Compositions and methods for treating rheumatoid arthritis

Abstract

This invention relates to the use of anti-IL6 receptor antibodies as a monotherapy for the treatment of rheumatoid arthritis and for improving the physical function and quality of life of individuals suffering from rheumatoid arthritis.

Description

Technical Field

[0001] [Related Applications] This application claims priority from European Patent Application No. 16305253.3 filed on March 7, 2016, European Patent Application No. 16170664.3 filed on May 20, 2016, and European Patent Application No. 16306111.2 filed on September 5, 2016, each of which is incorporated herein by reference in its entirety. The present invention relates to the field of rheumatoid arthritis. More specifically, the present invention relates to methods for improving physical function in individuals suffering from rheumatoid arthritis, methods for improving health-related qualities in individuals suffering from rheumatoid arthritis, and methods for treating rheumatoid arthritis in individuals suffering from rheumatoid arthritis, comprising administering an anti-IL6 receptor antibody to the individual as monotherapy. Prior Art In North America and Europe, an estimated 0.5% to 1% of the adult population develops rheumatoid arthritis (RA) each year. RA is twice as common in women as in men, with the highest incidence in women over 40 years old. RA is characterized by persistent synovitis and progressive destruction of cartilage and bone in multiple joints. The disease is characterized by symmetrical polyarthritis, primarily affecting the small joints of the hands and feet. The inflammatory process also targets other organs, primarily the bone marrow (anemia), eyes (scleritis, ectopic scleritis), lungs (interstitial pneumonia, pleuritis), heart (pericarditis), and skin (nodules, leukocytoclastic vasculitis). Systemic inflammation is characterized by laboratory abnormalities such as anemia, increased erythrocyte sedimentation rate, fibrinogen, and C-reactive protein (CRP), and clinical symptoms, including fatigue, weight loss, and muscle atrophy in the affected joints. The presence of multiple high-titer rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies provides evidence of immune dysregulation. An estimated 65% to 70% of patients with RA experience progressive disease, leading to joint destruction, disability, and premature death. In addition to improving RA patients' clinical symptoms, there is growing interest in improving their physical function and health-related quality of life. In addition to conventional instruments designed to assess a patient's health status (with or without disease), clinicians and clinical staff have developed new instruments to measure physical function and quality of life. These parameters are useful for clinicians to assess their patients' overall response to specific treatments. For example, by asking patients what their health conditions prevent them from doing and their emotional reactions to these limitations, quality of life extends beyond the continuum of disability / incapacity and handicap. Quality of life also reflects the impact of an individual's personal, social, and economic resources and how these interact with health status (British Journal of Rheumatology 1997;36:884-888). Assessments of physical function in RA patients typically include upper limb fine motor skills, lower limb motor activities, and activities involving both upper and lower limbs. These parameters are now widely used by clinicians, clinical staff, and regulatory agencies to compare different treatment options for RA patients. In some cases, two treatments with similar efficacy characteristics may have different quality of life or physical function improvement profiles. Summary of the Invention The inventors of the present invention have demonstrated that anti-IL6 receptor antibodies administered as monotherapy can show significant efficacy in treating RA and can also significantly improve physical function and quality of life in individuals suffering from RA. The specific examples of the present invention are listed below: Specific example 1 A method of improving physical function in a subject suffering from rheumatoid arthritis, comprising administering to the subject an antibody, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously at 150 mg or 200 mg every two weeks. - The subject is not taking any other disease-modifying antirheumatic drugs (DMARDs) during the administration of the antibody, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 2 The method of embodiment 1, wherein after at least 24 weeks of administration of the antibody, the subject achieves a change from baseline (BL) of at least 0.22 in the Health Assessment Questionnaire Disability Index (HAQ-DI). Specific example 3 The method of embodiment 1 or 2, wherein the subject achieves a change from baseline (BL) of at least 0.30 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 4 The method of any one of embodiments 1 to 3, wherein the subject achieves a change from baseline (BL) of at least 0.4 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 5 The method of any one of embodiments 1 to 4, wherein the subject achieves a change from baseline (BL) of at least 0.50 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 6 The method of any one of embodiments 1 to 5, wherein the subject achieves a change from baseline (BL) of at least 0.60 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 7 The method of any one of embodiments 1 to 6, wherein the subject achieves a change from baseline (BL) in the Health Assessment Questionnaire Disability Index (HAQ-DI) of at least 0.61 after at least 24 weeks of administration of the antibody. Specific example 8 A method of improving the health-related quality of life of a subject suffering from rheumatoid arthritis, comprising administering to the subject an antibody, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously at 150 mg or 200 mg every two weeks. - The subject is not taking any other disease-modifying antirheumatic drugs (DMARDs) during the administration of the antibody, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 9 The method of embodiment 8, wherein the subject achieves a change from baseline (BL) of at least 2.5 on the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 10 The method of embodiment 8 or 9, wherein the subject achieves a change from baseline (BL) of at least 3 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 11 The method of any one of embodiments 8 to 10, wherein the subject achieves a change from baseline (BL) of at least 4 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 12 The method of any one of embodiments 8 to 11, wherein the subject achieves a change from baseline (BL) of at least 5 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 13 The method of any one of embodiments 8 to 12, wherein the subject achieves a change from baseline (BL) of at least 6 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 14 The method of any one of embodiments 8 to 13, wherein the subject achieves a change from baseline (BL) of at least 7 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 15 The method of any one of embodiments 8 to 14, wherein the subject achieves a change from baseline (BL) of at least 8 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 16 The method of any one of embodiments 8 to 15, wherein the subject achieves a change from baseline (BL) of at least 8.74 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 17 A method of treating rheumatoid arthritis in a subject, comprising administering to the subject an antibody, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously at 150 mg or 200 mg every two weeks. - The subject is not taking any other disease-modifying antirheumatic drugs (DMARDs) during the administration of the antibody, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 18 The method of embodiment 17, wherein the subject achieves a 20% improvement (ACR20) in the American College of Rheumatology core set disease index at least 24 weeks after administration of the antibody. Specific example 19 The method of embodiment 17 or 18, wherein the subject achieves a 50% improvement in an American College of Rheumatology core panel disease indicator (ACR50) at least 24 weeks after administration of the antibody. Specific example 20 The method of any one of embodiments 17 to 19, wherein the subject achieves a 70% improvement (ACR70) in an American College of Rheumatology core panel disease indicator at least 24 weeks after administration of the antibody. Specific example 21 The method of any one of embodiments 17 to 20, wherein the subject achieves a change from baseline (BL) of at least 2 in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) after at least 24 weeks of administration of the antibody. Specific example 22 The method of any one of embodiments 17 to 21, wherein the subject achieves a change from baseline (BL) of at least 2.5 in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) after at least 24 weeks of administration of the antibody. Specific example 23 The method of any one of embodiments 17 to 22, wherein the subject achieves a change from baseline (BL) in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) of at least 3, at least 3.2, or about 3.28 after administration of the antibody for at least 24 weeks. Specific example 24 The method of any one of embodiments 17 to 23, wherein the subject achieves a DAS28-ESR score of less than 3.2 after at least 24 weeks of administration of the antibody. Specific example 25 The method of any one of embodiments 17 to 23, wherein the subject achieves a DAS28-ESR score of less than 2.6 after at least 24 weeks of administration of the antibody. Specific example 26 The method of any one of Embodiments 1 to 25, wherein the subject whose rheumatoid arthritis has not been effectively treated with one or more disease-modifying antirheumatic drugs (DMARDs) other than antibodies is a subject who has had an inadequate response or is intolerant to one or more DMARDs. Specific example 27 The method of any one of Embodiments 1 to 26, wherein the subject whose rheumatoid arthritis has not responded to prior treatment with at least one DMARD other than an antibody is a subject whose rheumatoid arthritis has not responded to prior treatment with methotrexate. Specific example 28 The method of any one of Embodiments 1 to 27, wherein the subject whose rheumatoid arthritis has not been effectively treated with one or more DMARDs other than an antibody is a subject who has had an inadequate response to or is intolerant to methotrexate. Specific example 29 The method of any one of Embodiments 1 to 28, wherein the subject suffering from rheumatoid arthritis is a subject suffering from moderately to severely active rheumatoid arthritis. Specific example 30 The method of any one of Embodiments 1 to 29, wherein the antibody is administered using a prefilled syringe. Specific example 31 The method of any one of Embodiments 1 to 30, wherein the antibody is administered using an automatic injector. Specific example 32 The method of any one of Embodiments 1 to 31, wherein the antibody is administered in a pH 6.0 buffered aqueous solution containing 21 mM histidine, 45 mM arginine, 0.2% (w / v) polysorbate 20, and 5% (w / v) sucrose. Specific example 33 The method of embodiment 32, wherein the solution comprises at least 130 mg / mL antibody. Specific example 34 The method of embodiment 32, wherein the solution comprises 131.6 mg / mL antibody. Specific example 35 The method of embodiment 32, wherein the solution comprises 175 mg / mL antibody. Specific example 36 The method of any one of embodiments 1 to 35, wherein the antibody (comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 1 and a light chain variable region comprising the sequence of SEQ ID NO: 2) is sarilumab. Specific example 37 An antibody for use in a method of improving physical function in an individual suffering from rheumatoid arthritis, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously to the subject at 150 mg or 200 mg every two weeks, - The subject is not taking any other disease-modifying antirheumatic drugs (DMARDs) during the administration of the antibody, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 38 The antibody for use in embodiment 37, wherein the subject achieves a change from baseline (BL) of at least 0.22 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 39 The antibody for use in embodiment 37 or 38, wherein the subject achieves a change from baseline (BL) of at least 0.30 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 40 The antibody for use in any one of embodiments 37 to 39, wherein the subject achieves a change from baseline (BL) of at least 0.4 in the Health Assessment Questionnaire Disability Index (HAQ-DI) after at least 24 weeks of administration of the antibody. Specific example 41 The antibody for use in any one of embodiments 37 to 40, wherein the subject achieves a change from baseline (BL) in the Health Assessment Questionnaire Disability Index (HAQ-DI) of at least 0.50 after at least 24 weeks of administration of the antibody. Specific example 42 The antibody for use in any one of embodiments 37 to 41, wherein the subject achieves a change from baseline (BL) in the Health Assessment Questionnaire Disability Index (HAQ-DI) of at least 0.60 after at least 24 weeks of administration of the antibody. Specific example 43 The antibody for use in any one of embodiments 37 to 42, wherein the subject achieves a change from baseline (BL) in the Health Assessment Questionnaire Disability Index (HAQ-DI) of at least 0.61 after at least 24 weeks of administration of the antibody. Specific example 44 An antibody for use in a method of improving health-related quality of life in an individual suffering from rheumatoid arthritis, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously to the subject at 150 mg or 200 mg every two weeks, - The subject is not taking any other disease-modifying antirheumatic drugs (DMARDs) during the administration of the antibody, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 45 The antibody for use in embodiment 44, wherein the subject achieves a change from baseline (BL) of at least 2.5 on the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 46 The antibody for use in embodiment 44 or 45, wherein the subject achieves a change from baseline (BL) of at least 3 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 47 The antibody for use in any one of embodiments 44 to 46, wherein the subject achieves a change from baseline (BL) of at least 4 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 48 The antibody for use in any one of embodiments 44 to 47, wherein the subject achieves a change from baseline (BL) of at least 5 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 49 The antibody for use in any one of embodiments 44 to 48, wherein the subject achieves a change from baseline (BL) of at least 6 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 50 The antibody for use in any one of embodiments 44 to 49, wherein the subject achieves a change from baseline (BL) of at least 7 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 51 The antibody for use in any one of embodiments 44 to 50, wherein the subject achieves a change from baseline (BL) of at least 8 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 52 The antibody for use in any one of embodiments 44 to 51, wherein the subject achieves a change from baseline (BL) of 8.74 in the Short Form-36 Body Component Scale (SF-36 PCS) after at least 24 weeks of administration of the antibody. Specific example 53 An antibody for use in a method of treating rheumatoid arthritis in a subject, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously to the subject at 150 mg or 200 mg every two weeks, - The subject is not taking any other disease-modifying antirheumatic drugs (DMARDs) during the administration of the antibody, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 54 The antibody for use in embodiment 53, wherein the subject achieves a 20% improvement in an American College of Rheumatology core panel disease control score (ACR20) at least 24 weeks after administration of the antibody. Specific example 55 The antibody for use in embodiment 53 or 54, wherein the subject achieves a 50% improvement in an American College of Rheumatology core panel disease indicator (ACR50) at least 24 weeks after administration of the antibody. Specific example 56 The antibody for use in any one of embodiments 53 to 55, wherein the subject achieves a 70% improvement in an American College of Rheumatology core panel disease indicator (ACR70) at least 24 weeks after administration of the antibody. Specific example 57 The antibody for use in any one of embodiments 53 to 56, wherein the subject achieves a change from baseline (BL) of at least 2 in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) after at least 24 weeks of administration of the antibody. Specific example 58 The antibody for use in any one of embodiments 53 to 57, wherein the subject achieves a change from baseline (BL) of at least 2.5 in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) after at least 24 weeks of administration of the antibody. Specific example 59 The antibody for use in any one of embodiments 53 to 58, wherein the subject achieves a change from baseline (BL) in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) of at least 3, at least 3.2, or about 3.28 after at least 24 weeks of administration of the antibody. Specific example 60 The antibody for use in any one of embodiments 53 to 59, wherein the subject achieves a DAS28-ESR score of less than 3.2 after at least 24 weeks of administration of the antibody. Specific example 61 The antibody for use in any one of embodiments 53 to 60, wherein the subject achieves a DAS28-ESR score of less than 2.6 after at least 24 weeks of administration of the antibody. Specific example 62 The antibody for use in any one of Embodiments 37 to 61, wherein the subject whose rheumatoid arthritis has not been effectively treated with one or more disease-modifying antirheumatic drugs (DMARDs) other than the antibody is a subject who has had an inadequate response or is intolerant to one or more DMARDs. Specific example 63 The antibody for use in any one of embodiments 37 to 62, wherein the subject whose rheumatoid arthritis has not responded to prior treatment with at least one DMARD other than the antibody is a subject whose rheumatoid arthritis has not responded to prior treatment with methotrexate. Specific example 64 The antibody for use in any one of Embodiments 37 to 63, wherein the subject whose rheumatoid arthritis has not been effectively treated with one or more DMARDs other than the antibody is a subject who has had an inadequate response to or is intolerant to methotrexate. Specific example 65 The antibody for use in any one of Embodiments 37 to 64, wherein the subject suffering from rheumatoid arthritis is a subject suffering from moderately active rheumatoid arthritis to severely active rheumatoid arthritis. Specific example 66 The antibody for use in any one of Embodiments 37 to 65, wherein the antibody is administered using a pre-filled syringe. Specific example 67 The antibody for use in any one of Embodiments 37 to 66, wherein the antibody is administered using an automatic injector. Specific example 68 The antibody for use in any one of embodiments 37 to 67, wherein the antibody is administered in a pH 6.0 buffered aqueous solution containing 21 mM histidine, 45 mM arginine, 0.2% (w / v) polysorbate 20, and 5% (w / v) sucrose. Specific example 69 The antibody for use in embodiment 68, wherein the solution comprises at least 130 mg / mL of antibody. Specific example 70 The antibody used in embodiment 68, wherein the solution contains 131.6 mg / mL antibody. Specific example 71 The antibody used in embodiment 68, wherein the solution comprises 175 mg / mL of antibody. Specific example 72 The antibody for use in any one of embodiments 37 to 71, wherein the antibody (comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 1 and a light chain variable region comprising the sequence of SEQ ID NO: 2) is sarizumab. Specific example 73 The antibody for use in any one of Embodiments 37 to 72, wherein the antibody is administered to the subject subcutaneously at 150 mg once every two weeks. Specific example 74 The antibody for use in any one of Embodiments 37 to 72, wherein the antibody is administered to the subject subcutaneously at 200 mg once every two weeks. Specific example 75 The antibody for use in any of the preceding embodiments, wherein the subject is intolerant to one or more DMARDs. Specific example 76 The antibody for use in embodiment 75, wherein the DMARD is methotrexate. Specific example 77 The antibody for use in any of the preceding embodiments, wherein the subject has moderately to severely active rheumatoid arthritis and has an inadequate response to or intolerance to disease-modifying antirheumatic drugs. Specific example 78 The antibody for use in embodiment 77, wherein the DMARD is methotrexate. Specific example 79 The antibody for use in any of the preceding embodiments, wherein the individual suffers from a reduced quality of life due to RA. Specific examples 80 The antibody for use in embodiment 77, wherein the subject scores worse than the mean of a metric selected from the group consisting of: change from baseline in the European Quality of Life Five Dimensions Level 3 (EQ-5D-3L), change from baseline in the Rheumatoid Arthritis Disease Impact Index (RAID), work days lost due to arthritis, decreased work productivity due to arthritis 50%, arthritis interference with work productivity, days lost from home work due to arthritis, reduced productivity in housework due to arthritis 50% of days, days missed from home / social / leisure activities due to arthritis, days hired for outside help due to arthritis, rate of RA interference with housework productivity, morning stiffness VAS, individual ACR facets - TJC and SJC, individual ACR facets - clinician global VAS, participant global VAS and pain VAS, and individual ACR facets - ESR content. Specific example 81 The antibody for use in any of the preceding embodiments, wherein the antibody is administered subcutaneously to the subject at 150 mg once every two weeks. Specific example 82 The antibody for use in any one of Embodiments 37 to 80, wherein the antibody is administered to the subject subcutaneously at 200 mg once every two weeks. Specific example 83 A composition comprising the antibody of any one of embodiments 37 to 82. Specific example 84 Use of an antibody for the manufacture of a medicament for improving physical function in an individual suffering from rheumatoid arthritis, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously at 150 mg or 200 mg every two weeks. - The subject is not given any other DMARDs during the course of the antibody administration, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 85 Use of an antibody for the manufacture of a medicament for improving the health-related quality of life of an individual suffering from rheumatoid arthritis, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously at 150 mg or 200 mg every two weeks. - The subject is not given any other DMARDs during the course of the antibody administration, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Specific example 86 Use of an antibody for the manufacture of a medicament for treating rheumatoid arthritis in a subject, wherein: - The antibody comprises a heavy chain variable region comprising the sequence of SEQ ID NO: 1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, - Administer the antibody subcutaneously at 150 mg or 200 mg every two weeks. - The subject is not given any other DMARDs during the course of the antibody administration, and - The individual has previously been treated with at least one DMARD other than the antibody for rheumatoid arthritis that was ineffective. Implementation Method The inventors have demonstrated that anti-IL6R antibodies administered as monotherapy are effective in treating rheumatoid arthritis. Furthermore, the inventors have demonstrated that the antibodies administered as monotherapy are also effective in improving physical function and quality of life in individuals with rheumatoid arthritis. According to the present invention, "monotherapy" means that the subject receiving the antibody is not administered any other DMARD during the course of administration of the antibody. The efficacy of antibodies used to treat rheumatoid arthritis is typically measured using standard methods commonly used by clinicians and rheumatologists in the art, such as the DAS-28 and ACR parameters, such as the DAS-28 ESR, ACR20, ACR50, and ACR70 parameters. In various embodiments, improvement in physical function in individuals with rheumatoid arthritis is measured using a standard method commonly used in the art by clinicians and rheumatologists, namely the HAQ-DI parameter. Improvement in quality of life in individuals with rheumatoid arthritis is typically measured using standard methods commonly used in the art by clinicians and rheumatologists, such as the SF36 parameters, and in some embodiments, the SF-36 PCS parameters. Baseline (also referred to herein as "BL") is defined as the score obtained from a subject prior to administration of an antibody of the invention. The change from baseline is defined as the difference between the subject's score at baseline and the subject's score following administration of an antibody of the invention (e.g., measured at least 24 weeks after the first administration of the antibody, including 24 weeks after the first administration of the antibody). [DAS28-ESR] The DAS28 is a composite score consisting of four variables: - Number of tender joints (based on 28 joints: shoulder (n=2), elbow (n=2), wrist (n=2), metacarpophalangeal (n=10), thumb interphalangeal (n=2), proximal interphalangeal (n=8), knee (n=2)) - Number of swollen joints (based on 28 joints: shoulder (n=2), elbow (n=2), wrist (n=2), metacarpophalangeal (n=10), thumb interphalangeal (n=2), proximal interphalangeal (n=8), knee (n=2)) - Patient's global health (GH) assessed by the ACR RA core group questionnaire (Patient Global Assessment), presented on a 100mm visual analogue scale (VAS) - Inflammatory markers assessed by CRP (in mg / L) or ESR (in mm / hr). The DAS28 is a continuous measure that can measure both the absolute change in disease activity and the percentage improvement. The DAS28-ESR can be calculated using the following formula: The DAS28-ESR score provides a single number that indicates the current disease activity of RA. A DAS28-ESR score over 5.1 indicates high disease activity, while a DAS28-ESR score below 3.2 indicates low disease activity, and a DAS28-ESR score below 2.6 indicates remission. When calculating 28TJC and 28SJC, if missing individual joint scores (i.e., joints that have undergone replacement or fusion are not considered for swelling or tenderness) are imputed as the average of the scored joints, the tender / swollen joint count is calculated as follows: 28TJC / 28SJC = sum (score tender / swollen joints) * (number of joints in the total joint group / number of scored tender / swollen joints). The total joint group number is defined as (28 - number of joints replaced or fused), and the scored joints refer to the number of joints with a response (0 - no pain, 1 - pain). If the individual responds that they have not experienced pain (ie, ESR = 0), then for the purpose of calculating the DAS-ESR score, the value ESR = 1 should be inserted for the DAS28-ESR calculation so that the non-missing score can be used. If one of the facets is missing, DAS28-ESR is considered to be missing. [Visual Analog Score (VAS)] The VAS is a measure that assesses the severity of a patient's rheumatoid arthritis. Patients make a vertical mark on each side of the two lines that best describes the amount of pain they experience due to their rheumatoid arthritis. The scale ranges from no pain to worst pain. ACR20 To be classified as an ACR20 responder, patients had to achieve a 20% improvement from baseline in both the TJC and SJC and a 20% improvement in at least three of the remaining five ACR domains: clinician's global assessment of disease activity, patient's global assessment of disease activity, pain, HAQ-DI, and CRP. ACR50 ACR50 was defined as an event with at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least three of the other five ACR dimensions. ACR70 ACR50 was defined as an event with at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least three of the other five ACR dimensions. The seven ACR facets for assessing RA signs and symptoms are defined below (AG): A) Tender joint count (TJC) A total of 68 joints were assessed for tenderness. The 68 joints examined for tenderness were: temporomandibular (n=2), sternoclavicular (n=2), acromioclavicular (n=2), shoulder (n=2), elbow (n=2), wrist (n=2), metacarpophalangeal (n=10), thumb interphalangeal (n=2), distal interphalangeal (n=8), proximal interphalangeal (n=8), hip (n=2), knee (n=2), ankle (n=2), tarsal (n=2), metatarsophalangeal (n=10), great toe interphalangeal (n=2), and proximal / distal toe interphalangeal (n=8). A formal joint count was performed by trained assessors. Joint tenderness was defined as pain elicited by pressure applied to the joint by the assessor's thumb and index finger. The assessor categorized each joint as painful (yes / no) and swollen (yes / no). Each tender joint was scored 0 / 1, with 0 indicating no pain and 1 indicating pain. The number of tender joints ranged from 0 to 68, with 0 considered the best and 68 the worst. B) Swollen joint count (SJC) The 66 joints tested for swelling are the same as those tested for tenderness, except that the hip joint is excluded. A formal joint count is performed by a trained assessor. The assessor categorizes each joint as swollen (yes / no). Each swollen joint is assigned a score of 0 / 1, where 0 indicates no swelling and 1 indicates a swollen joint. The number of swollen joints ranges from 0 to 66, with 0 considered the best and 66 the worst. C) Clinician's Global Assessment of Disease Activity The clinician's global assessment of the patient's current disease activity was based on a fixed 100-mm horizontal VAS, where 0 was considered the best disease activity (no disease activity) and 100 the worst (maximum disease activity). D) Patient's global assessment of disease activity The patient's global assessment of current disease activity was assessed using a fixed 100-mm horizontal VAS, where 0 was considered the best disease activity (no disease activity) and 100 the worst (maximum disease activity). E) Patient pain assessment Patients were asked to indicate the intensity of their pain due to RA using a 100-mm horizontal VAS, where 0 was considered "no pain" and 100 was considered "the worst pain you can imagine." F) Patient's physical function assessment - Health Assessment Questionnaire Disease Index (HAQ-DI) The HAQ-DI is a standardized questionnaire developed for RA. Using the past week as a timeframe, the HAQ-DI focuses on whether the respondent is able to perform activities and covers 20 items across eight categories: dressing and grooming, rising, eating, walking, hygiene, reaching, grasping, and mobility, with at least two questions in each category. The HAQ-DI's four responses are graded as follows: no difficulty = 0; some difficulty = 1; significant difficulty = 2; and unable to do = 3. To calculate the standard HAQ-DI score (using assistive devices / devices), there are three steps: 1. Sum the scores for each of the 8 categories by using the highest subcategory score within each category. For example, the category "eating" has 3 subcategory items. If the patient responds 1, 2, and 0, the category score is 2. 2. If indicated, use aids / equipment and / or get help from others to make adjustments. - Adjust category scores by increasing from 0 or 1 to 2. - If the patient's highest score in that subcategory is 2, maintain it at 2; if it is 3, maintain it at 3. - Data entered in the "Other Designations" field is not used for score adjustments. 3. Divide the total category score by the number of categories responded to (must be at least 6) to obtain a HAQ-DI score ranging from 0 to 3 (3 = worst functioning). When fewer than six of the eight categories are scored, the HAQ-DI score cannot be calculated effectively. HAQ-DI scores range from 0 to 3. A high HAQ-DI score has been found to be a strong predictor of morbidity and mortality in RA. A difference of 0.22 units is considered clinically significant. G) Acute phase reactant levels measured by CRP High-sensitivity CRP was assessed intermediately. Because CRP levels are directly correlated with interleukin-6 (IL-6) receptor activity, the active dose regimen was expected to significantly reduce CRP levels. Therefore, post-dose CRP levels remained blinded to the investigators, sponsor, and patients during the study. The ACR facets are further described in Table 1. TJC: Total joint count, SJC: Swollen joint count, VAS: Visual analog scale SF-36 V2 The QualityMetric SF-36v2® Health Survey is a multi-purpose, short-form health survey with 36 questions. It generates scores for eight domains (physical functioning, role physical, bodily pain, overall health, vitality, social functioning, role emotional, and mental health, each scored from 0 to 100, with higher scores indicating greater health and well-being), as well as two composite measures of physical and mental health: the Physical Component Score (PCS) and the Mental Component Score (MCS). The scoring process is summarized as follows: 1. Enter project response data. 2. Recode item response values. 3. Determine the raw score of the health zone scale. 4. Convert the raw scores of the health zone scale into a score ranging from 0 to 100. 5. Convert the health zone scale of 0 to 100 to a routine-based score. 6. Score the PCS and MCS measurements. The following table shows the composition and overall assessment of the SF-36 scale: *MCS and PCS derived from eight scales (Ware, JE. et al. 1994 "SF-36 Physical and Mental Health Summary Scales: A Users' Manual". Boston: The Health Institute) The abbreviated items are as follows: 3a vigorous activity, such as running, lifting heavy objects, or participating in vigorous sports; 3b moderate activity, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf; 3c lifting or carrying rubbish; 3d climbing several flights of stairs; 3e climbing one flight of stairs; 3f bending, kneeling, or stooping; 3g walking more than a mile; 3h walking several hundred yards; 3i walking one hundred yards; 3j bathing or dressing oneself; 4a reducing the amount of time spent on work or other activities; 4b achieving less than you would like; 4c limited types of work or other activities; 4d having difficulty doing work or other activities (e.g., having to make an extra effort); 7 intensity of body pain; 8 pain level interfering with normal work; 1 How is your health: excellent, very good, good, fair, poor; 11a seem to be getting sick more often than other people; 11b as healthy as anyone I know; 11c expect my health to be worse; 11d very good health; 9a feeling energetic; 9e Full of energy; 9g Feeling very tired; 9i Feeling fatigued; 6 The extent of health problems interfering with normal social activities; 10 The frequency of health problems interfering with social activities; 5a Reducing the amount of time spent on work or other activities; 5b Achieving less than you wanted; 5c Being more careless than usual at work or other activities; 9b Being very nervous; 9c Feeling down and that nothing can cheer you up; 9d Feeling calm and peaceful; 9f Feeling listless and depressed; and 9h Feeling happy. PCS and MCS summary measures are calculated if at least 50% of the facet scales are available. Scale scores are calculated if at least 50% of the items in the corresponding scale are available. Missing items are imputed by averaging the available items. Overall scoring information Record items and scales in 3 steps; ˙Step 1. Item recoding. 10 items need to be recoded. Step 2. Calculate the scale score by summing the items in the same scale (raw scale score); and ˙Step 3. Convert the original scale scores to a 0-100 scale (converted scale). Project Recoding Before assigning final item values, check all 36 items for out-of-range values. All out-of-range values ​​should be recoded as missing data. The following table shows the recoded response options. How to handle missing data A scale score is calculated if the respondent answers at least half of the items in a multi-item scale (or half plus one in the case of a scale with an odd number of items). When a respondent answers at least 50% of the scale's items, a recommended algorithm replaces the individual's specific estimate for the missing items. A psychometrically sound estimate is the average score across all completed items on the same scale for that respondent. For example, if a respondent leaves one item blank on a five-item mental health scale, the respondent's average score (across all four completed mental health items) should be used to replace that item. When estimating a respondent's average score, use the respondent's last item value. Calculate the original scale score After item recoding (including handling of missing data), a raw score was calculated for each scale. This score is the simple algebraic sum of the responses to all items in that scale. If a respondent answered at least 50% of the items on a multi-item scale, a score was calculated. If a respondent did not answer at least 50% of the items, the score for that scale was set to missing. Conversion of scale scores The next step involves converting each raw score to a 0 to 100 scale using the following formula: Conversion scale = [(actual raw score - lowest possible raw score) / possible raw score range] x 100 This conversion converts the lowest and highest possible scores to zero and 100 respectively. Scores for each of the 36 items were collected on the CRF (Case Report Form). SAS (Statistical Analysis System) code (e.g., by the QualityMetric survey provider) was then used to calculate eight scales, two summary measure scores, and a standardized summary score. PCS and MCS summary measures are calculated if at least 50% of the facet scales are available. Scale scores are calculated if at least 50% of the items in the corresponding scale are available. Missing items are imputed by averaging the available items. Then, the changes in SF-36 scores relative to BL were analyzed (physical component and psychological component scores with eight domains). SF-36 V2 Scoring General Scoring Information: Score the items and scale in 3 steps (as instructed in the QualityMetric survey manual): Step 1. Item recoding, 10 items need to be recoded, Step 2. Calculate the scale score by summing the items of the same scale (raw scale score); and Step 3. Convert the original scale scores to a 0-100 scale (converted scale). Step 5: Calculate the Z score Step 6: Convert Z-scores to area-based conventional scores PCS: Calculates the aggregate PCS score using a specific weighted formula and converts it into a conventional score. MCS: Use a specific weighted formula to calculate the collective MCS score and convert it into a conventional score Project Recoding Before assigning final item values, check all 36 items for out-of-range values. All out-of-range values ​​should be recoded as missing data. How to handle missing data A scale score is calculated if the respondent answers at least half of the items in a multi-item scale (or half plus one in the case of a scale with an odd number of items). When a respondent answers at least 50% of the scale's items, a recommended algorithm replaces the individual's specific estimate for the missing items. A psychometrically sound estimate is the average score across all completed items on the same scale for that respondent. For example, if a respondent leaves one item blank on a five-item mental health scale, the respondent's average score (across all four completed mental health items) should be used to replace that item. When estimating a respondent's average score, use the respondent's last item value. Calculate the original scale score After item recoding (including handling of missing data), a raw score was calculated for each scale. This score is the simple algebraic sum of the responses to all items in that scale. If a respondent answered at least 50% of the items on a multi-item scale, a score was calculated. If a respondent did not answer at least 50% of the items, the score for that scale was set to missing. Conversion of scale scores The next step involves converting each raw score to a 0 to 100 scale using the following formula: Conversion scale = [(actual raw score - lowest possible raw score) / possible raw score range] x 100 This conversion converts the lowest and highest possible scores to zero and 100 respectively. [Antibody] The present disclosure includes methods comprising administering to a patient an antibody or antigen-binding fragment thereof that specifically binds to hIL-6R. As used herein, the term "hIL-6R" refers to a human interleukin receptor that specifically binds to human interleukin-6 (IL-6). In certain embodiments, the antibody administered to the patient specifically binds to the extracellular domain of hIL-6R. The term "antibody," as used herein, is intended to refer to immunoglobulin molecules comprising four polypeptide chains: two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, as well as aggregates thereof (e.g., IgM). Each heavy chain comprises a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region. The heavy chain constant region comprises three domains: CH1, CH2, and CH3. Each light chain comprises a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region comprises one domain (CL1). The VH and VL regions are further divided into regions of hypervariability, termed complementarity-determining regions (CDRs), interspersed with more conserved regions, termed framework regions (FRs). Each VH and VL region is composed of three CDRs and four FRs, arranged from amino-terminus to carboxyl-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. In some embodiments, the FRs of an antibody (or antigen-binding portion thereof) may be identical to human germline sequences or may be naturally or artificially modified. Consensus amino acid sequences can be defined based on concurrent analysis of two or more CDRs. As used herein, the term "antibody" also includes antigen-binding fragments of intact antibody molecules. The terms "antigen-binding portion" of an antibody, "antigen-binding fragment" of an antibody, and the like include any naturally occurring, enzymatically derived, synthetic, or genetically engineered polypeptide or glycoprotein that specifically binds to an antigen to form a complex. Antigen-binding fragments of an antibody can be derived, for example, from intact antibody molecules using any suitable standard technique, such as proteolytic digestion or recombinant genetic engineering techniques involving the manipulation and expression of DNA encoding antibody variable and, optionally, constant domains. Such DNA is known and / or readily available from, for example, commercial sources, DNA libraries (including, for example, phage antibody libraries), or can be synthesized. The DNA can be sequenced and manipulated chemically or using molecular biology techniques, for example, to arrange one or more variable and / or constant domains into an appropriate configuration, or to introduce codons, generate cysteine ​​residues, modify, add, or delete amino acids. Non-limiting examples of antigen-binding fragments include: (i) Fab fragments; (ii) F(ab')2 fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single-chain Fv (scFv) molecules; (vi) dAb fragments; and (vii) minimal recognition units composed of amino acid residues that mimic the hypervariable region of an antibody (e.g., isolated complementarity-determining regions (CDRs), such as CDR3 peptides), or constrained FR3-CDR3-FR4 peptides. Other engineered molecules (such as domain-specific antibodies, single-domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-grafted antibodies, diabodies, triabodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies, bivalent nanobodies, etc.), small modulatory molecule immunopharmaceuticals (SMIPs), and shark variable IgNAR domains) are also encompassed by the term "antigen-binding fragment" as used herein. Antigen-binding fragments of antibodies typically contain at least one variable domain. The variable domain can be of any size and amino acid composition and generally contains at least one CDR adjacent to or in frame with one or more framework sequences. In antigen-binding fragments comprising a VH domain associated with a VL domain, the VH and VL domains can be positioned relative to one another in any suitable arrangement. For example, the variable region is a dimer and contains VH-VH, VH-VL, or VL-VL dimers. Alternatively, an antigen-binding fragment of an antibody may contain a monomeric VH or VL domain. In certain embodiments, an antigen-binding fragment of an antibody may contain at least one variable domain covalently linked to at least one constant domain. Non-limiting exemplary configurations of variable and constant domains that may be found in an antigen-binding fragment of an antibody include: (i) VH-CH1; (ii) VH-CH2; (iii) VH-CH3; (iv) VH-CH1-CH2; (v) VH-CH1-CH2-CH3; (vi) VH-CH2-CH3; (vii) VH-CL; (viii) VL-CH1; (ix) VL-CH2; (x) VL-CH3; (xi) VL-CH1-CH2; (xii) VL-CH1-CH2-CH3; (xiii) VL-CH2-CH3; and (xiv) VL-CL. In any configuration of the variable and constant domains (including any of the exemplary configurations listed above), the variable and constant domains may be directly linked to each other or linked by a complete or partial hub or linker region. In various embodiments, the hub region is composed of at least two (e.g., 5, 10, 15, 20, 40, 60, or more) amino acids that create a flexible or semi-flexible linkage between adjacent variable and / or constant domains in a single polypeptide molecule. Furthermore, in various embodiments, an antigen-binding fragment of an antibody may comprise any of the variable and constant domain configurations listed above and / or a homodimer or heterodimer (or other aggregate) formed in non-covalent association (e.g., via disulfide bonds, etc.) with one or more monomeric VH or VL domains. As with full antibody molecules, antigen-binding fragments can be monospecific or multispecific (e.g., bispecific). Multispecific antigen-binding fragments of antibodies typically comprise at least two different variable domains, each of which is capable of specifically binding to a different epitope on a separate antigen or the same antigen. Any multispecific antibody format, including the exemplary bispecific antibody formats disclosed herein, can be adapted for use in an anti-IL-6R antibody antigen-binding fragment using conventional techniques available in the art, in various embodiments. The constant region of an antibody is crucial for the ability of the antibody to fix complement and mediate cell-dependent cytotoxicity. Therefore, the isotype of an antibody can be selected based on whether it is desired that the antibody mediate cytotoxicity. The term "human antibody," as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the invention may, in various embodiments, include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-directed mutagenesis in vitro or by somatic mutagenesis in vivo), for example, in the CDRs and, in some embodiments, in CDR3. However, the term "human antibody," as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species (such as a mouse) have been grafted onto human framework sequences. The term "recombinant human antibody," as used herein, is intended to include all human antibodies produced, expressed, created, or isolated by recombinant means, such as antibodies expressed using recombinant expression vectors transfected into host cells (described further below), antibodies isolated from recombinant, combinatorial human antibody libraries (described further below), antibodies isolated from animals (e.g., mice) that are transgenic for human immunoglobulin genes (see, e.g., Taylor et al. (1992) Nucl. Acids Res. 20:6287-6295, incorporated herein by reference in its entirety), or antibodies produced, expressed, created, or isolated by any other means involving splicing human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. However, in certain embodiments, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when animals transgenic for human Ig sequences are used, in vivo somatic mutagenesis), and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies, while derived from and related to human germline VH and VL sequences, may not be sequences that naturally exist in the human antibody germline repertoire in vivo. Human antibodies exist in two forms related to hub heterogeneity. In one embodiment, the immunoglobulin molecule comprises a stable four-chain structure of approximately 150-160 kDa, in which the dimer is held together by interchain heavy chain disulfide bonds. In another embodiment, the dimer is not linked by interchain disulfide bonds and forms a single molecule of approximately 75-80 kDa composed of covalently coupled light and heavy chains (half-antibodies). These embodiments / forms are very difficult to separate, even after affinity purification. The frequency of the second form in various intact IgG isotypes is due to, but not limited to, structural differences in the hub region of the antibody isotype. In the hub region of the human IgG4 hub, a single amino acid substitution can significantly reduce the occurrence of the second form to levels typically observed with the human IgG1 hub (Angal et al. (1993) Molecular Immunology 30:105). The present invention encompasses, in various embodiments, antibodies with one or more mutations in the CH2 or CH3 hub regions, which may be desirable, for example, to improve the yield of a desired antibody form during manufacture. As used herein, an "isolated antibody" refers to an antibody that has been identified and separated and / or recovered from at least one component of its natural environment. For example, an antibody that has been isolated or removed from at least one component of an organism, or from a tissue or cell in which the antibody naturally occurs or is produced, is an "isolated antibody." In various embodiments, an isolated antibody also includes the antibody in situ within recombinant cells. In other embodiments, an isolated antibody is an antibody that has been subjected to at least one purification or isolation step. In various embodiments, the isolated antibody is substantially free of other cellular material and / or chemicals. The term "specifically binds" or similar terms indicates that the antibody, or antigen-binding fragment thereof, forms a relatively stable complex with the antigen under physiological conditions. Methods for determining whether an antibody specifically binds to an antigen are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like. For example, an antibody that "specifically binds" to IL-6R, as used herein, includes antibodies that bind to IL-6R or a portion thereof with a KD of less than about 1000 nM, less than about 500 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, or about 0.5 nM, as measured by surface plasmon resonance analysis. However, isolated antibodies that specifically bind to human IL-6R may have cross-reactivity to other antigens, such as IL-6R molecules from other (non-human) species. The term "surface plasmon resonance" as used herein refers to an optical phenomenon that allows analysis of real-time interactions by detecting changes in protein concentration in a biosensor matrix, for example using the BIACORE™ system (Biacore Life Sciences division of GE Healthcare, Piscataway, NJ). The term "KD," as used herein, is intended to refer to the equilibrium dissociation constant of an antibody-antigen interaction. The term "epitope" refers to an antigenic determinant that interacts with a specific antigen-binding site in the variable region of an antibody molecule, known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different regions of an antigen and potentially have different biological effects. Epitopes can be conformational or linear. Conformational epitopes are formed by spatially adjacent amino acids in different segments of a linear polypeptide chain. Linear epitopes are formed by adjacent amino acid residues in a polypeptide chain. In some cases, epitopes may include carbohydrate, phosphoyl, or sulfonyl moieties on the antigen. The anti-IL-6R antibodies used in the methods herein may contain one or more amino acid substitutions, insertions, and / or deletions in the framework and / or CDR regions of the heavy and light chain variable domains, compared to the corresponding germline sequences from which the antibodies were derived. Such mutations can be readily identified by comparing the amino acid sequences disclosed herein with germline sequences available, for example, from public antibody sequence databases. Various embodiments of the present invention include methods using antibodies or antigen-binding fragments thereof derived from any of the amino acid sequences disclosed herein, wherein one or more amino acids in the framework and / or CDR regions are mutated to the corresponding residues in the germline sequence from which the antibody was derived, or to the corresponding residues in another human germline sequence, or to conserved amino acid substitutions corresponding to the germline residues (such sequence alterations are collectively referred to herein as "germline mutations"). In certain embodiments, all framework and / or CDR residues in the VH and / or VL domains are mutated back to the residues found in the original germline sequence from which the antibody was derived. In other embodiments, only certain residues are mutated back to the original germline sequence, for example, only the mutated residues found in the first eight amino acids of FR1 or the last eight amino acids of FR4, or only the mutated residues found in CDR1, CDR2, or CDR3. In other embodiments, one or more of the framework and / or CDR residues are mutated to the corresponding residues in a different germline sequence (i.e., a germline sequence different from the germline sequence from which the antibody was originally derived). Furthermore, an antibody may contain any combination of germline mutations in two or more framework and / or CDR regions, for example, where certain individual residues are mutated to the corresponding residues in a particular germline sequence, while certain other residues from the original germline sequence remain unchanged or are mutated to the corresponding residues in a different germline sequence. Once obtained, antibodies and antigen-binding fragments containing one or more germline mutations can be readily tested for one or more desired properties, such as improved binding specificity, increased binding affinity, enhanced or increased antagonistic or agonistic biological properties (as appropriate), reduced immunogenicity, etc. Antibodies and antigen-binding fragments obtained in this general manner are encompassed by the present invention. The present invention also includes methods of using anti-IL-6R antibodies comprising variants of any of the HCVR, LCVR, and / or CDR amino acid sequences disclosed herein having one or more conservative substitutions. For example, the present invention includes the use of anti-IL-6R antibodies having HCVR, LCVR, and / or CDR amino acid sequences having, for example, 10 or fewer, 8 or fewer, 6 or fewer, 4 or fewer, etc., conservative amino acid substitutions relative to any of the HCVR, LCVR, and / or CDR amino acid sequences disclosed herein. According to the present invention, an anti-IL-6R antibody or antigen-binding fragment thereof, in various embodiments, comprises a heavy chain variable region (HCVR), a light chain variable region (LCVR), and / or a complementarity determining region (CDR) comprising any one of the amino acid sequences of an anti-IL-6R antibody as claimed in U.S. Patent No. 7,582,298, which is incorporated herein by reference in its entirety. Anti-IL-6R antibodies or antigen-binding fragments useful in the context of the present methods comprise a heavy chain complementarity determining region (HCDR) of the HCVR comprising the amino acid sequence of SEQ ID NO: 1 and a light chain complementarity determining region (LCDR) of the LCVR comprising the amino acid sequence of SEQ ID NO: 2. According to certain embodiments, an anti-IL-6R antibody or antigen-binding fragment thereof comprises three HCDRs (i.e., HCDR1, HCDR2, and HCDR3) and three LCDRs (i.e., LCDR1, LCDR2, and LCDR3), wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; LCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and LCDR3 comprises the amino acid sequence of SEQ ID NO: 8. In yet other embodiments, an anti-IL-6R antibody or antigen-binding fragment thereof comprises a HCVR comprising SEQ ID NO: 1 and a LCVR comprising SEQ ID NO: 2. In another embodiment, the anti-IL-6R antibody or antigen-binding fragment thereof comprises a heavy chain comprising SEQ ID NO: 9 and a light chain comprising SEQ ID NO: 10. According to certain exemplary embodiments, the methods of the present invention comprise the use of the anti-IL-6R antibody referred to and known in the art as sarulumab, or a bioequivalent thereof. The term "bioequivalence," as used herein, refers to molecules that have similar bioavailability (rate and extent of availability) following administration at the same molar dose and under similar conditions (e.g., the same route of administration), such that the expected efficacy is likely to be substantially the same as that of the comparable molecule in terms of efficacy and safety. Two pharmaceutical compositions comprising an anti-IL-6R antibody are bioequivalent if they are pharmaceutically equivalent, meaning they contain an equivalent amount of the active ingredient (e.g., the IL-6R antibody), are in the same dosage form, are administered by the same route of administration, and meet the same or comparable standards. Bioequivalence can be determined, for example, by comparing the pharmacokinetic parameters of the two compositions in in vivo studies. Common parameters used in bioequivalence studies include peak plasma concentration (Cmax) and the area under the plasma drug concentration-time curve (AUC). In certain embodiments, the present invention relates to a method comprising administering to a subject an antibody comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 1 and a light chain variable region comprising the sequence of SEQ ID NO: 2. The present disclosure provides pharmaceutical compositions comprising these antibodies, and methods of using these compositions. An antibody comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 1 and a light chain variable region comprising the sequence of SEQ ID NO: 2 is an antibody that specifically binds to human interleukin-6 receptor (hIL-6R). See International Publication No. WO 2007 / 143168, which is incorporated herein by reference in its entirety. In one embodiment, the antibody comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 1 and a light chain variable region comprising the sequence of SEQ ID NO: 2 is sarulumab. [DMARD] DMARDs are defined by their use in rheumatoid arthritis to slow disease progression. DMARDs are categorized into synthetic (sDMARDs) and biologic (bDMARDs). Synthetic DMARDs include the non-depleting forms of methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. Biologic DMARDs include the non-depleting forms of adalimumab, golimumab, etanercept, abatacept, infliximab, rituximab, and tocilizumab. [Dosage and Preparation Method] In various embodiments, the antibody is administered to a subject. In various embodiments, the antibody is administered once every two weeks at a dose of about 100 mg, 150 mg, or about 200 mg. "Once every two weeks" is synonymous with "q2w" or "once every two weeks," i.e., the antibody is administered once every two weeks. According to certain embodiments, the antibody is administered subcutaneously. In certain embodiments, about 100 mg, 150 mg, or about 200 mg of the antibody is administered biweekly. In this context, "about" refers to an amount within 5% of the stated amount. For example, "about 100 mg" refers to a range between 95 mg and 105 mg. According to certain embodiments, the antibody is administered subcutaneously. In various embodiments, the antibody is administered to a subject in a formulation comprising suitable carriers, excipients, and other agents that provide enhanced transfer, delivery, tolerability, and the like, and that is suitable for subcutaneous injection. These injectable preparations can be prepared according to known methods. For example, the injectable preparation can be prepared by dissolving, suspending, or emulsifying the above-mentioned antibody or its salt in a conventional sterile aqueous or oily medium for injection. Examples of aqueous media for injection include physiological saline, isotonic solutions containing glucose and other adjuvants, and the like. These can be used in combination with appropriate cosolvents (such as alcohols (e.g., ethanol), polyols (e.g., propylene glycol, polyethylene glycol), and nonionic surfactants (e.g., polysorbate 20 or 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated ramie oil)). Oily media include, for example, sesame oil and soybean oil, and the like, which can be used in combination with cosolvents (such as benzyl benzoate, benzyl alcohol, etc.). The injectable preparation thus prepared is preferably filled into suitable ampoules. Antibodies are generally formulated as described herein and in International Publication No. WO 2011 / 085158, which is incorporated herein by reference in its entirety. In various embodiments, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - About 21mM histidine, - About 45mM arginine, - About 0.2% (w / v) polysorbate 20, - approximately 5% (w / v) sucrose, and - Between about 100 mg / mL and about 200 mg / mL of the antibody. In another embodiment, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - About 21mM histidine, - About 45mM arginine, - About 0.2% (w / v) polysorbate 20, - approximately 5% (w / v) sucrose, and - At least about 130 mg / mL antibody. In another embodiment, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - About 21mM histidine, - About 45mM arginine, - About 0.2% (w / v) polysorbate 20, - approximately 5% (w / v) sucrose, and - Approximately 131.6mg / mL antibody. In another embodiment, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - About 21mM histidine, - About 45mM arginine, - About 0.2% (w / v) polysorbate 20, - approximately 5% (w / v) sucrose, and - Approximately 175mg / mL antibody. In other embodiments, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - 21mM histidine, - 45mM arginine, - 0.2% (w / v) polysorbate 20, - 5% (w / v) sucrose, and - Between 100 mg / mL and about 200 mg / mL of the antibody. In another embodiment, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - 21mM histidine, - 45mM arginine, - 0.2% (w / v) polysorbate 20, - 5% (w / v) sucrose, and - At least 130mg / mL antibody. In another embodiment, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - 21mM histidine, - 45mM arginine, - 0.2% (w / v) polysorbate 20, - 5% (w / v) sucrose, and - 131.6mg / mL antibody. In another embodiment, the antibody is administered in an aqueous buffer solution at about pH 6.0 containing - 21mM histidine, - 45mM arginine, - 0.2% (w / v) polysorbate 20, - 5% (w / v) sucrose, and - 175mg / mL antibody. The antibodies of the present invention can be administered to a subject using any acceptable device or mechanism. For example, this can be achieved using a syringe and needle or using a reusable pen and / or autoinjector delivery device. The methods of the present invention include the use of a variety of reusable pen and / or autoinjector delivery devices to administer the antibodies (or pharmaceutical formulations comprising the antibodies). Examples of such devices include, but are not limited to, AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75 / 25™ pen, HUMALOG™ pen, HUMALIN 70 / 30™ pen (Eli Lilly and Co., Indianapois, IN), NOVOPEN™ I, II, and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, NJ), OPTIPEN™, OPTIPEN PRO™, OPTIPEN STARLET™, and OPTICLIK™ (sanofi-avetis, Frankfurt, Germany), to name a few. Examples of disposable pen and / or autoinjector delivery devices useful for subcutaneous delivery of the pharmaceutical compositions of the present invention include, but are not limited to, the SOLOSTART™ pen (sanofi-aventis), the FLEXPENT™ (Novo Nordisk), and the KWIKPENT™ (Eli Lilly), the SURECLICK™ Autoinjector (Amgen, Thousand Oaks, CA), the PENLET™ (Haselmeier, Stuttgart, Germany), the EPIPEN (Dey, LP), the HUMIRA™ pen (Abbott Labs, Abbott Park, IL), the DAI® autoinjector (SHL Group), and any autoinjector featuring PUSHCLICK™ technology (SHL Group), to name a few. In one embodiment, the antibody is administered using a pre-filled syringe. In another embodiment, the antibody is administered using a prefilled syringe containing a safety system. For example, the safety system prevents accidental needle stick injuries. In a different embodiment, the antibody is administered using a prefilled syringe containing a safety system. Antibodies are administered using a prefilled syringe using the RIS™ safety system (West Pharmaceutical Services Inc.) See also U.S. Patent Nos. 5,215,534 and 9,248,242, which are incorporated herein by reference in their entireties. In another embodiment, the antibody is administered using an autoinjector. In a different embodiment, the antibody is administered using an autoinjector featuring PUSHCLICK™ technology (SHL Group). In different embodiments, an autoinjector is a device comprising a needle that allows for administration of a dose of a composition and / or antibody to a subject. See also U.S. Patent Nos. 9,427,531 and 9,566,395, which are incorporated herein by reference in their entirety. [Patient Group] According to the present invention, "subject" refers to a human subject or a human patient. In various embodiments, the antibodies according to the invention are administered to a subject whose rheumatoid arthritis has been refractory to prior treatment with at least one DMARD other than the antibody. According to the present invention, a subject considered "treatment refractory" by their clinician is, in various embodiments, a subject who has demonstrated intolerance to one or more DMARDs tested by the clinician and / or a subject who has demonstrated an inappropriate response to one or more DMARDs tested by the clinician, and is generally considered by the clinician to still have, or have active, rheumatoid arthritis despite prior administration of one or more DMARDs. "Active rheumatoid arthritis" is generally defined as: - At least 6 swollen joints out of 66 and at least 8 tender joints out of 68, as counted by a clinician in a typical quantitative swollen and tender joint count test, - High-sensitivity C-reactive protein (hs-CRP) 8 mg / L or ESR 28mm / H -DAS28ESR>5.1. In one embodiment, the subject whose rheumatoid arthritis treatment has failed to respond to at least one DMARD other than the antibody is a subject whose rheumatoid arthritis treatment has failed to respond to prior DMARD therapy. In various embodiments, the DMARD is selected from the group consisting of methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. In various embodiments, the DMARD is methotrexate. In another embodiment, the subject whose rheumatoid arthritis treatment has failed prior administration of one or more DMARDs other than the antibody is a subject who has had an inappropriate response or intolerance to methotrexate. According to the present invention, for individuals whose rheumatoid arthritis has not responded to prior treatment with one or more DMARDs other than the antibody, the antibody is administered to the individual as a monotherapy, instead of the one or more DMARDs. In various embodiments, a subject is intolerant to a DMARD due to one or more physical reactions, conditions, or symptoms caused by treatment with the DMARD. These physical reactions, conditions, or symptoms may include allergies, pain, nausea, diarrhea, azotemia, gastric bleeding, intestinal bleeding, mouth sores, low platelets, intestinal perforation, bacterial infection, inflammation of the mouth or gums, inflammation of the gastric or intestinal mucosa, bacterial sepsis, gastric ulcers, intestinal ulcers, photosensitive skin, dizziness, loss of appetite, low energy, and vomiting. In certain embodiments, intolerance can be determined by the subject or by a medical professional after examining the subject. In various embodiments, the DMARD is selected from the group consisting of methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. In certain embodiments, the DMARD is methotrexate. In other embodiments, the individual suffers from decreased quality of life due to RA. In certain embodiments, the individual suffering from decreased quality of life due to RA scores worse than the mean on a metric selected from the following: change from baseline in the European Quality of Life Five Dimensions Level 3 (EQ-5D-3L), change from baseline in the Rheumatoid Arthritis Disease Impact Index (RAID), work days lost due to arthritis, and decreased work productivity due to arthritis. 50%, arthritis interference with work productivity, days lost from home work due to arthritis, reduced productivity in housework due to arthritis 50% of days, days missed from home / social / leisure activities due to arthritis, days with outside help due to arthritis, rate of RA interference with housework and work productivity, morning stiffness VAS, individual ACR facets - TJC and SJC, individual ACR facets - clinician global VAS, participant global VAS and pain VAS, and individual ACR facets - ESR level. In other embodiments, the subject has a score that is worse than the average HAQ-DI or DAS-28 score before starting treatment. In certain embodiments, an individual with a score that is more severe than average on one or more metrics has a score that is more severe than a baseline value for a metric listed in one or more of Tables 2, 3, 5, or 8 below. In various embodiments, after receiving treatment, an individual with a baseline value or a score that is more severe than a baseline value for a metric listed in one or more of Tables 2, 3, 5, or 8 below indicates that the individual is a poor responder to treatment. In other embodiments, after receiving treatment, an individual with a score that is more severe than a baseline value for a metric listed in one or more of Tables 2, 3, 5, or 8 below indicates that the individual is a poor responder to treatment. In certain embodiments, an individual having a metric score that is more severe than a baseline value for a metric listed in one or more of Tables 2, 3, 5, or 8 has a score that is at least 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100% more severe than baseline. All published materials mentioned herein are incorporated herein by reference in their entirety for all purposes. Example: Randomized, double-blind, parallel-group study evaluating the efficacy and safety of sarukumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis (Study No.: EFC14092, Study Name: SARIL-RA-MONARCH) Target: Main objectives: Sarulumab monotherapy demonstrated superiority to adalimumab monotherapy in terms of signs and symptoms at week 24 in patients with active RA who were intolerant to or considered poor candidates for continuous methotrexate therapy; or who were considered inadequate responders after at least 12 weeks of continuous MTX treatment. Secondary Objectives: In patients with active RA who are intolerant to or considered poor candidates for continuous MTX therapy, or who are considered inadequate responders after at least 12 weeks of continuous MTX treatment, sarulumab monotherapy was shown to be superior to adalimumab monotherapy in: - Reduction in signs and symptoms of RA at week 24 - Improvement in quality of life at Week 24 as measured by a patient-described outcomes questionnaire To assess the safety and tolerability (including immunogenicity) of sarizumab monotherapy throughout the study. [Methodology:] This randomized, double-blind, double-dummy, parallel-group study lasted 24 weeks, followed by open-label sarulumab treatment. Randomization was stratified by region. Number of patients: Planned: 340 Randomization: 369 Treatment received: 368 Evaluated: Effectiveness: 369 Security: 368 Diagnosis and inclusion criteria: Active RA Patients who are intolerant to or considered unsuitable candidates for continuous MTX therapy for 3 months; or who are considered inadequate responders after at least 12 weeks of continuous MTX treatment. Study Treatment Study pharmaceutical products: sarulucab 200 mg q2w or placebo and adalimumab 40 mg q2w or placebo in pre-filled syringes for subcutaneous administration. Duration of treatment: Randomized treatment for 24 weeks Observation duration: Up to 34 weeks during the randomization period (4 weeks screening, 24 weeks treatment, and 6 weeks post-treatment observation if patients do not enter the open-label extension period) Evaluation Criteria Effectiveness: Main evaluation indicators: Change from Baseline in DAS28-ESR at Week 24 Secondary evaluation indicators: DAS28-ESR (remission) - Week 24 ACR50 response - Week 24 ACR70 response - Week 24 ACR20 response - Week 24 HAQ-DI-Week 24 SF-36 Body - Week 24 FACIT Fatigue - Week 24 SF-36 Psychology - Week 24 Security: Adverse events described by patients or noted by the investigators, adjudicated cardiovascular events, and standard hematology and blood chemistry, electrocardiogram (ECG), physical examination, and the presence of anti-drug antibodies to sarcoma. Statistical methods: The efficacy analysis population was the intent-to-treat (ITT) population, which included all randomized subjects. For efficacy analyses, subjects were analyzed in the randomized treatment group, regardless of the treatment they actually received. The primary safety analysis was conducted on all randomized patients exposed to at least one injection of study drug. Subjects in the treatment group they actually received were analyzed, regardless of the randomized group. For the primary efficacy outcome, the change from baseline in the DAS28-ESR at Week 24, data were collected at or before Week 24, including the use of escalating adalimumab (or matching placebo) doses. Data collected after treatment discontinuation were considered missing. No imputation was performed. The primary efficacy measure was assessed using a mixed model for repeated measures (MMRM) with baseline covariates and analysis for treatment, region, visit, and visit-by-treatment interactions. The safety summary is descriptive and does not involve hypothesis testing. The summary of treatment-emergent adverse events (TEAEs) is based on word-by-word MedDRA codes as described by the investigator. A TEAE is defined as any adverse event that develops, worsens, or becomes severe on or after the first dose of the investigational medicinal product (IMP) until the end of the study or the start of extended treatment. The incidence of potentially clinically significant abnormal (PCSA) values ​​is summarized for selected laboratory tests, vital signs, and electrocardiograms. Group characteristics: Three hundred sixty-nine (369) patients represented the ITT population. Three hundred sixty-eight (368) patients represented the safety population. It was determined that 321 (87%) patients successfully completed the 24-week treatment period, of whom 320 continued in the open-label extension phase to continue long-term treatment with sarukinumab. Forty-seven (12.7%) patients permanently discontinued double-blind study treatment, of whom 17 remained with follow-up through Week 24. Demographic and disease characteristics at baseline were generally similar between treatment groups (see Table 2 for baseline values). Compared with adalimumab, patients on sarukinumab tended to be younger, have longer duration of RA, and have lower baseline CRP. The mean duration of study treatment was 158 days in the sarulucab group and 154 days in the adalimumab group. The percentages for patients with 80% were 99% and 100%, respectively. Effectiveness Results: Main evaluation indicators The change from baseline to week 24 in the DAS28-ESR (Disease Activity Score 28-Erythrocyte Sedimentation Rate) score showed a significantly greater reduction in the sarulucab group compared with the adalimumab group (mean difference 1.077 units, p-value < 0.0001, Table 3). This effect was seen as early as week 12. Planned sensitivity analyses confirmed these data. Secondary evaluation indicators Table 4 shows the prespecified strata for the primary and secondary efficacy measures, including assessments of quality of life / physical function. Results in boldface are statistically significant according to the analysis procedures. The least statistically significant measure across the tested strata was the SF-36 Physical score. a values ​​represent the number and percentage of responders for bivariate variables and the LS mean and standard error of the change from baseline for continuous variables. bNominal p-values. All values ​​in bold are significant according to the hierarchical testing procedure. As shown in Table 4, the number of patients who achieved DAS28-ESR remission (<2.6) at week 24 was significantly higher in the sarulucab group than in the adalimumab group (26.6% of patients vs. 7% of patients, p-value <0.0001). In addition, the data obtained showed that a higher number of patients in the sarulikumab group achieved low disease activity (DAS28-ESR < 3.2) at week 24 compared with the adalimumab group (42.9% of patients in the sarulikumab group vs. 14.1% of patients in the adalimumab group, p-value < 0.0001). In addition, it can be seen from Table 4 that: A higher number of patients in the sarulucab group achieved an ACR20 response at week 24 compared with the adalimumab group (71.7% of patients in the sarulucab group vs. 58.4% of patients in the adalimumab group, p-value < 0.008). A higher number of patients in the sarukinumab group achieved an ACR50 response at week 24 compared with the adalimumab group (45.7% of patients in the sarukinumab group vs. 29.7% of patients in the adalimumab group, p-value < 0.002). A higher number of patients in the sarulucab group achieved an ACR70 response at week 24 compared with the adalimumab group (23.4% of patients in the sarulucab group vs. 11.9% of patients in the adalimumab group, p-value < 0.004). Considering the physical function assessment (HAQ-DI score), a more detailed analysis is provided in Tables 5, 6, and 7. Tables 4 and 5 show that the LS mean change from baseline in HAQ-DI was 0.61 in the sarulucab group and 0.43 in the adalimumab group (p-value < 0.004). LS, least squares; SD, standard deviation; SE, standard error; CI, confidence interval. Table 6 Table 7 shows that the change from baseline in HAQ-DI in the salidomide group was The number of patients with 0.3 was higher (62% of patients in the sarukinumab group vs. 47.6% of patients in the adalimumab group, p-value < 0.006). Table 7 shows that the HAQ-DI in the salidomide group achieved a change from baseline of The number of patients with 0.22 was higher (67.4% of patients in the sarukinumab group vs. 54.1% of patients in the adalimumab group, p-value < 0.006). In addition, Table 8 shows that the change in DAS28-CRP (Disease Activity Score 28-C Reactive Protein) score from baseline to week 24 showed a more significant reduction compared with adalimumab (mean difference of -0.884 units, p-value <0.0001). Compared with adalimumab, a higher number of patients in the sarulikumab group achieved DAS28-CRP remission (<2.6) at week 24 (34.2% of patients in the sarulikumab group vs. 13.5% of patients in the adalimumab group, p-value <0.0001). Table 9 shows that patients in the sarulumab group were also twice as likely to achieve clinical disease activity index (CDAI) remission at week 24 compared to those in the adalimumab group. 2.8). The CDAI is a composite index constructed to measure clinical remission in RA that does not include laboratory tests and is the sum of the values ​​of four facets: SJC (28 joints), number of tender joints (28 joints), patient-wide disease activity (in cm), and clinician-wide assessment (in cm). Scores can range from 0 to 76. See Aletaha, D and Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): A review of their usefulness and validity in rheumatoid arthritis, Clin Exp Rheumatol 2005; 23(Suppl.39): S100-S108, incorporated herein by reference in its entirety. In addition, Table 10 shows that compared with adalimumab, the change in CDAI score from baseline to week 24 was significantly greater in the sarizumab group (mean difference was -3.741 units, p-value < 0.002). EQ-5D-3L: Analysis Group Description ITT population: Number of participants analyzed = participants with EQ-5D-3L scores assessed at baseline and week 24. Here, "n" represents the number of participants with available data in a particular category. Measurements RAID: Analysis Group Description ITT population: Number of participants analyzed = participants with RAID assessments at baseline and Week 24. Measurements WPS-RA: Workdays Lost Due to Arthritis Analysis Group Description ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-RA: Reduced work productivity due to arthritis 50% of the days Analysis Group Description ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-RA: Ratio of arthritis to work productivity interference Analysis Group Description ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-RA: Days lost working from home due to arthritis Description of analysis group ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-RA: Reduced productivity in domestic work due to arthritis 50% of the days Analysis Group Description ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-RS: Number of days missed from family / social / leisure activities due to arthritis Description of analysis group ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-SA: Number of days requiring outside help due to arthritis Analysis Group Description ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements WPS-RS4: Ratio of RA to household work productivity Analysis Group Description ITT population: Number of participants analyzed = participants with a WPS-RA: Individual Item Assessment at baseline and Week 24. Measurements Morning stiffness VAS: Analysis Group Description ITT population: Number of participants analyzed = participants with morning stiffness VAS assessment at baseline and week 24. Measurements Individual ACR facets - TJC and SJC: Analysis Group Description ITT population: Number of participants analyzed = participants with TJC and SJC assessments at baseline and Week 24. Measurements Individual ACR facets: clinician overall VAS, participant overall VAS, and pain VAS Description of analysis group Number of participants analyzed = number of participants with ACR assessments for individual domains at baseline and at designated time points. Here, "n" represents the number of participants with available data for a particular domain. Measurements Individual ACR facet CRP Description of analysis group ITT population. Number of participants analyzed = participants with CRP assessments at baseline and week 24. Measurements Individual ACR facets -ESR: Description of analysis group ITT population. Number of participants analyzed = participants with ESR assessments at baseline and Week 24. Measurements

Claims

1. The use of an antibody in the preparation of a medicament for improving the physical function of an individual with rheumatoid arthritis (RA), wherein: - This antibody specifically binds to the human IL-6 receptor and contains three heavy chain complementarity-determining regions (HCDRs) and three light chain complementarity-determining regions (LCDRs), wherein the three HCDRs are HCDR1, HCDR2, and HCDR3, and the three LCDRs are LCDR1, LCDR2, and LCDR3. HCDR1 contains the amino acid sequence of SEQ ID NO: 3, HCDR2 contains the amino acid sequence of SEQ ID NO: 4, HCDR3 contains the amino acid sequence of SEQ ID NO: 5, LCDR1 contains the amino acid sequence of SEQ ID NO: 6, LCDR2 contains the amino acid sequence of SEQ ID NO: 7, and LCDR3 contains the amino acid sequence of SEQ ID NO:

8. - The antibody is formulated and administered subcutaneously to the individual at a dose of 150 mg or 200 mg every two weeks. - During the administration of this antibody, the individual was not given any other disease-modifying antirheumatic drugs (DMARDs). The individual had previously been unresponsive to at least one DMARD other than the antibody for rheumatoid arthritis, and - the improvement in physical function was characterized by a reduction in the Health Assessment Questionnaire Disability Index (HAQ-DI) score relative to baseline (BL), wherein the individual achieved a reduction of at least 0.22 in BL in the HAQ-DI after at least 24 weeks of administration of the antibody.

2. As requested in claim 1, wherein the individual achieves a reduction of at least 0.30 in BL in HAQ-DI after at least 24 weeks of administration of the antibody.

3. The use of an antibody in the preparation of a medicament to improve the health-related quality of life of individuals with rheumatoid arthritis, wherein: - This antibody specifically binds to the human IL-6 receptor and contains three heavy chain complementarity-determining regions (HCDRs) and three light chain complementarity-determining regions (LCDRs), wherein the three HCDRs are HCDR1, HCDR2, and HCDR3, and the three LCDRs are LCDR1, LCDR2, and LCDR3. HCDR1 contains the amino acid sequence of SEQ ID NO: 3, HCDR2 contains the amino acid sequence of SEQ ID NO: 4, HCDR3 contains the amino acid sequence of SEQ ID NO: 5, LCDR1 contains the amino acid sequence of SEQ ID NO: 6, LCDR2 contains the amino acid sequence of SEQ ID NO: 7, and LCDR3 contains the amino acid sequence of SEQ ID NO:

8. - The antibody is formulated and administered subcutaneously to the individual at a dose of 150 mg or 200 mg every two weeks. - During the administration of this antibody, the individual was not given any other disease-modifying antirheumatic drugs (DMARDs). The individual had previously been unresponsive to at least one DMARD other than the antibody in the treatment of rheumatoid arthritis, and the improvement in health-related quality of life was characterized by an increase in the Short Form-36 Body Surface Scale (SF-36 PCS) relative to baseline (BL), wherein the individual achieved a reduction of at least 2.5 in BL in the SF-36 PCS after at least 24 weeks of administration of the antibody.

4. As requested in claim 3, wherein the individual achieves an increase of at least 3 in BL in SF-36 PCS at least 24 weeks after administration of the antibody.

5. As requested in item 1, wherein prior to administration of the antibody, the individual suffered from a reduced quality of life due to RA.

6. As requested in item 5, wherein the individual’s reduced quality of life due to RA is characterized by a score that is more severe than the average of the following metric units: change in the European Five Dimensions of Quality of Life Level 3 (EQ-5D-3L) relative to baseline, change in the Rheumatoid Arthritis Disease Impact Index (RAID) relative to baseline, number of workdays missed due to arthritis, number of days with a ≥ 50% reduction in work productivity due to arthritis, percentage of work productivity affected by arthritis, number of workdays missed due to arthritis, number of days with a ≥ 50% reduction in housework productivity due to arthritis, number of days missed due to arthritis in family / social / leisure activities, number of days requiring external help due to arthritis, percentage of housework productivity affected by RA, morning tonic VAS, individual ACR components – TJC and SJC, individual ACR components – clinician overall VAS, participant overall VAS and pain VAS, and individual ACR component – ​​ESR content.

7. As requested in claim 1, wherein the individual achieves a reduction of at least 0.60 in BL in HAQ-DI after at least 24 weeks of administration of the antibody.

8. As requested in claim 3, wherein the individual achieves an increase of at least 8 in BL in SF-36 PCS at least 24 weeks after administration of the antibody.

9. For any of the uses in claims 1 to 8, wherein the system previously administered at least one DMARD different from the antibody to an individual who has failed treatment for rheumatoid arthritis has previously failed treatment for rheumatoid arthritis with methotrexate.

10. For any of the uses of claims 1 to 8, wherein the individual with rheumatoid arthritis is an individual with moderate to severe active rheumatoid arthritis.

11. The use of any one of claims 1 to 8, wherein the antibody comprises a heavy chain variable region containing the amino acid sequence of SEQ ID NO: 1 and a light chain variable region containing the amino acid sequence of SEQ ID NO:

2.

12. The use of any one of claims 1 to 8, wherein the antibody comprises a heavy chain containing the amino acid sequence of SEQ ID NO: 9 and a light chain containing the amino acid sequence of SEQ ID NO:

10.

13. The use of any of the claims 1 to 8, wherein the anti-system is sarilumab.

14. For any of the uses described in claims 1 to 8, wherein the anti-antibody system is prepared and administered subcutaneously to an individual at a dose of 150 mg every two weeks.

15. For any of the uses described in claims 1 to 8, wherein the anti-antibody system is prepared and administered subcutaneously to an individual at a dose of 200 mg every two weeks.

16. The use of any of claims 1 to 8, wherein the antibody is administered by a syringe or an auto-injector, or wherein the antibody system is administered by a pH 6.0 buffered aqueous solution containing 21 mM histidine, 45 mM arginine, 0.2% (w / v) polysorbate 20, and 5% (w / v) sucrose.

17. As requested in claim 16, wherein the syringe is formulated as a pre-filled syringe.

18. The use of any of claims 1 to 8, wherein the antibody system is prepared as a buffered aqueous solution and administered, the solution containing at least 130 mg / mL of the antibody.

19. As claimed in claim 18, wherein the buffer solution contains 131.6 mg / mL of the antibody.

20. As claimed in claim 18, wherein the buffer solution contains 175 mg / mL of the antibody.

21. The use of any of claims 1 to 8, wherein the anti-system is a human or recombinant human antibody.