METHOD OF DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS
The present disclosure relates to the use of an anti-IL6 receptor antibody for treating rheumatoid arthritis in subjects with serum concentrations of certain biomarkers.
1 - 87 . (canceled)
88 . A method of treating rheumatoid arthritis comprising:
administering, to a subject with rheumatoid arthritis whose serum sample is determined to have a pre-dose (baseline) serum concentration of hepcidin greater than 17 ng/mL, an anti-interleukin 6 receptor (anti-IL-6R) antibody,
wherein the anti-IL-6R antibody specifically binds human interleukin-6 receptor (IL-6R) and comprises three heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:1, and three light chain CDRs (LCDRs) of a light chain variable region comprising the amino acid sequence of SEQ ID NO:2.
89 . The method of claim 88 , wherein the HCDRs comprise HCDR1, HCDR2, and HCDR3, and the LCDRs comprise LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 7, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.
90 . The method of claim 88 , wherein the anti-IL-6R antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2.
91 . The method of claim 88 , wherein the anti-IL-6R antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.
92 . The method of claim 88 , wherein the anti-IL-6R antibody is sarilumab.
93 . The method of claim 88 , wherein the subject achieves, after at least 24 weeks of treatment with the anti-IL-6R antibody:
(a) an American College of Rheumatology 20% (ACR20); and/or
(b) an improvement in at least one Patient-Reported Outcome selected from: Patient Global Visual Analogue Scale (VAS) score, Pain VAS score, morning stiffness VAS score, and Rheumatoid Arthritis Impact of Disease (RAID) score.
94 . The method of claim 88 , wherein the subject (i) has moderate to severe rheumatoid arthritis, and/or (ii) has had an inadequate response or is intolerant to one or more disease-modifying antirheumatic drugs (DMARDs) other than the anti-IL-6R antibody.
95 . The method of claim 94 , wherein the subject has had an inadequate response or is intolerant to one or more disease-modifying antirheumatic drugs (DMARDs) comprising methotrexate.
96 . The method of claim 88 , wherein the pre-dose (baseline) serum concentration of hepcidin is greater than 28.9 ng/ml.
97 . The method of claim 88 , wherein the pre-dose (baseline) serum concentration of hepcidin is greater than 43.9 ng/ml.
98 . The method of claim 88 , wherein the anti-IL-6R antibody is administered to the subject subcutaneously at a dose of about 150 mg once every two weeks.
99 . The method of claim 88 , wherein the anti-IL-6R antibody is administered to the subject subcutaneously at a dose of about 200 mg once every two weeks.
100 . A method of selecting a subject with rheumatoid arthritis (RA) who has an increased propensity for effective treatment with an anti-interleukin 6 receptor (anti-IL-6R) antibody comprising:
measuring a pre-dose (baseline) serum concentration of hepcidin in a serum sample from a subject with RA,
wherein if the serum sample has a pre-dose (baseline) serum concentration of hepcidin greater than 17 ng/mL, the subject is selected as having an increased propensity for effective treatment with an anti-IL-6R antibody,
wherein the anti-IL-6R antibody specifically binds IL-6R and comprises three heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:1, and three light chain CDRs (LCDRs) of a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2.
101 . The method of claim 100 , wherein the HCDRs comprise HCDR1, HCDR2, and HCDR3, and the LCDRs comprise LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 7, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.
102 . The method of claim 100 , wherein the anti-IL-6R antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2.
103 . The method of claim 100 , wherein the anti-IL-6R antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.
104 . The method of claim 100 , wherein the anti-IL-6R antibody is sarilumab.
105 . The method of claim 100 , wherein the pre-dose (baseline) serum concentration of hepcidin is greater than 43.9 ng/ml.
106 . The method of claim 100 , wherein the subject who is selected as having an increased propensity for effective treatment of RA with the anti-IL-6R antibody has an increased propensity of achieving, after at least 24 weeks of treatment with the anti-IL-6R antibody:
(a) an American College of Rheumatology 20% (ACR20); and/or
(b) an improvement in at least one Patient-Reported Outcome selected from: Patient Global Visual Analogue Scale (VAS) score, Pain VAS score, morning stiffness VAS score, and Rheumatoid Arthritis Impact of Disease Score (RAID) score.
107 . The method of claim 100 , further comprising administering to the selected subject the anti-IL-6R antibody subcutaneously a dose of about 150 mg to about 200 mg once every two weeks.