody to the subject with rheumatoid arthritis, wherein the subject has a baseline ACPA level higher than an ACPA reference level that is within the range of about 400-600 U/ml, and wherein the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • baseline ACPA level used herein refers to the ACPA level of a subject/patient that is or has been determined prior to receiving a first or initial administration of the anti-FcRn agent.
  • the method disclosed herein for treating or reducing severity of rheumatoid arthritis in a subject in need thereof comprises administering an anti-neonatal Fc receptor (FcRn) agent to the subject, wherein, prior to the subject receiving an initial administration of the anti-FcRn agent, an anti-citrullinated protein antibody (ACPA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level.
  • the anti-FcRn agent may be an anti-FcRn antibody.
  • the ACPA reference level is about 100 U/ml
  • the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 125 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 150 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 175 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 200 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 225 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 250 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 275 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 300 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 325 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 350 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 375 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 400 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 425 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 450 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 475 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 500 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 525 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 550 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 575 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 600 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 625 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 650 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 675 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 700 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 725 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 750 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 775 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 800 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 825 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 850 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 875 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 900 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 925 U/ml and the anti- FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 950 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 975 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level may be about 1000 U/ml and the anti-FcRn agent may comprise a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the ACPA reference level is about 100 U/ml, and the anti-FcRn agent is nipocalimab.
  • the ACPA reference level may be about 125 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 150 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 175 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 200 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 225 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 250 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 275 U/ml and the anti- FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 300 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 325 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 350 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 375 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 400 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 425 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 450 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 475 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 500 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 525 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 550 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 575 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 600 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 625 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 650 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 675 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 700 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 725 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may about be 750 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 800 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 825 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 850 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 875 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 900 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 925 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 950 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 975 U/ml and the anti-FcRn agent may be nipocalimab.
  • the ACPA reference level may be about 1000 U/ml and the anti-FcRn agent may be nipocalimab.
  • the subject being administered the anti-FcRn agent has demonstrated inadequate response to or is intolerant to at least one disease-modifying antirheumatic drug (DMARD).
  • DMARD disease-modifying antirheumatic drug
  • IR inadequate response
  • An inadequate response can be measured by clinical, laboratory or other measures of disease activity, including symptoms thereof.
  • the lack of sufficient response to a treatment of a disease can be defined by specific clinical or other endpoints, including for example, where no discernable response to the treatment is observed after being treated for a sufficient period of time, or where a response to the treatment is observed, but considered insufficient to meaningfully alleviate symptoms of the disease.
  • the response or efficacy of a treatment to RA can be evaluated, for example, by Disease Activity Index Score 28 using C-reactive protein (CRP) (DAS28-CRP), DAS28-ESR, DAS28 LDA, DAS28-CRP remission, ACR responses, CD Al, SDAI, ACR/EULAR remission.
  • CRP C-reactive protein
  • DAS28-CRP C-reactive protein
  • ESR C-reactive protein
  • DAS28 LDA DAS28 LDA
  • DAS28-CRP remission ACR responses
  • CD Al CD Al
  • SDAI ACR/EULAR remission
  • the efficacy can also be measured by the Physician’s Global Assessment (PGA) of disease activity, joint assessment (tenderness and swelling), duration of morning stiffness.
  • PGA Global Assessment
  • the efficacy can further be assessed by health-related quality of life outcomes, pain, and fatigue, e.g., PtGA of disease activity, pain VAS, FACIT-Fatigue, Joint Pain Severity NRS, HAQ-DI, SF-36 version 2 Standard survey.
  • PtGA of disease activity e.g., pain VAS, FACIT-Fatigue, Joint Pain Severity NRS, HAQ-DI, SF-36 version 2 Standard survey.
  • a subject has demonstrated IR to >1 anti-TNF agent, as assessed by the treating physician: a) After at least 12 weeks dosage of etanercept, adalimumab, golimumab, and/or b. After at least 14 weeks dosage (i.e., at least 4 doses) of infliximab.
  • a subject has demonstrated IR to at least one biological disease-modifying antirheumatic drug (bDMARD) other than anti-TNF agents, as assessed by the treating physician, after at least 12 weeks of therapy including but not limited to abatacept, anakinra, tocilizumab, and sarilumab or at least 16 weeks of therapy with rituximab.
  • bDMARD biological disease-modifying antirheumatic drug
  • a subject has demonstrated IR to bDMARD other than anti-TNF agent, as assessed by the treating physician.
  • a subject has demonstrated IR to at least one JAKi agent, as assessed by the treating physician, after at least 12 weeks of therapy with a JAKi which includes but is not limited to tofacitinib, baricitinib, upadacitinib.
  • “intolerant to a therapy” refers to not being able to be treated with the therapy without inducing serious adverse event (SAE) or serious adverse effect.
  • SAE serious adverse event
  • the phrases “serious adverse event (SAE)” and “serious adverse effect” mean any adverse event that is serious, as defined by the Food and Drug Administration (FDA) Code of Federal Regulations (CFR), Chapter 21.
  • a SAE can be any AE or suspected adverse reaction that in the view of an investigator or a medical doctor, results in any of the following outcomes: death, a life threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
  • Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in the above definition.
  • the DMARD is an anti-tumor necrosis factor (TNF) agent.
  • the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • the DMARD is a JAK inhibitor.
  • JAK inhibitor is tofacitinib, baricitinib, or upadacitinib.
  • the DMARD is an anti-interleukin-6 (IL-6) agent.
  • the anti-IL-6 agent is tocilizumab.
  • the DMARD is an anti-CD20 agent.
  • the anti-CD20 agent is rituximab.
  • the DMARD is a T-cell costimulation inhibitor.
  • the T-cell costimulation inhibitor is abatacept.
  • the DMARD is an anti- Inter leukin- 1 (IL-1) agent.
  • the anti- IL-1 agent is anakinra.
  • the anti-TNF agent is adalimumab (also known as HUMIRA®), a human anti-TNF a monoclonal antibody.
  • adalimumab is described in U.S. Patent No. 6,090,382 as D2E7, which is incorporated herein by reference in its entirety.
  • adalimumab comprises or consists of a light chain comprising or consisting of the sequence:
  • the anti-TNF agent is certolizumab pegol (also known as CIMZIA®), a PEGylated Fab fragment.
  • certolizumab pegol is described in U.S. Patent No. 7,012,135, which is incorporated herein by reference in its entirety.
  • certolizumab pegol comprises or consists of a light chain comprising or consisting of the sequence:
  • the anti-TNF agent is etanercept (also known as ENBRELTM), a TNFR-Ig Fc fusion protein.
  • etanercept also known as ENBRELTM
  • ENBRELTM ENBRELTM
  • etanercept is described in U.S. Patent Nos. 5,395,760, and 5,605,690, which are incorporated herein by reference in their entireties.
  • etanercept comprises or consists of the sequence:
  • the anti-TNF agent is golimumab (also known as SIMPONI®), a human anti-TNF a monoclonal antibody.
  • golimumab is described in U.S. Patent No. 7,250,165, which is incorporated herein by reference in its entirety.
  • golimumab comprises or consists of a light chain comprising or consisting of the sequence:
  • the antibody has: (a) a light chain sequence that is at least 95%, 96%, 97% 98%, or 99% identical to SEQ ID NO: 40, wherein the CDR LI comprises the sequence RASQSVYSYLA (SEQ ID NO: 42), the CDR L2 comprises the sequence DASNRAT (SEQ ID NO: 43), the CDR L3 comprises the sequence QQRSNWPPFT (SEQ ID NO: 44); and (b) a heavy chain sequence that is at least 95%, 96%, 97% 98%, or 99% identical to SEQ ID NO: 41, wherein the CDR Hl comprises the sequence SYAMH (SEQ ID NO: 45), the CDR H2 comprises the sequence FMSYDGSNKKYADSVKG (SEQ ID NO: 46), and the CDR H3 comprises the sequence DRGIAAGGNYYYYGMDV (SEQ ID NO: 47).
  • the antibody comprises a light chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99%, or 100% identical to: EIVLTQSPAT LSLSPGERATLSCRASQSVYSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD FTLTISSLEPEDFAVYYCQQRSNWPPFTFGPGTKVDIKRTV (SEQ ID NO: 48).
  • the light chain variable region contains a CDR LI having the sequence of SEQ ID NO: 42, a CDRL2 having the sequence of SEQ ID NO: 43, a CDRL3 having the sequence of SEQ ID NO: 44.
  • the antibody comprises a heavy chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99%, or 100% identical to: QVQLVESGGG WQPGRSLRLSCAASGFIFSSYAMHWVRQAPGNGLEWVAFMSYDGSNKKYADSVKGR FTISRDNSKNTLYLQMNSLRAEDTAVYYCARDRGIAAGGNYYYYGMDVWGQGTTVTV SS (SEQ ID NO: 49).
  • the heavy chain variable region contains a CDR Hl having the sequence of SEQ ID NO: 45, a CDR H2 having the sequence of SEQ ID NO: 46, and a CDRH3 having the sequence of SEQ ID NO: 47.
  • the anti-TNF agent is infliximab (also known as REMICADETM), a chimeric anti-TNFa monoclonal antibody.
  • infliximab is described in U.S. Patent No. 7,070,775, which is incorporated herein by reference in its entirety.
  • infliximab comprises or consists of a light chain comprising or consisting of the sequence:
  • the DMARD is an anti-TNF agent.
  • the method comprises administering an anti-FcRn antibody to a subject with rheumatoid arthritis, wherein the subject i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to the DMARD that is an anti-TNF agent, and wherein the anti-FcRn antibody comprising a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the method comprises administering an anti-FcRn antibody to a subject with rheumatoid arthritis, wherein the subject i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to the DMARD that is an anti-TNF antibody, and wherein the anti-FcRn antibody comprising a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2.
  • the subject with rheumatoid arthritis is also treated with an anti- TNF agent, as described above.
  • the anti-TNF agent that is administered to the subject may be different to the anti-TNF agent which the subject has demonstrated inadequate response to or is/was intolerant to.
  • the anti-TNF agent is an anti-TNF antibody, as described above.
  • the anti-FcRn agent and the anti-TNF agent are administered separately, simultaneously, or sequentially.
  • an anti- FcRn antibody and an anti-TNF antibody are administered to a subject with rheumatoid arthritis separately, simultaneously, or sequentially.
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, wherein the subject is being administered an anti-FcRn agent and an anti-TNF agent separately, simultaneously, or sequentially.
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, wherein the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially.
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, wherein the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially, and wherein the DMARD is the same as the anti-TNF antibody that is being administered.
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, wherein the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially, and wherein the DMARD is different from the anti-TNF antibody that is being administered.
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, and the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially, wherein the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2 and the anti-TNF antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 29 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 30.
  • the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, and the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially, wherein the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2 and the anti-TNF antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 29 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 30, and wherein the DMARD is different from the anti-TNF antibody that is being administered.
  • the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO:
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, and the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially, wherein the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2 and the anti-TNF antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 40 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 41.
  • the subject with rheumatoid arthritis i) has a baseline ACPA level higher than an ACPA reference level that is within the range from about 400-600 U/ml and ii) has demonstrated inadequate response or is intolerant to a DMARD, and the subject is being administered an anti-FcRn antibody and an anti-TNF antibody separately, simultaneously, or sequentially, wherein the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 1 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 2 and the anti-TNF antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO: 40 and b) a heavy chain comprising or consisting of the sequence of SEQ ID NO: 41, and wherein the DMARD is different from the anti-TNF antibody that is being administered.
  • the anti-FcRn antibody comprises a) a light chain comprising or consisting of the sequence of SEQ ID NO
  • methods of the invention may comprise administering an anti-FcRn agent (such as an anti-FcRn antibody) to the subject, wherein, prior to the subject receiving an initial administration of the anti-FcRn agent, an anti-citrullinated protein antibody (APCA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level, and wherein the method further comprises administering an anti-tumor necrosis factor (TNF) agent to the subject.
  • the ACPA reference level is about 100 U/ml
  • the anti-TNF agent is golimumab.
  • the ACPA reference level may be about 125 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 150 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 175 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 200 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 225 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 250 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 275 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 300 U/ml and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 325 U/ml and the anti- agent may be golimumab.
  • the ACPA reference level may be about 350 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 375 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 400 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 425 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 450 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 475 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 500 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 525 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 550 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 575 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 600 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 625 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 650 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 675 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 700 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 725 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 750 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 800 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 825 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 850 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 875 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 900 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 925 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 950 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 975 U/ml and the antiagent may be golimumab.
  • the ACPA reference level may be about 1000 U/ml and the anti ⁇ agent may be golimumab.
  • the ACPA reference level is about 100 U/ml, the anti-FcRn agent is nipocalimab and the anti-TNF agent is golimumab.
  • the ACPA reference level may be about 125 U/ml, the anti-FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 150 U/ml, the anti-FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 175 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 200 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 225 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 250 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 275 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 300 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 325 U/ml , the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 350 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 375 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 400 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 425 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 450 U/ml , the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 475 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 500 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 525 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 550 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 575 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 600 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 625 U/ml , the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 650 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 675 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 700 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 725 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 750 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 775 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 800 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 825 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 850 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 875 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 900 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 925 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 950 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the ACPA reference level may be about 975 U/ml, the anti- FcRn agent may be nipocalimab and the anti-TNF agent may be golimumab.
  • the ACPA reference level may be about 1000 U/ml, the anti-FcRn agent may be nipocalimab and the anti- TNF agent may be golimumab.
  • the subject being administered the anti-FcRn agent also receives at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD) treatment.
  • the subject being administered the anti-FcRn agent and anti- TNF agent also receives at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD) treatment.
  • the csDMARD is methotrexate, hydroxychloroquine, leflunomide, or sulfasalazine.
  • the methods described herein comprise administering the anti- FcRn agent, and optionally, separately, simultaneously, or sequentially with the anti-TNF agent to the subject or patient.
  • the terms “subject” and “patient” can be used interchangeably.
  • the anti-FcRn agent and the anti-TNF agent are administered concurrently.
  • the anti-FcRn agent and the anti-TNF agent are administered sequentially.
  • the anti-FcRn agent is administered every week or every two weeks.
  • the anti-TNF agent is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, every 6 weeks, or every 8 weeks.
  • the anti-FcRn agent is administered every week, and the anti-TNF agent is administered every week. In some embodiments, the anti-FcRn agent is administered every week, and the anti-TNF agent is administered every 2 weeks. In some embodiments, the anti-FcRn agent is administered every week, and the anti-TNF agent is administered every 3 weeks. In some embodiments, the anti- FcRn agent is administered every week, and the anti-TNF agent is administered every 4 weeks. In some embodiments, the anti-FcRn agent is administered every two weeks, and the anti-TNF agent is administered every week. In some embodiments, the anti-FcRn agent is administered every two weeks, and the anti-TNF agent is administered every two weeks.
  • the anti-FcRn agent is administered every two weeks, and the anti-TNF agent is administered every 3 weeks. In some embodiments, the anti-FcRn agent is administered every two weeks, and the anti-TNF agent is administered every 4 weeks.
  • the anti-FcRn agent is nipocalimab and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is nipocalimab and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is nipocalimab and the anti- TNF agent is etanercept. In some embodiments, the anti-FcRn agent is nipocalimab and the anti- TNF agent is golimumab. In some embodiments, the anti-FcRn agent is nipocalimab and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is rozanolixizumab and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is rozanolixizumab and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is rozanolixizumab and the anti-TNF agent is etanercept. In some embodiments, the anti-FcRn agent is rozanolixizumab and the anti-TNF agent is golimumab. In some embodiments, the anti-FcRn agent is rozanolixizumab and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is batoclimab and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is batoclimab and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is batoclimab and the anti-TNF agent is etanercept. In some embodiments, the anti-FcRn agent is batoclimab and the anti-TNF agent is golimumab. In some embodiments, the anti-FcRn agent is batoclimab and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is IMVT-1402 and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is IMVT-1402 and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is IMVT-1402 and the anti- TNF agent is etanercept. In some embodiments, the anti-FcRn agent is IMVT-1402 and the anti- TNF agent is golimumab. In some embodiments, the anti-FcRn agent is IMVT-1402 and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is efgartigimod and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is efgartigimod and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is efgartigimod and the anti- TNF agent is etanercept. In some embodiments, the anti-FcRn agent is efgartigimod and the anti- TNF agent is golimumab. In some embodiments, the anti-FcRn agent is efgartigimod and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is orilanolimab and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is orilanolimab and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is orilanolimab and the anti- TNF agent is etanercept. In some embodiments, the anti-FcRn agent is orilanolimab and the anti- TNF agent is golimumab. In some embodiments, the anti-FcRn agent is orilanolimab and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is SYNT002 and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is SYNT002 and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is SYNT002 and the anti-TNF agent is etanercept. In some embodiments, the anti-FcRn agent is SYNT002 and the anti-TNF agent is golimumab. In some embodiments, the anti-FcRn agent is SYNT002 and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is ABY- 039 and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is ABY- 039 and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is ABY- 039 and the anti-TNF agent is etanercept. In some embodiments, the anti-FcRn agent is ABY- 039 and the anti-TNF agent is golimumab. In some embodiments, the anti-FcRn agent is ABY- 039 and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is DX-2507 and the anti-TNF agent is adalimumab. In some embodiments, the anti-FcRn agent is DX-2507 and the anti-TNF agent is certolizumab pegol. In some embodiments, the anti-FcRn agent is DX-2507 and the anti-TNF agent is etanercept. In some embodiments, the anti-FcRn agent is DX-2507 and the anti-TNF agent is golimumab. In some embodiments, the anti-FcRn agent is DX-2507 and the anti-TNF agent is infliximab.
  • the anti-FcRn agent is administered as part of a pharmaceutical composition.
  • the pharmaceutical composition comprises a therapeutically effective amount of the anti-FcRn agent.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered as a single dose.
  • dose refers to a single administration of the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent.
  • the anti-FcRn agent is dosed based on the weight of the subject. In some embodiments, the anti-FcRn agent is dosed at a fixed dose regardless the weight of the subject.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 5 mg/kg to about 60 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 5 mg/kg to about 15 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 15 mg/kg to about 30 mg/kg. In some embodiments, the anti- FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from, about 15 mg/kg to about 60 mg/kg.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 30 mg/kg to about 60 mg/kg. In some embodiments, the anti-FcRn agent is administered every week or every two weeks at the dose ranges above. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered intravenously or subcutaneously. In some embodiments, the anti-FcRn agent is nipocalimab.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 100 - 1000 mg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 200 - 8000 mg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose from about 300 - 700 mg. In some embodiments, the anti-FcRn agent is administered every week or every two weeks at the dose ranges above. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered subcutaneously. In some embodiments, the anti-FcRn agent is nipocalimab.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 60 mg/kg. In some embodiments, the anti- FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 55 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 50 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti- FcRn agent is administered at a dose of about 45 mg/kg.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 40 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 35 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 30 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 25 mg/kg.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 20 mg/kg. In some embodiments, the anti- FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 15 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered at a dose of about 10 mg/kg. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti- FcRn agent is administered at a dose of about 5 mg/kg.
  • the pharmaceutical composition comprises a therapeutically effective amount of the anti-FcRn agent.
  • the therapeutically effective amount is from about 5 mg/kg to about 60 mg/kg, about 5 mg/kg to about 15 mg/kg, about 15 mg/kg to about 30 mg/kg, about 15 mg/kg to about 45 mg/kg, about 30 mg/kg to about 45 mg/kg, or about 30 mg/kg to about 60 mg/kg of the anti-FcRn antibody (based on the weight of the subject).
  • the therapeutically effective amount is about 5 mg/kg, about 15 mg/kg, about 30 mg/kg, or about 45 mg/kg.
  • the therapeutically effective amount is about 5 mg/kg.
  • the therapeutically effective amount is about 15 mg/kg.
  • the therapeutically effective amount is about 30 mg/kg.
  • the therapeutically effective amount is about 45 mg/kg.
  • compositions comprising an anti-FcRn antibody are administered to a patient suffering from rheumatoid arthritis in a therapeutically effective amount from about 5 mg/kg to about 60 mg/kg (based on the weight of the subject) every 2 weeks.
  • pharmaceutical compositions comprising an anti-FcRn antibody are administered to a patient suffering from rheumatoid arthritis who previously received at least one DMARD in a therapeutically effective amount from about 5 mg/kg to about 60 mg/kg every 2 weeks.
  • the pharmaceutical composition is administered to the patient in a therapeutically effective amount from about 15 mg/kg to about 30 mg/kg every 2 weeks.
  • the pharmaceutical composition is administered to the patient in a therapeutically effective amount of about 15 mg/kg every 2 weeks. In some embodiments, the pharmaceutical composition is administered to the patient in a therapeutically effective amount of about 30 mg/kg every 2 weeks. In some embodiments, the pharmaceutical composition is administered to the patient in a therapeutically effective amount of about 45 mg/kg every 2 weeks. In some embodiments, the rheumatoid arthritis is moderate to severe active rheumatoid arthritis.
  • the anti-FcRn agent preferably an anti-FcRn antibody
  • the initial dose is different from every week or every two weeks dose.
  • the dose is the same every time it is administered.
  • the pharmaceutical composition is administered every week, every two weeks, or monthly.
  • the pharmaceutical composition is administered every week.
  • the pharmaceutical composition is administered every two weeks.
  • the pharmaceutical composition is administered monthly.
  • the anti-TNF agent preferably an anti-TNF antibody
  • the initial dose is different from every week or every two weeks dose.
  • the dose is the same every time it is administered.
  • the pharmaceutical composition is administered every week, every two weeks, or monthly.
  • the pharmaceutical composition is administered every week.
  • the pharmaceutical composition is administered every two weeks.
  • the pharmaceutical composition is administered every monthly.
  • the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered at a dose from about 50 - 500 mg. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered at a dose from about 10 - 100 mg. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered at a dose from about 20 - 200 mg. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered at a dose from about 20 - 50 mg. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered at a dose from about 30 - 150 mg.
  • the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered at a dose from about 40 - 100 mg. In some embodiments, the anti-TNF agent is administered every week, every two weeks, every three weeks, or every four weeks at the dose ranges above. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered intravenously or subcutaneously. In some embodiments, the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • the administration of the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent takes place over about 30-90 minutes. In some embodiments, the administration takes place over about 15-60 minutes. In some embodiments, the administration takes place in about 15 to about 30 minutes. In some embodiments, the administration takes place in about 15 to about 45 minutes. In some embodiments, the administration takes place in about 15 to about 90 minutes. In some embodiments, the administration takes place in about 15 to about 120 minutes. In some embodiments, the administration takes place in about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes.
  • the administration of the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent takes place over about 30-90 minutes. In some embodiments, the administration takes place over about 15-60 minutes. In some embodiments, the administration takes place in about 15 to about 30 minutes. In some embodiments, the administration takes place in about 15 to about 45 minutes. In some embodiments, the administration takes place in about 15 to about 90 minutes. In some embodiments, the administration takes place in about 15 to about 120 minutes. In some embodiments, the administration takes place in about 15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, or about 120 minutes.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered parenterally. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered intravenously or subcutaneously. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered intraperitoneal, intradermally, or intramuscularly. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered intravenously. In some embodiments, the anti- FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered subcutaneously.
  • the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered using an infusion pump. In some embodiments, the anti-FcRn agent or pharmaceutical composition comprising the anti-FcRn agent is administered using an autoinjector.
  • the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered parenterally. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered intravenously or subcutaneously. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered intraperitoneal, intradermally, or intramuscularly. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti- TNF agent is administered intravenously. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered subcutaneously. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered using an infusion pump. In some embodiments, the anti-TNF agent or pharmaceutical composition comprising the anti-TNF agent is administered using an auto injector.
  • any pharmaceutical composition described herein comprises one or more of sodium phosphate, sodium chloride, trehalose, or polysorbate.
  • the term “pharmaceutical composition” refers to a medicinal or pharmaceutical formulation that contains an active ingredient as well as one or more excipients and diluents to enable the active ingredient suitable for the method of administration.
  • the pharmaceutical composition of the present disclosure includes pharmaceutically acceptable components that are compatible with the anti-FcRn agent, the anti-TNF agent, or both.
  • the pharmaceutical composition may be in aqueous form for intravenous or subcutaneous administration or in tablet or capsule form for oral administration.
  • the composition is suitable for intravenous administration.
  • the composition is suitable for subcutaneous administration.
  • the pharmaceutical compositions that contain an anti-TNF agent may be formulated for intravenous administration, parenteral administration, subcutaneous administration, intramuscular administration, intra-arterial administration, intrathecal administration, or intraperitoneal administration.
  • the pharmaceutical composition may also be formulated for, or administered via, oral, nasal, spray, aerosol, rectal, or vaginal administration.
  • various effective pharmaceutical carriers are known in the art.
  • the term “pharmaceutically acceptable carrier” refers to an excipient or diluent in a pharmaceutical composition.
  • the pharmaceutically acceptable carrier must be compatible with the other ingredients of the formulation and not deleterious to the recipient.
  • the pharmaceutically acceptable carrier must provide adequate pharmaceutical stability to the Fc construct.
  • the nature of the carrier differs with the mode of administration. For example, for intravenous administration, an aqueous solution carrier is generally used; for oral administration, a solid carrier may be preferred.
  • the term “therapeutically effective amount” refers to an amount, e.g., pharmaceutical dose, effective in inducing a desired biological effect in a subject or patient or in treating a patient having a condition or disorder described herein. It is also to be understood that a “therapeutically effective amount” may be interpreted as an amount giving a desired therapeutic effect, either taken in one dose or in any dosage or route, taken alone or in combination with other therapeutic agents.
  • the term “no more than” refers to an amount that is less than or equal to. This may be an amount in integers. For example, no more than two substitutions can refer to 0, 1, or 2 substitutions.
  • treatment refers to reducing, decreasing, decreasing the risk of, or decreasing the side effects of a particular disease or condition. Reducing, decreasing, decreasing the risk of, or decreasing the side effects of are relative to a subject who did not receive treatment, e.g., a control, a baseline, or a known control level or measurement.
  • methods of treating rheumatoid arthritis in a subject are provided.
  • the rheumatoid arthritis is moderate to severe active rheumatoid arthritis.
  • the method comprises administering a pharmaceutical composition comprising administering an anti-FcRn antibody to the subject.
  • the anti-FcRn antibody is as provided for herein.
  • the subject being administered the anti-FcRn agent has demonstrated inadequate response to or is intolerant to at least one DMARD.
  • the subject being administered the anti-FcRn agent also receives at least one csDMARD treatment.
  • the administration of the pharmaceutical composition to the patient to treat rheumatoid arthritis results in the patient showing improvement in DAS28-CRP score, ACR20 response, ACR50 response, ACR70 response, ACR90 response, HAQ-DI score, CD Al score, SDAI score, pain VAS score, FACIT-fatigue score, joint pain severity score, PtGA of disease activity score, and/or SF-36 score.
  • the subject treated for rheumatoid arthritis, or moderate to severe active rheumatoid arthritis shows an improvement in one or more of the following assays, scores or criteria, which can be used to evaluate the improvement or condition of a subject with rheumatoid arthritis.
  • the subject shows improvement in one or more of the following: DAS28-CRP score, ACR20 response, ACR50 response, ACR70 response, ACR90 response, HAQ-DI score, CD Al score, SDAI score, pain VAS score, FACIT-fatigue score, joint pain severity score, PtGA of disease activity score, and SF-36 score.
  • the subject being treated for rheumatoid arthritis, or moderate to severe active rheumatoid arthritis has or shows a reduction in one or more immunoglobulin isotypes or total IgG.
  • the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 5-25%, 10-30%, 15-35%, 20-40%, 40-60%, or, about, or at least, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, or 90% from the baseline level.
  • the isotype of immunoglobulins reduced is IgGl, IgG2, IgG3, IgG4, IgA, IgM or IgE, or any combination thereof.
  • the administration of the pharmaceutical composition to the patient shows a reduction in one or more immunoglobulin isotypes or total IgG in the patient.
  • the isotype is IgGl, IgG2, IgG3, IgG4, IgA, IgM or IgE.
  • the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 5-25%, 10-30%, 15-35%, 20-40%, 40-60%, or, about, or at least, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, or 90% from the baseline level.
  • the subject being treated for rheumatoid arthritis, or moderate to severe active rheumatoid arthritis has or shows a reduction in autoantibodies.
  • the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5- 20%, 5-25%, 10-30%, 15-35%, 20-40%, 40-60%, or, about, or at least, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95% from the baseline level.
  • the reduction is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 1-20%, 5-20%, 5-25%, 10-30%, 15-35%, 20-40%, 40- 60%, or, about, or at least, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 95% from the baseline level.
  • the autoantibodies reduced are selected from the group consisting of: rheumatoid factors (RF), anti-perinuclear factor (APF), anti-carbamylated protein antibodies (anti-CarP), anti-acetylated protein antibodies (AAPAs) anti-citrullinated protein antibodies (ACPA), anti-keratin antibodies (AKA), anti-filaggrin antibodies (AFA), and combinations thereof.
  • RF rheumatoid factors
  • APF anti-perinuclear factor
  • anti-CarP anti-carbamylated protein antibodies
  • AAPAs anti-acetylated protein antibodies
  • ACPA anti-citrullinated protein antibodies
  • AKA anti-keratin antibodies
  • AFA anti-filaggrin antibodies
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the Disease Activity Index Score 28 using C-reactive protein (DAS28-CRP) score after being treated
  • the DAS28-CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and PtGA of Disease Activity (van Riel et al., Van Zuiden Communications B.V.; 2000:40).
  • the DAS28-CRP is a continuous parameter and is defined as follows:
  • DAS28-CRP 0.56 x SQRT(TEN28) + 0.28 x SQRT(SW28) + 0.36 x In (CRP+1) + 0.014 x GH + 0.96
  • the set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) 1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP) 1, PIP2, PIP3, PIP4, PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities.
  • TEN28 is 28-joint count for tenderness.
  • SQRT(TEN28) is square root of TEN28.
  • SW28 is 28-joint count for swelling.
  • SQRT(SW28) is square root of SW28.
  • Ln (CRP+1) is natural logarithm of (CRP value [mg/L] + 1).
  • GH is PtGA of Disease Activity on a VAS of 100 mm.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the Disease Activity Index Score 28 using Erthrocyte Sedimentation Rate (DAS28-ESR) score after being treated with the antibody.
  • DAS28-ESR Erthrocyte Sedimentation Rate
  • the DAS28-ESR is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), ESR, and GH (Prevoo 1995).
  • the DAS28-ESR is a continuous parameter and is defined as follows:
  • DAS28 (ESR) 0.56 x SQRT(TEN28) + 0.28 x SQRT(SW28) + 0.70 x In (ESR) + 0.014 x GH
  • the set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) 1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP) 1, PIP2, PIP3, PIP4, PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities.
  • TEN28 is 28 joint count for tenderness.
  • SQRT(TEN28) is square root of TEN28.
  • SW28 is 28 joint count for swelling.
  • SQRT(SW28) is square root of SW28.
  • Ln (ESR) is natural logarithm of ESR.
  • GH is PtGA of Disease Activity on a VAS of 100 mm.
  • DAS28 response is defined in Table A (van Riel 2000).
  • DAS28 low disease activity is defined as a DAS28 value of ⁇ 3.2 at a visit.
  • DAS28-CRP remission is defined as a DAS28 value of ⁇ 2.6 at a visit.
  • the improvement is greater than or equal to 0.6 points from baseline. In some embodiments, the improvement is greater than 0.6 but no greater than 1.2 points from baseline. In some embodiments, the improvement is greater than 1.2 points from baseline.
  • the administration of the pharmaceutical composition to the patient results in an improvement in the patient as measured by the DAS28-CRP score over time or 12 weeks after administration of the first dose of the pharmaceutical composition to the patient.
  • the baseline is the subject prior to be treated with the compositions or antibodies provided for herein.
  • the improvement i.e., a lower DAS28-CRP score
  • the improvement is greater than or equal to 0.6 points from baseline. In some embodiments, the improvement is greater than 0.6 but no greater than 1.2 points from baseline. In some embodiments, the improvement is greater than 1.2 points from baseline.
  • the administration of the pharmaceutical composition to the patient results in an improvement in the patient as measured by the DAS28- CRP score over time or 12 weeks after administration of the first dose of the pharmaceutical composition to the patient.
  • the baseline is the subject prior to be treated with the compositions or antibodies provided for herein.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the American College of Rheumatology Response (ACR) score after being treated with the antibody.
  • ACR responses are presented as the numerical measurement of improvement in multiple disease assessment criteria.
  • an ACR20 response (Felson et al., Arthritis Rheum. 1995;38(6):727-735) is defined as:
  • VAS Global Assessment of Disease Activity
  • VAS Assessment of pain
  • VAS Assessment of physical function as measured by HAQ-DI
  • Physician Global Assessment of Disease Activity
  • CRP CRP
  • VAS Global Assessment of Disease Activity
  • VAS Assessment of pain
  • VAS Assessment of physical function as measured by HAQ-DI
  • Physician Global Assessment of Disease Activity
  • CRP CRP
  • VAS Global Assessment of Disease Activity
  • VAS Assessment of pain
  • VAS Assessment of physical function as measured by HAQ-DI
  • Physician Global Assessment of Disease Activity
  • CRP CRP
  • an ACR90 response is defined as:
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) score after being treated with the antibody.
  • HAQ-DI Health Assessment Questionnaire - Disability Index
  • the functional status of the participant is assessed using the HAQ-DI (Fries 1980).
  • This 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area. A score decrease greater than or equal to 0.22 is considered the minimum threshold for a clinically important improvement (Kosinski 2000; Pope 2009; Wells 1993).
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the Clinical Disease Activity Index (CD Al) score after being treated with the antibody.
  • the Clinical Disease Activity Index (CD Al) score is a derived score combining tender joints (28 joints), swollen joints (28 joints), PtGA of Disease Activity, and PGA of Disease Activity (Aletaha 2006).
  • the CD Al score is defined as follows:
  • CD Al TEN28 + SW28 + GH + PGH
  • TEN28 is 28 joint count for tenderness.
  • SQRT(TEN28) is square root of TEN28.
  • SW28 is 28 joint count for swelling.
  • SQRT(SW28) is square root of SW28.
  • GH is PtGA of Disease Activity (VAS).
  • PGH is PGA of Disease Activity (VAS).
  • CD Al LDA is defined as a CD Al score of ⁇ 10 at a visit.
  • CD Al remission is defined as a CD Al score of ⁇ 2.8 at a visit.
  • the method comprises administering the anti-FcRn agent to the subject with rheumatoid arthritis and having a baseline ACPA level higher than the ACPA reference level, and the method provides a clinical benefit as measured by a decrease in DAS28- CRP by more than 0.7 from baseline within 12 weeks of initiation of treatment.
  • the subject achieved DAS28-CRP remission (i.e., a lower DAS28-CRP score) within 12 weeks of initiation of treatment.
  • the subject has at least a 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, or 120% higher chance of achieving DAS28- CRP remission within 12 weeks of treatment compared to subjects having an ACPA level lower than the ACPA reference level prior to treatment.
  • the subject achieved DAS28-CRP LDA within 12 weeks of initiation of treatment.
  • the subject achieved a decrease in Clinical Disease Activity Index (CD Al) by more than 10 from baseline within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in Health Assessment Questionnaire-Disability Index (HAQ-DI) by more than 0.4 from baseline within 12 weeks of initiation of the treatment.
  • CD Al Clinical Disease Activity Index
  • HAQ-DI Health Assessment Questionnaire-Disability Index
  • the subject achieved an ACR50 response within 12 weeks of initiation of the treatment. In some embodiments, the subject achieved an ACR70 response within 12 weeks of initiation of the treatment. In some embodiments, the subject achieved an ACR90 response within 12 weeks of initiation of the treatment.
  • initiation of treatment and “initiation of administering” are used interchangeably and refers to the start of the first dose of the composition comprising the anti-FcRn agent.
  • the subject achieved a decrease in DAS28-CRP by more than 0.9 from baseline within 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks of initiation of the csDMARD treatment. In some embodiments, the subject achieved a decrease in DAS28-CRP by more than 1.2 from baseline within 10 weeks, 11 weeks, or 12 weeks of initiation of the csDMARD treatment. In some embodiments, the subject achieved a decrease in Clinical Disease Activity Index (CD Al) by more than 10 from baseline within 12 weeks of initiation of the csDMARD treatment.
  • CD Al Clinical Disease Activity Index
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 0.8 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 1 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 1.2 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 1.4 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 1.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 1.8 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 2 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 2.2 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 2.4 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 2.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 2.8 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 3 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 3.2 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 3.4 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 3.6 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 3.8 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 4 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 4.2 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 4.4 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 4.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 4.8 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 5 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 5.2 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 5.4 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 5.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 5.8 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 6 from baseline within 12 weeks of initiation of treatment.. In some embodiments, the subject achieved DAS28-CRP LDA within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in CD Al by more than 11 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 13 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 15 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 17 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 19 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 21 from baseline within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in CD Al by more than 23 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 25 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 27 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 29 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 31 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 33 from baseline within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in CD Al by more than 35 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 37 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 39 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 41 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 43 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 45 from baseline within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in CD Al by more than 47 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 49 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 51 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 53 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 55 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 57 from baseline within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in CD Al by more than 59 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 61 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 63 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 65 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 67 from baseline within 12 weeks of initiation of the treatment. In some embodiment, the subject achieved a decrease in CD Al by more than 69 from baseline within 12 weeks of initiation of the treatment.
  • the subject achieved a decrease in CD Al by more than 70 from baseline within 12 weeks of initiation of the treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 0.5 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 0.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 0.7 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 0.8 from baseline within 12 weeks of initiation of treatment.
  • the subject achieved a decrease in HAQ-DI by more than 0.9 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.1 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.2 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.3 from baseline within 12 weeks of initiation of treatment.
  • the subject achieved a decrease in HAQ-DI by more than 1.4 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.5 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.7 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 1.8 from baseline within 12 weeks of initiation of treatment.
  • the subject achieved a decrease in HAQ-DI by more than 1.9 from baseline within 12 weeks of initiation of treatment. In some embodiments, the subject achieved a decrease in HAQ-DI by more than 2 from baseline within 12 weeks of initiation of treatment.
  • the patient achieves ACR20 after being treated with the antibody. In some embodiments, the patient achieves ACR50 after being treated with the anti-FcRn agent and the anti-TNF agent. In some embodiments, the patient achieves ACR70 after being treated with the anti-FcRn agent and the anti-TNF agent. In some embodiments, the patient achieves ACR90 after being treated with the anti-FcRn agent and the anti-TNF agent.
  • the administration of the pharmaceutical composition to the patient results in an improvement in the patient as measured by ACR score over time or 12 weeks after administration of the first dose of the anti-FcRn agent and the anti-TNF agent to the patient.
  • the subject achieves an ACR20 response within 12 weeks of initiation of treatment.
  • the subject achieves an ACR50 response within 12 weeks of initiation of treatment.
  • the subject achieves an ACR70 response within 12 weeks of initiation of treatment.
  • the subject achieves an ACR90 response within 12 weeks of initiation of treatment.
  • the improvement i.e., a score decrease
  • the administration of the pharmaceutical composition to the patient results in an improvement in HAQ-DI score over time or 12 weeks after administration of the first dose of the pharmaceutical composition to the patient.
  • the administration of the pharmaceutical composition to the patient results in an improvement of greater or equal to 0.22 on the HAQ-DI scale and indicates clinically important improvement.
  • the method provides a clinical benefit as measured by a decrease (i.e., an improvement) in HAQ-DI score by more than 0.4 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in HAQ-DI score by more than 0.5 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in HAQ-DI score by more than 0.6 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in HAQ-DI score by more than 0.7 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in HAQ-DI score by more than 0.8 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in HAQ-DI score by more than 0.9 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in HAQ-DI score by more than 1 from baseline within 12 weeks of initiation of treatment.
  • the baseline is the subject prior to be treated with the anti-FcRn agent and the anti- TNF agent.
  • the administration of the anti-FcRn agent and the anti-TNF agent to the patient results in a decreased in the CD Al baseline score over time or 12 weeks after initiation of the treatment. In some embodiments, the administration of the anti-FcRn agent and the anti-TNF agent to the patient results in a CD Al score that is less than 2.8 on the CD Al scale and indicates remission. In some embodiments, the administration of the anti-FcRn agent and the anti-TNF agent to the patient results a CD Al score that is less than or equal to 10 on the CD Al scale and indicates low disease activity. In some embodiments, the method provides a clinical benefit as measured by a decrease in CD Al score by more than 13 from baseline within 12 weeks of initiation of treatment.
  • the method provides a clinical benefit as measured by a decrease in CD Al score by more than 15 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) by more than 17, more than 19, more than 21, more than 23, more than 25, more than 27, more than 29, more than 31, more than 33, or more than 35 from baseline within 12 weeks of initiation of treatment.
  • CD Al Clinical Disease Activity Index
  • the method provides a clinical benefit as measured by a decrease in a CD Al score by more than 17 from baseline within 12 weeks of initiation of treatment. In some embodiments, the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) by more than 18, more than 19, more than 21, more than 23, more than 25, more than 27, more than 29, more than 31, more than 33, or more than 35, or more than 37, or more than 39 from baseline within 12 weeks of initiation of said administering.
  • the baseline is the subject prior to be treated with the compositions or antibodies provided for herein.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the Simplified Disease Activity Index (SDAI) score after being treated with the antibody.
  • SDAI Simplified Disease Activity Index
  • the Simplified Disease Activity Index (SDAI) for RA score is a derived score combining tender joints (28 joints), swollen joints (28 joints), PtGA of Disease Activity, PGA of Disease Activity, and CRP (Aletaha 2006).
  • the SDAI score is defined as follows:
  • SDAI TEN28 + SW28 + GH + PGH + CRP (mg/dL) where:
  • TEN28 is 28 joint count for tenderness.
  • SQRT(TEN28) is square root of TEN28.
  • SW28 is 28 joint count for swelling.
  • SQRT(SW28) is square root of SW28.
  • GH is Patient’s Global Assessment of Disease Activity (VAS).
  • PGH is Physician’s Global Assessment of Disease Activity (VAS).
  • SDAI LDA is defined as a SDAI score of ⁇ 5.5 at a visit. In some embodiments, the improvement is a SDAI score that is lesser than or equal to 5.5 points from baseline. In some embodiments, the improvement that is a SDAI score that is lesser than or equal to 5.5 points from baseline indicates SDAI LDA.
  • SDAI-based ACR/EULAR remission is defined as a SDAI value of ⁇ 3.3 at a visit (Felson 2011). In some embodiments, the improvement is a SDAI score that is lesser than or equal to 3.3 points from baseline. In some embodiments, the improvement that is a SDAI score that is lesser than or equal to 3.3 points from baseline indicates ACR/EULAR remission.
  • the administration of the pharmaceutical composition to the patient results in an improvement in SDAI baseline score over time or 12 weeks after administration of the first dose of the pharmaceutical composition to the patient. In some embodiments, the administration of the pharmaceutical composition to the patient results in an improvement that is a SDAI score that is lesser than or equal to 3.3 on the SDAI scale and indicates remission. In some embodiments, the administration of the pharmaceutical composition to the patient results in an improvement that is a SDAI score that is lesser than or equal to 5.5 on the SDAI scale and indicates low disease activity. In some embodiments, the administration of the pharmaceutical composition to the patient results in an improvement in PtGA of disease activity baseline score over time or 12 weeks after administration of the first dose of the pharmaceutical composition to the patient.
  • the administration of the pharmaceutical composition to the patient results in an improvement on the PtGA of disease activity scale.
  • the improvement on the PtGA of disease activity scale is a PtGA score that is lesser than or equal to 2.0 on the PtGA of disease activity scale and indicates low disease activity.
  • the baseline is the subject prior to be treated with the compositions or antibodies provided for herein.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the pain assessment score after being treated with the antibody. Participants are asked to assess their average pain during the past week on a VAS. The scale ranges from “no pain” to “the worst possible pain”. This assessment is completed prior to the joint examination. The validity of this assessment has been evaluated and reviewed extensively as it is a component of the ACR response score (Felson 1993; Hawley 1992).
  • the improvement is improvement in pain intensity from baseline.
  • the administration of the pharmaceutical composition to the patient results in an improvement in pain intensity from baseline.
  • the baseline is the subject prior to be treated with the compositions or antibodies provided for herein.
  • the improvement is at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, or 300% as compared to the baseline.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score after being treated with the antibody.
  • FACIT-Fatigue score is such that a higher score indicates less fatigue, with a range of possible scores of 0-52, with 0 being the worst possible score and 52 the best.
  • the FACIT-Fatigue can generally be completed in 5 minutes (Celia 2002; Yellen 1997).
  • the administration of the pharmaceutical composition to the patient results in an improvement from baseline on FACIT-Fatigue scale.
  • the score increases at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, or 300% as compared to the baseline.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by joint pain score after being treated with the antibody.
  • Participants’ joint pain is assessed using a single item that asks the participant to report the worst severity of their joint pain over the past 7 days on a 0 to 10 numeric rating scale (NRS).
  • NRS numeric rating scale
  • the administration of the pharmaceutical composition to the patient results in an improvement from baseline on NRS scale. Responses range from 'No joint pain' (0) to 'Severe joint pain' (10).
  • the improvement is at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, or 300% as compared to the baseline.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by joint pain score after being treated with the antibody.
  • Participants' joint pain is assessed using a single item that asks the participant to report the worst severity of their joint pain over the past 7 days on a 0 to 10 numeric rating scale (NRS).
  • NRS numeric rating scale
  • the administration of the pharmaceutical composition to the patient results in an improvement from baseline on NRS scale. Responses range from 'No joint pain' (0) to 'Severe joint pain' (10).
  • the improvement is at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, or 300% as compared to the baseline.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by joint assessments score after being treated with the antibody.
  • Each of 68 joints is evaluated for tenderness, and each of 66 joints is evaluated for swelling (hips are excluded for swelling). All joints are examined at visits. It is recommended that the joint assessor should not be changed during the study. Joints should only be designated as “non-evaluable” by the joint assessor on the Joint Assessment Worksheet if it is physically impossible to assess the joint (i.e., joint inaccessible due to a cast, joint was replaced, joint not present due to an amputation, joint deformed so as to make it impossible to assess).
  • the joint assessor should assess each joint for tenderness and swelling (hips are excluded for swelling) and complete the worksheet with their assessments. This should be completed regardless of any visual indications of prior surgeries (e.g., scars) or knowledge they may have of a participant’s prior joint procedures/inj ections (e.g., if the participant was the joint assessor’s patient prior to study participation).
  • the improvement is at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, or 300% as compared to the baseline.
  • the subject being treated for rheumatoid arthritis, or moderate to severe rheumatoid arthritis shows an improvement as measured by the 36-item Short Form Health Survey Questionnaire (SF-36) score after being treated with the antibody.
  • SF-36 version 2 Standard health survey is a self-administered, 36-item questionnaire measuring health related quality of life, with a recall period of the past 4 weeks. It includes 8 domains that measure physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems and mental health.
  • the 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component scale (PCS) and a mental component score (MCS).
  • PCS physical component scale
  • MCS mental component score
  • the administration of the pharmaceutical composition to the patient results in an improvement from baseline on SF- 36 scale.
  • the administration of the pharmaceutical composition to the patient results in an improvement from baseline on PCS scale.
  • the administration of the pharmaceutical composition to the patient results in an improvement from baseline on MCS scale.
  • the improvement is an improvement on the physical health scale.
  • the improvement is an improvement on the mental health scale.
  • the improvement is an improvement on the physical and mental health scale. In some embodiments, the improvement is at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 250%, or 300% as compared to the baseline.
  • the term “change” in reference to a baseline refers to a subject having an improvement as compared to that subject’s conditions, scores, symptoms, and the like prior to being treated with the anti-FcRn antibodies as provided for herein.
  • Baseline refers to a subject prior to being treated with a therapeutic, such as the anti- FcRn agent, including those described herein.
  • the improvement in symptoms or conditions are referred to as occurring 12 weeks after initiation of treatment.
  • the improvements or changes described herein will occur within 2, 4, 6, 8, 10, 12, 14, 16, or 18 weeks. In some embodiments, the changes or improvements will last at least 2, 4, 6, 8, 10, 12, 14, 16, 18 weeks, or longer.
  • the subject being treated for rheumatoid arthritis, or moderate to severe active rheumatoid arthritis with an anti-FcRn agent has been previously treated with a different therapeutic to treat the rheumatoid arthritis, or moderate to severe active rheumatoid arthritis.
  • the subject has previously been treated with glucocorticoids, immunosuppressives, pharmacological gland stimulant, topical ophthalmologic medication (other than artificial tears), hydroxychloroquine (or other antimalarial); NSAIDs, Methotrexate, Leflunomide, rituximab, anti-BAFF monoclonal antibody, or other B cell depleting therapeutic, anti -tumor necrosis factor (TNF) therapeutic, or other biologic medication (e.g., tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra, brodalumab, secukinumab, ixekizumab, or agents whose mechanism of action targets interleukin (IL) 1, IL-2, IL-6, IL- 17, cytotoxic T- lymphocyte-associated protein (CTLA) 4, or interferon pathway drugs), cyclosporine A, tacrolimus, or pime
  • the subject has previously been treated with a first anti-FcRn agent and is then switched to a different anti-FcRn agent.
  • the subject has been previously treated with a therapeutic to treat the rheumatoid arthritis that is not an anti-FcRn agent described herein (e.g., the anti-FcRn antibody nipocalimab).
  • the subject being treated for rheumatoid arthritis is a subject in need thereof.
  • the subject being treated for rheumatoid arthritis with an anti- FcRn agent does not experience significantly increased levels of total cholesterol, high-density lipoprotein (HDL), calculated low-density lipoprotein (LDL), and triglycerides after being treated with the agent.
  • the anti-FcRn agent is an anti-FcRn antibody as provided herein.
  • the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of total cholesterol after being treated with the antibody.
  • the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of high- density lipoprotein (HDL) after being treated with the antibody. In some embodiments, the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of calculated low-density lipoprotein (LDL) after being treated with the antibody. In some embodiments, the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of triglycerides after being treated with the antibody.
  • HDL high- density lipoprotein
  • LDL calculated low-density lipoprotein
  • the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of total cholesterol after being treated with the anti-FcRn antibody. In some embodiments, the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of high-density lipoprotein (HDL) after being treated with the anti- FcRn antibody. In some embodiments, the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of calculated low-density lipoprotein (LDL) after being treated with the anti-FcRn antibody. In some embodiments, the subject being treated for rheumatoid arthritis with an anti-FcRn antibody does not experience significantly increased levels of triglycerides after being treated with the anti-FcRn antibody.
  • HDL high-density lipoprotein
  • LDL calculated low-density lipoprotein
  • the administration of the pharmaceutical composition to the patient does not significantly increase levels of total cholesterol, high-density lipoprotein (HDL), calculated low-density lipoprotein (LDL), and triglycerides after administration of the pharmaceutical composition comprising the antibody.
  • the antibody is an anti-FcRn antibody.
  • the anti-FcRn antibody is as provided herein.
  • the administration of the pharmaceutical composition to the patient does not significantly increase levels of total cholesterol after administration of the pharmaceutical composition comprising the antibody.
  • the administration of the pharmaceutical composition to the patient does not significantly increase levels of high-density lipoprotein (HDL) after administration of the pharmaceutical composition comprising the antibody.
  • the administration of the pharmaceutical composition to the patient does not significantly increase levels of calculated low-density lipoprotein (LDL) after administration of the pharmaceutical composition comprising the antibody. In some embodiments, the administration of the pharmaceutical composition to the patient does not significantly increase levels of triglycerides after administration of the pharmaceutical composition comprising the antibody. In some embodiments, the administration of the pharmaceutical composition to the patient does not significantly increase levels of total cholesterol after administration of the pharmaceutical composition comprising the anti-FcRn antibody. In some embodiments, the administration of the pharmaceutical composition to the patient does not significantly increase levels of high-density lipoprotein (HDL) after administration of the pharmaceutical composition comprising the anti-FcRn antibody.
  • HDL high-density lipoprotein
  • the administration of the pharmaceutical composition to the patient does not significantly increase levels of calculated low-density lipoprotein (LDL) after administration of the pharmaceutical composition comprising the anti-FcRn antibody. In some embodiments, the administration of the pharmaceutical composition to the patient does not significantly increase levels of triglycerides after administration of the pharmaceutical composition comprising the anti-FcRn antibody.
  • LDL low-density lipoprotein
  • the phrase “does not significantly increase” when used in reference to levels (measurements) of total cholesterol, high-density lipoprotein (HDL), calculated low- density lipoprotein (LDL), or triglycerides” means that any increase is at most 30% as compared to the level(s) prior (baseline) to the administration of the antibody or compositions provided for herein. In some embodiments, the increase is at most 25%, 20%, 15%, 10%, or 5%.
  • the increase is at most about 1% to about 30%, about 5% to about 25%, about 1% to about 20%, about 1% to about 15%, about 1% to about 10%, about 5% to about 15%, about 5% to about 20%, about 10% to about 20%, about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, or about 30%.
  • the term “about” means that the numerical value is approximate and small variations would not significantly affect the practice of the disclosed embodiments. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by ⁇ 10% and remain within the scope of the disclosed embodiments.
  • compositions are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
  • Any composition or method that recites the term “comprising” should also be understood to also describe such compositions as consisting, consisting of, or consisting essentially of the recited components or elements.
  • the term “individual,” “subject,” or “patient,” can be used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans.
  • the term “mammal” means a rodent (i.e., a mouse, a rat, or a guinea pig), a monkey, a cat, a dog, a cow, a horse, a pig, or a human. In some embodiments, the mammal is a human.
  • the phrase “in need thereof’ means that the subject has been identified as having a need for the method or treatment. In some embodiments, the identification can be by any means of diagnosis. In any of the methods and treatments described herein, the subject can be in need thereof. In some embodiments, the subject is in an environment or will be traveling to an environment in which a particular disease, disorder, or condition is prevalent.
  • a method of treating or reducing severity of rheumatoid arthritis in a subject in need thereof comprising administering an anti-neonatal Fc receptor (FcRn) agent to the subject, wherein, prior to the subject receiving an initial administration of the anti-FcRn agent, an anti-citrullinated protein antibody (ACPA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level.
  • FcRn anti-neonatal Fc receptor
  • ACPA anti-citrullinated protein antibody
  • a method of treating or reducing severity of rheumatoid arthritis in a subject in need thereof comprising (a) determining an ACPA level in a blood sample from the subject;
  • step (b) administering an anti-neonatal Fc receptor (FcRn) agent to the subject if the ACPA level determined in step (a) is higher than an ACPA reference level.
  • FcRn anti-neonatal Fc receptor
  • ACPA reference level is about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or 1000 U/ml.
  • DMARD disease-modifying antirheumatic drug
  • TNF anti-tumor necrosis factor
  • the anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • the anti-TNF agent is adalimumab, etanercept, golimumab, or infliximab.
  • JAK inhibitor is tofacitinib, baricitinib, or upadacitinib.
  • DMARD is an anti-interleukin-6 (IL-6) agent.
  • IL-6 anti-interleukin-6
  • T-cell costimulation inhibitor is abatacept.
  • DMARD is an anti-interleukin- 1 (IL-1) agent.
  • IL-1 anti-interleukin- 1
  • anti-FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, orilanolimab, SYNT002, ABY- 039, or DX-2507.
  • anti-FcRn agent is an anti- FcRn antibody comprising:
  • a light chain which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and (b) a heavy chain, which comprises a CDRH1 comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.
  • TNF anti-tumor necrosis factor
  • anti-TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • a light chain which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 42, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 43, a CDR L3 comprising an amino acid sequence of SEQ ID NO: 44; and
  • the anti-TNF agent is an anti-TNF antibody comprising (a) a light chain comprising an amino acid sequence of SEQ ID NO: 29; and (b) a heavy chain comprising an amino acid sequence of SEQ ID NO: 30. 61. The method of any one of claims 49-55 and 60, wherein the anti-TNF agent is certolizumab pegol.
  • An anti-FcRn agent for use in a method of treating or reducing severity of rheumatoid arthritis in a subject in need thereof, the method comprising administering the anti-FcRn agent to the subject, wherein, prior to the subject receiving an initial administration of the anti-FcRn agent, an anti-cyclic citrullinated peptide autoantibody (ACPA) level in a blood sample from the subject is or has been found to be higher than an ACPA reference level.
  • ACPA anti-cyclic citrullinated peptide autoantibody
  • step (b) administering an anti-neonatal Fc receptor (FcRn) agent to the subject if the ACPA level determined in step (a) is higher than an ACPA reference level.
  • FcRn anti-neonatal Fc receptor
  • any one of claims 66-69 wherein the ACPA reference level is about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, or 1000 U/ml.
  • TNF anti-tumor necrosis factor
  • anti-FcRn agent for use according to claim 78, wherein the anti-TNF agent is adalimumab, etanercept, golimumab, or infliximab.
  • IL-6 antiinterleukin-6
  • IL-1 antiinterleukin-1
  • anti-FcRn agent for use according to claim 89, wherein the anti-IL-1 agent is anakinra.
  • anti-FcRn agent for use according to any one of claims 66-94, wherein the method provides a clinical benefit as measured by a decrease in Health Assessment Questionnaire- Disability Index (HAQ-DI) in the subject by more than 0.4 from baseline within 12 weeks of initiation of said administering.
  • HAQ-DI Health Assessment Questionnaire- Disability Index
  • anti-FcRn agent for use according to any one of claims 66-95, further comprising administering at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD).
  • csDMARD synthetic disease modifying anti-rheumatic drug
  • the anti-FcRn agent for use according to claim 96 wherein the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 0.9 from baseline within 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks of initiation of said administering the at least one csDMARD.
  • the anti-FcRn agent for use according to claim 96 wherein the method provides a clinical benefit as measured by a decrease in DAS28-CRP in the subject by more than 1.2 from baseline within 10 weeks, 11 weeks, or 12 weeks of initiation of said administering the at least one csDMARD.
  • anti-FcRn agent for use according to any one of claims 96-98, wherein the method provides a clinical benefit as measured by a decrease in Clinical Disease Activity Index (CD Al) in the subject by more than 10 from baseline within 12 weeks of initiation of said administering the at least one csDMARD.
  • CD Al Clinical Disease Activity Index
  • anti-FcRn agent for use according to any one of claims 96-99, wherein the csDMARD is methotrexate, hydroxychloroquine, leflunomide, or sulfasalazine.
  • anti-FcRn agent for use according to any one of claims 66-100, wherein the subject achieves an ACR50 response within 12 weeks of initiation of said administering.
  • anti-FcRn agent for use according to any one of claims 66-103, wherein the anti- FcRn agent is administered every week or every two weeks.
  • anti-FcRn agent for use according to any one of claims 66-104, wherein the anti- FcRn agent is administered intravenously or subcutaneously.
  • anti-FcRn agent for use according to any one of claims 66-107, wherein the anti- FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, onlanolimab, SYNT002, ABY- 039, or DX-2507.
  • anti-FcRn agent for use according to any one of claims 66-108, wherein the anti- FcRn agent is an anti-FcRn antibody comprising:
  • a light chain which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and
  • a heavy chain which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.
  • the anti-FcRn agent for use according to claim 109 wherein (a) the light chain of the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 9; and (b) the heavy chain of the anti-FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 10.
  • the anti-FcRn agent for use according to claim 109 or claim 110 wherein (a) the light chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 1; and (b) the heavy chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 2.
  • anti-FcRn agent for use according to any one of claims 66-111 , wherein the anti- FcRn agent is nipocalimab.
  • the method further comprises administering an anti -tumor necrosis factor (TNF) agent to the subject.
  • TNF anti -tumor necrosis factor
  • the anti-FcRn agent for use according to claim 114 wherein the subject demonstrated inadequate response to or is intolerant to a previous anti-TNF agent, which is different from the TNF agent administered to the subject.
  • anti-FcRn agent for use according to claim 114 or claim 115, wherein the anti-FcRn agent is administered separately, simultaneously, or sequentially with the anti-TNF agent.
  • anti-FcRn agent for use according to any one of claims 114-116, wherein the anti- FcRn agent is administered sequentially with the anti-TNF agent.
  • anti-FcRn agent for use according to any one of claims 114-116, wherein the anti- FcRn agent is administered simultaneously with the anti-TNF agent.
  • anti-FcRn agent for use according to any one of claims 114-118, wherein the anti- TNF agent is administered intravenously or subcutaneously.
  • anti-FcRn agent for use according to any one of claims 114-119, wherein the anti- TNF agent is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, every 6 weeks, or every 8 weeks.
  • anti-FcRn agent for use according to any one of claims 114-120, wherein the anti- TNF agent is adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab.
  • anti-FcRn agent for use according to any one of claims 114-121, wherein the anti- TNF agent is an anti-TNF antibody comprises:
  • a light chain which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 42, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 43, a CDR L3 comprising an amino acid sequence of SEQ ID NO: 44; and
  • a heavy chain which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 45, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 46, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 47.
  • the anti-FcRn agent for use according to claim 122 wherein (a) the light chain of the anti-TNF antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48; and (b) the heavy chain of the anti-TNF antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 49.
  • the anti-FcRn agent for use according to claim 122 or claim 123 wherein (a) the light chain of the anti-TNF antibody comprises an amin acid sequence of SEQ ID NO: 40; and (b) the heavy chain of the anti-TNF antibody comprises an amino acid sequence of SEQ ID NO: 41.
  • anti-FcRn agent for use according to any one of claims 114-124, wherein the anti- TNF agent is golimumab.
  • anti-FcRn agent for use according to any one of claims 114-125, wherein the anti- TNF agent is an anti-TNF antibody comprising (a) a light chain comprising an amino acid sequence of SEQ ID NO: 29; and (b) a heavy chain comprising an amino acid sequence of SEQ ID NO: 30.
  • CD Al Clinical Disease Activity Index
  • HAQ-DI Health Assessment Questionnaire- Disability Index
  • a kit comprising an anti-neonatal Fc receptor (FcRn) agent and an anti-tumor necrosis factor (TNF) agent to the subject.
  • FcRn anti-neonatal Fc receptor
  • TNF anti-tumor necrosis factor
  • kit of any one of claims 135-140 further comprising instructions for a method of treating or reducing severity of rheumatoid arthritis in a subject.
  • the kit of claim 141 wherein the method is a method as defined in any one of claims 49- 65.
  • Example 1 Clinical Trial to Evaluate Efficacy and Safety of Anti-FcRn Antibodies for Treatment of Rheumatoid Arthritis
  • FIG. 1 depicts a schematic overview of the study.
  • the total duration of the study was up to 24 weeks and involved 3 study periods: a ⁇ 6- week screening period (rescreening is permitted once per subject), a 12-week double-blind treatment period, and a 6-week safety follow-up period (8 weeks after the last study intervention administration).
  • MTX Baseline Methotrexate
  • Baseline swollen and tender joint counts (28) are part of the components used to drive DAS28.
  • concomitant therapies for RA i.e., conventional synthetic disease modifying antirheumatic drugs (csDMARDs), oral corticosteroids, non-steroidal antiinflammatory drugs (NSAIDs), and other analgesics
  • csDMARDs conventional synthetic disease modifying antirheumatic drugs
  • NSAIDs non-steroidal antiinflammatory drugs
  • This example provides the analysis results for primary and key efficacy endpoints, safety, and biomarker data through Week 12.
  • the primary endpoint was the mean change from baseline in Disease Activity Index Score 28 using C-reactive protein (CRP) [DAS28-CRP] at Week 12.
  • CRP C-reactive protein
  • the DAS28-CRP score is calculated based on the tender joints (28), swollen joints (28), patient’s global assessment of disease activity, and CRP.
  • Change from baseline in DAS28-CRP measures the change in disease activity, where a negative change indicates an improvement, and a positive change indicates a worsening.
  • HAQ- DI Health Assessment Questionnaire Disability Index
  • the difference of 1 was derived by a meta-analysis of effective treatments in RA.
  • LS Least Square
  • CI 95% confidence intervals
  • Lor continuous endpoints e.g., change from baseline in DAS28-CRP and change from baseline in HAQ-DI
  • Lor binary endpoints e.g., ACR20, ACR50, ACR70, ACR90, DAS28-CRP remission, and DAS28 (LDA) response
  • treatment groups were compared using a 2-sided Cochran-Mantel- Haenszel [CMH] chi-square test. If small number, the Lisher’s exact test was used instead of the CMH test.
  • Multiplicity adjustment There were no adjustments for multiple comparisons. All tests were performed at a 2-sided significance level of 0.05. All p-values presented are nominal.
  • Nipocalimab 15 mg/kg IV q2w demonstrated numerically higher improvement in the primary endpoint (change from baseline at Week 12 in DAS28-CRP) compared to placebo. Similar results were obtained in participants who were receiving csDMARDs at baseline: nipocalimab 15 mg/kg IV q2w demonstrated numerically higher improvement from baseline in DAS28-CRP at Week 12 compared to placebo. Additionally, nipocalimab treated participants had numerically higher rates of ACR responses and DAS28-CRP remission at Week 12 compared to those treated with placebo. Change from baseline in all ACR components, except CRP, showed numerically bigger improvement for nipocalimab compared to placebo treated participants generally starting from Week 6 and through Week 12. Further, nipocalimab treated participants had numerically bigger improvement from baseline in Clinical Disease Activity Index (CD Al) over time compared to placebo treated.
  • CD Al Clinical Disease Activity Index
  • Secondary Endpoint Subjects achieving DAS28-CRP Remission and LDA at Week 12. A numerically higher proportion of participants achieved DAS28-CRP remission at Week 12 based on the main composite estimand [7 (21.2%)] in the nipocalimab group than the placebo group [2 (10.0%)] (Table 7). There were no participants who achieved DAS28 (LDA) response at Week 12. Compared to the placebo group, a numerically higher proportion of participants in the nipocalimab group achieved DAS28-CRP remission over time. Secondary Endpoint: Change from Baseline in HAQ-DI Score at Week 12.
  • Nipocalimab treated participants achieved a numerically higher mean improvement in HAQ-DI [-0.42 (-0.66; - 0.19)] compared to placebo [-0.21 (-0.45; 0.04)] at Week 12.
  • the LSMean difference between the groups was [-0.22 (-0.49; 0.05)] (Table 8).
  • nipocalimab treated participants experienced at least 1 AE in the following system organ class (preferred term): infections (covid- 19, nasopharyngitis); musculoskeletal (RA), general disorders (chills, fatigue); nervous system (headache); skin and subcutaneous (rash).
  • Baseline biomarker levels were generally comparable between the nipocalimab and placebo groups. Relative to the baseline, no changes in complement activation markers or serum inflammatory markers were observed in either group.
  • Serum total IgG levels were reduced by nipocalimab from Weeks 4 through 12 and returned to baseline level at Week 18.
  • Week 12 there was a 58% reduction (geometric mean) in the total IgG levels observed in the nipocalimab group, compared to a 2.4% increase in the placebo group (FIG. 2A).
  • the serum total IgG returned to baseline level at Week 18. Decreases from baseline in all IgG subclasses were consistent with those observed for total IgG levels.
  • significant reductions of CIC (circulating immune complex) levels were observed in the nipocalimab group versus the placebo group and correlated with total IgG reduction (FIG. 2B).
  • anti-cyclic citrullinated protein autoantibodies also known as antibody to citrullinated protein antigens (ACPA)
  • ACPA antibody to citrullinated protein antigens
  • ACPA level was determined using a second generation anti-CCP test (CCP2) kit, IMMUNOSCAN CCPlus obtained from SVAR, which is based on an ELISA method. Briefly, the test utilized microtiter plate wells coated with citrullinated synthetic peptides (antigen). Diluted patient serum was applied to the wells and incubated. If specific antibodies were present, they would bind to the antigen in the wells. Unbound material was washed away and any bound antibody was detected by adding horse radish peroxidase (HRP) labelled anti-human IgG, followed by a second washing step and an incubation with substrate. The presence of reacting antibodies would result in the development of color, which was proportional to the quantity of bound antibody, and this was determined photometrically.
  • CCP2 second generation anti-CCP test
  • DAS28-CRP % remission rate and ACR50 % response rate for patients with baseline ACPA levels at or higher than various ACPA reference levels (ACPA- high patients) within the nipocalimab group and placebo group were compared and tabulated in Table 15.
  • the ACPA reference level was set at 200 U/ml
  • 67.9% of the total patients were ACPA-high patients (i.e., having an ACPA level at or above the ACPA reference level of 200 U/ml)
  • the DAS28-CRP remission rate for ACPA-high patients in nipocalimab group and placebo group was 25% (6/24) and 16.7% (2/12), respectively
  • the ACR50 response rate for ACPA-high patients in nipocalimab group and placebo group was 16.7% (4/24) and 0% (0/12), respectively.
  • the ACPA reference level was set at 600 U/ml
  • 37.7% of the total patients were ACPA-high patients (i.e., having an ACPA level at or above the ACPA reference level of 600 U/ml)
  • the DAS28-CRP remission rate for ACPA-high patients in nipocalimab group and placebo group was 40% (4/10) and 20% (2/10), respectively
  • the ACR50 response rate for ACPA-high patients in nipocalimab group and placebo group was 30% (3/10) and 0% (0/10), respectively.
  • the bottom row of Table 15 listed the DAS28-CRP remission rate and ACR50 response rate of total patients within nipocalimab group and placebo group.
  • the % rate of patients in each ACPA-high subgroups achieving DAS28-CRP remission is higher compared to that of all patients in nipocalimab group
  • the % rate of patients in each ACPA-high subgroups achieving ACR50 response is higher compared to that of all patients in nipocalimab group.
  • Nipocalimab 15mg/kg IV q2w was in general well tolerated, however, 2 SAEs reported in the study, and both occurred in the nipocalimab group. A higher proportion of nipocalimab treated participants experienced infusion reactions and infections compared to those treated with placebo.
  • Acetylsalicylic Acid 1 (5.0%) 2 (6.1%) 3 (5.7%)
  • Ketoprofen 3 (15.0%) 0 3 (5.7%)
  • the DAS28-CRP score is calculated based on the tender joints (28), swollen joints (28), patient’s global assessment of disease activity, and CRP. Change from baseline in DAS28-CRP measures the change in disease activity, where a negative change indicates an improvement, and a positive change indicates a worsening.
  • IQ interquartile
  • ICE Intercurrent Event
  • ANCOVA Analysis of Covariance
  • CI Confidence Interval
  • CRP C-reactive protein
  • Table 4 Primary Endpoint Analysis (Supplementary Analysis, Supplementary Estimand): Summary of Change from Baseline in DAS28-CRP Score at Week 12 Using an ANCOVA Model; Full _ Analysis Set _
  • the DAS28-CRP score is calculated based on the tender joints (28), swollen joints (28), patient’s global assessment of disease activity, and CRP. Change from baseline in DAS28-CRP measures the change in disease activity, where a negative change indicates an improvement, and a positive change indicates a worsening.
  • IQ interquartile
  • ICE Intercurrent Event
  • ANCOVA Analysis of Covariance
  • CI Confidence Interval
  • Table 5 Tertiary Endpoint Analysis (Main Analysis, Main Estimand): Summary of Change from Baseline _ in DAS28(CRP) Score by Visit Through Week 12 Using an ANCOVA Model; Full Analysis Set
  • the DAS28-CRP score is calculated based on the tender joints (28), swollen joints (28), patient’s global assessment of disease activity, and CRP. Change from baseline in DAS28-CRP measures the change in disease activity, where a negative change indicates an improvement, and a positive change indicates a worsening.
  • IQ interquartile
  • ICE Intercurrent Event
  • ANCOVA Analysis of Covariance
  • CI Confidence Interval
  • CRP C-reactive protein
  • Table 6 Number of Subjects Who Achieved ACR20, ACR50, ACR70, or ACR90 Response at Week 12
  • the DAS28-CRP remission is defined as DAS28-CRP value of ⁇ 2.6 at Week 12
  • Table 8 Secondary Endpoint Analysis (Main Analysis, Main Estimand): Summary of Change from _ Baseline in HAQ-DI Score at Week 12 Using an ANCOVA Model; Full Analysis Set _
  • HAQ-DI score ranges from 0-3, with lower scores indicative of better function in subjects
  • IQ interquartile
  • ICE Intercurrent Event
  • ANCOVA Analysis of Covariance
  • CI Confidence Interval
  • HAQ-DI- Health Assessment Questionnaire HAQ-DI- Health Assessment Questionnaire
  • DI Disability Index
  • the Clinical Disease Activity Index (CDAI) score is a derived score combining 4 disease assessments: tender joint counts (28 joints), swollen joint counts (28 joints), Patient’s Global Assessment of Disease Activity (PtGA), and Physician’s Global Assessment of Disease Activity (PGA)
  • IQ interquartile
  • ICE-lntercurrent Event ANCOVA- Analysis of Covariance
  • CI Confidence Interval
  • Table 10 Tertiary Endpoint Analysis (Main Analysis, Main Estimand): Summary of Change from Baseline in DAS28-CRP Score by Visit Through Week 12 by Baseline csDMARDs Usage Using an ANCOVA Model; Full Analysis Set
  • the DAS28-CRP score is calculated based on the tender joints (28), swollen joints (28), patient’s global assessment of disease activity, and CRP. Change from baseline in DAS28-CRP measures the change in disease activity, where a negative change indicates an improvement, and a positive change indicates a worsening.
  • IQ interquartile
  • ICE Intercurrent Event
  • ANCOVA Analysis of Covariance
  • CI Confidence Interval
  • CRP C-reactive protein
  • Table 11 Number of Subjects Who Achieved an ACR20 Response by Visit Through Week 12 by Baseline csDMARDs Usage, Based on Main Estimand; Full Analysis Set
  • Table 11 Number of Subjects Who Achieved an ACR20 Response by Visit Through Week 12 by Baseline _ csDMARDs Usage, Based on Main Estimand; Full Analysis Set _
  • ACR20 response is defined as > 20% improvement from baseline in both tender joint count (68 joints) and swollen joint count (66 joints), and > 20% improvement from baseline in at least 3 of the 5 assessments: patient’s assessment of pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, HAQ -DI, and CRP
  • ICE Intercurrent Event
  • CRP C-reactive protein
  • HAQ-DI Health Assessment Questionnaire (HAQ) Disability Index (DI)
  • Table 12 Number of Subjects Who Achieved an ACR50 Response by Visit Through Week 12 by Baseline csDMARDs Usage, Based on Main Estimand; Full Analysis Set
  • ACR50 response is defined as > 50% improvement from baseline in both tender joint count (68 joints) and swollen joint count (66 joints), and > 50% improvement from baseline in at least 3 of the 5 assessments: patient’s assessment of pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, HAQ -DI, and CRP
  • ICE Intercurrent Event
  • CRP C-reactive protein
  • HAQ-DI Health Assessment Questionnaire (HAQ) Disability Index (DI)
  • Table 13 Tertiary Endpoint Analysis (Main Analysis, Main Estimand) Change from Baseline in CDAI by Visit Through Week 12 by Baseline csDMARDs Usage Using an ANCOVA Model; Full Analysis _ Set _ _ Nipocalimab _ Placebo 15 mg/kg IV q2w
  • Table 13 Tertiary Endpoint Analysis (Main Analysis, Main Estimand) Change from Baseline in CDAI by Visit Through Week 12 by Baseline csDMARDs Usage Using an ANCOVA Model; Full Analysis Set

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Abstract

L'invention concerne une composition et des méthodes de traitement de la polyarthrite rhumatoïde faisant appel à des compositions comprenant des agents anti-FcRn et éventuellement en combinaison avec des agents anti-TNF.
PCT/IB2024/060934 2023-11-06 2024-11-05 Compositions et méthodes de traitement de la polyarthrite rhumatoïde Pending WO2025099576A1 (fr)

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Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5395760A (en) 1989-09-05 1995-03-07 Immunex Corporation DNA encoding tumor necrosis factor-α and -β receptors
US5605690A (en) 1989-09-05 1997-02-25 Immunex Corporation Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor
WO2004041862A2 (fr) 2002-11-08 2004-05-21 Ablynx N.V. Anticorps a domaine unique diriges contre le facteur de necrose tumorale alpha et leurs utilisations
US7012135B2 (en) 2000-06-06 2006-03-14 Celltech Chiroscience Limited Biological products
US7070775B2 (en) 1991-03-18 2006-07-04 New York University Recombinant A2-specific TNFα specific antibodies
US7250165B2 (en) 2000-08-07 2007-07-31 Centocor, Inc. Anti-TNF antibodies, compositions, methods and uses
US20140248287A1 (en) * 2008-04-25 2014-09-04 Syntonix Pharmaceuticals, Inc. Fc receptor binding proteins
WO2016065323A2 (fr) 2014-10-23 2016-04-28 Singh Biotechnology, Llc Anticorps à domaine unique dirigés contre des antigènes intracellulaires
US9862768B2 (en) 2011-06-02 2018-01-09 Dyax Corp. Methods of producing antibodies to neonatal Fc receptor (FcRn)
US10233243B2 (en) 2012-05-14 2019-03-19 Ucb Biopharma Sprl Anti-FcRn antibodies
US10316073B2 (en) 2013-12-24 2019-06-11 Argenx Bvba FCRN antagonists and methods of use
US10323066B2 (en) 2014-09-17 2019-06-18 Affibody Ab Neonatal Fc receptor binding dimer and methods of use
US10544226B2 (en) 2014-04-30 2020-01-28 Hanall Biopharma Co., Ltd. Antibody binding to FcRn for treating autoimmune diseases
US10626175B2 (en) 2015-05-12 2020-04-21 Syntimmune, Inc. Humanized affinity matured anti-FcRn antibodies
US10676526B2 (en) 2015-01-30 2020-06-09 Momenta Pharmaceuticals, Inc. FcRn antibodies and methods of use thereof
US10822417B2 (en) 2016-04-25 2020-11-03 Syntimmune, Inc. Humanized affinity matured anti-FcRn antibodies

Patent Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5395760A (en) 1989-09-05 1995-03-07 Immunex Corporation DNA encoding tumor necrosis factor-α and -β receptors
US5605690A (en) 1989-09-05 1997-02-25 Immunex Corporation Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor
US7070775B2 (en) 1991-03-18 2006-07-04 New York University Recombinant A2-specific TNFα specific antibodies
US7012135B2 (en) 2000-06-06 2006-03-14 Celltech Chiroscience Limited Biological products
US7250165B2 (en) 2000-08-07 2007-07-31 Centocor, Inc. Anti-TNF antibodies, compositions, methods and uses
WO2004041862A2 (fr) 2002-11-08 2004-05-21 Ablynx N.V. Anticorps a domaine unique diriges contre le facteur de necrose tumorale alpha et leurs utilisations
US20140248287A1 (en) * 2008-04-25 2014-09-04 Syntonix Pharmaceuticals, Inc. Fc receptor binding proteins
US9862768B2 (en) 2011-06-02 2018-01-09 Dyax Corp. Methods of producing antibodies to neonatal Fc receptor (FcRn)
US10233243B2 (en) 2012-05-14 2019-03-19 Ucb Biopharma Sprl Anti-FcRn antibodies
US10316073B2 (en) 2013-12-24 2019-06-11 Argenx Bvba FCRN antagonists and methods of use
US10544226B2 (en) 2014-04-30 2020-01-28 Hanall Biopharma Co., Ltd. Antibody binding to FcRn for treating autoimmune diseases
US10323066B2 (en) 2014-09-17 2019-06-18 Affibody Ab Neonatal Fc receptor binding dimer and methods of use
WO2016065323A2 (fr) 2014-10-23 2016-04-28 Singh Biotechnology, Llc Anticorps à domaine unique dirigés contre des antigènes intracellulaires
US10676526B2 (en) 2015-01-30 2020-06-09 Momenta Pharmaceuticals, Inc. FcRn antibodies and methods of use thereof
US10626175B2 (en) 2015-05-12 2020-04-21 Syntimmune, Inc. Humanized affinity matured anti-FcRn antibodies
US10822417B2 (en) 2016-04-25 2020-11-03 Syntimmune, Inc. Humanized affinity matured anti-FcRn antibodies

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
ALAMANOS YDROSOS A.: "Epidemiology of adult rheumatoid arthritis.", AUTOIMMUNITY REVIEWS, vol. 4, no. 3, 2015, pages 130 - 136, XP027686780
ANONYMOUS: "A Study to Evaluate the Nipocalimab and Certolizumab Combination Therapy in Participants With Active Rheumatoid Arthritis (DAISY)", CLINICALTRIALS.GOV, 1 September 2023 (2023-09-01), pages 1 - 16, XP093242192, Retrieved from the Internet <URL:https://clinicaltrials.gov/study/NCT06028438> *
CHOTHIA ET AL., NATURE, vol. 342, 1989, pages 878 - 883
CHOTHIALESK, J. MOL. BIOL., vol. 196, 1987, pages 901 - 917
FELSON ET AL., ARTHRITIS RHEUM., vol. 38, no. 6, 1995, pages 727 - 735
KABAT: "Sequences of Proteins of Immunological Interest", 1991, NATIONAL INSTITUTES OF HEALTH
TAYLOR PETER C ET AL: "Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study", RMD OPEN, vol. 10, no. 2, 7 June 2024 (2024-06-07), pages e004278, XP093242128, ISSN: 2056-5933, DOI: 10.1136/rmdopen-2024-004278 *

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