PMID- 24699939 OWN - NLM STAT- MEDLINE DCOM- 20141016 LR - 20220410 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 73 IP - 9 DP - 2014 Sep TI - Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. PG - 1616-25 LID - 10.1136/annrheumdis-2013-205137 [doi] AB - OBJECTIVES: The safety and efficacy of sirukumab, an anti-interleukin-6 (IL-6) monoclonal antibody, were evaluated in a 2-part, placebo-controlled phase II study of patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: In Part A (proof-of-concept), 36 patients were randomised to placebo or sirukumab 100 mg every 2 weeks (q2w) through week 10, with crossover treatment during weeks 12-22. In Part B (dose finding), 151 patients were randomised to sirukumab (100 mg q2w, 100 mg q4w, 50 mg q4w, or 25 mg q4w) through week 24, or placebo through week 10 with crossover to sirukumab 100 mg q2w (weeks 12-24). The proportion of patients with an American College of Rheumatology 50 (ACR50) response and the change from baseline in the 28-joint count disease activity score using C-reactive protein (DAS28-CRP) were determined. Safety was evaluated through week 38 in both parts. RESULTS: The primary endpoint (ACR50 at week 12 in Part B) was achieved only with sirukumab 100 mg q2w versus placebo (26.7% vs 3.3%; p=0.026). Greater improvements in mean DAS28-CRP at week 12 were observed with sirukumab 100 mg q2w versus placebo in Parts A (2.1 vs 0.6, p<0.001) and B (2.2 vs 1.1; p<0.001). The incidence of adverse events (AEs) was similar for sirukumab-treated and placebo-treated patients through week 12 in Part A (70.6% and 63.2%, respectively) and B (67.8% and 66.7%, respectively). Infections were the most common type of AE; one death occurred (Part B, sirukumab 100 mg q2w, brain aneurysm). CONCLUSIONS: Sirukumab-treated patients experienced improvements in the signs/symptoms of RA. Safety results through 38 weeks were consistent with other IL-6 inhibitors. TRIAL REGISTRATION NUMBER: NCT00718718. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - Smolen, Josef S AU - Smolen JS AD - Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria Department of Medicine, Hietzing Hospital, Vienna, Austria. FAU - Weinblatt, Michael E AU - Weinblatt ME AD - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Sheng, Shihong AU - Sheng S AD - Janssen Research & Development, LLC, Quantitative Sciences, Spring House, Pennsylvania, USA. FAU - Zhuang, Yanli AU - Zhuang Y AD - Janssen Research & Development, LLC, Biologics Clinical Pharmacology, Spring House, Pennsylvania, USA. FAU - Hsu, Benjamin AU - Hsu B AD - Janssen Research & Development, LLC, Immunology, Spring House, Pennsylvania, USA. LA - eng SI - ClinicalTrials.gov/NCT00718718 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140403 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Biomarkers) RN - 0 (Interleukin-6) RN - 640443FU93 (sirukumab) RN - 9007-41-4 (C-Reactive Protein) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM CIN - doi: 10.1136/annrheumdis-2013-205002 MH - Adult MH - Aged MH - Antibodies, Monoclonal/administration & dosage/adverse effects/blood/*therapeutic use MH - Antibodies, Monoclonal, Humanized MH - Antirheumatic Agents/administration & dosage/adverse effects/blood/*therapeutic use MH - Arthritis, Rheumatoid/blood/*drug therapy MH - Biomarkers/blood MH - C-Reactive Protein/metabolism MH - Cross-Over Studies MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Humans MH - Interleukin-6/*antagonists & inhibitors MH - Male MH - Methotrexate/therapeutic use MH - Middle Aged MH - Severity of Illness Index MH - Treatment Outcome PMC - PMC4145446 OTO - NOTNLM OT - Cytokines OT - DMARDs (biologic) OT - Methotrexate OT - Rheumatoid Arthritis OT - Treatment EDAT- 2014/04/05 06:00 MHDA- 2014/10/17 06:00 CRDT- 2014/04/05 06:00 PHST- 2014/04/05 06:00 [entrez] PHST- 2014/04/05 06:00 [pubmed] PHST- 2014/10/17 06:00 [medline] AID - annrheumdis-2013-205137 [pii] AID - 10.1136/annrheumdis-2013-205137 [doi] PST - ppublish SO - Ann Rheum Dis. 2014 Sep;73(9):1616-25. doi: 10.1136/annrheumdis-2013-205137. Epub 2014 Apr 3.