Background Sirukumab, a human monoclonal antibody that selectively binds to the IL-6 cytokine with high affinity, is under development for rheumatoid arthritis (RA) and other diseases.
Objectives To evaluate efficacy and safety of sirukumab in patients (pts) with RA refractory to conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs).
Methods In this Phase 3 global study, 1,670 pts with active RA and inadequate response to DMARDs were randomized (1:1:1) to sirukumab subcutaneous (SC) 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Pts on placebo with insufficient improvement (<20%) at Wks 18 or 40 or still on placebo at Wk 52 were re-randomized to receive blinded treatment in 1 of the 2 sirukumab doses. Co-primary endpoints were the proportion of pts achieving ACR20 at Wk 16 and change from baseline in modified van der Heijde/Sharp (vdH-S) radiographic damage mean score at Wk 52.
Results For both co-primary endpoints, sirukumab 50mg q4w and 100mg q2w showed significant improvement vs placebo (Table; all P<0.001). All major secondary endpoints were met for both sirukumab doses. Significantly greater improvements were also observed in both the physical and mental component summary scores of the Short Form-36 (SF-36) Health Survey with both sirukumab doses vs placebo at Wk 52 (all P<0.001). Significantly more pts on sirukumab did not experience radiographic progression from baseline to Wk 52 (50mg q4w, 59.0%; 100mg q2w, 62.4%) than on placebo (45.5%; both P<0.001). Through Wk 52, incidences of treatment-emergent adverse events (AEs) and serious AEs, respectively, were numerically higher with sirukumab 50mg q4w (79.6% and 11.0%) and 100mg q2w (80.2% and 9.8%) vs placebo (65.5% and 6.8%). The most common AEs (≥8%) with sirukumab were elevated liver enzymes, upper respiratory tract infection, and injection site erythema, and nasopharyngitis.
Conclusions In DMARD-inadequate responders, sirukumab SC 50mg q4w and 100mg q2w reduced signs/symptoms of RA, inhibited radiographic progression, and improved health-related quality of life. The safety profile of sirukumab was consistent with the known safety profile of anti-IL-6 treatment.
Disclosure of Interest T. Takeuchi Grant/research support from: Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co., Ltd., Celtrion, Nipponkayaku Co. Ltd, C. Thorne Grant/research support from: Abbvie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: Abbvie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, R. Rao Shareholder of: GSK, Employee of: GSK, K. Fei Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC