Background Efficacy and safety of sirukumab, a selective, high-affinity human monoclonal antibody to IL-6, have recently been evaluated in a global Phase 3 study in patients (pts) with active rheumatoid arthritis (RA) refractory to conventional disease-modifying anti-rheumatic drugs (DMARDs).
Objectives To compare efficacy and radiographic progression of sirukumab in subgroups of pts with active RA despite DMARD treatment who previously received biologic therapy (biologic-experienced) and who previously only received synthetic DMARDs (biologic-naïve).
Methods Pts were randomized (1:1:1) to sirukumab subcutaneous (SC) 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w. Pts on placebo with insufficient (<20%) improvement at Wks 18 or 40 or still on placebo at Wk 52 were re-randomized to sirukumab treatment (1 of the 2 doses). The co-primary efficacy endpoints were: Wk 16 ACR20 response and Wk 52 change from baseline (BL) in modified vdH-S radiographic score. This post-hoc analysis compared efficacy for biologic-naïve and -experienced pts within biologic experience category for sirukumab vs placebo, and across experience category within sirukumab dose group.
Results Improvements were observed in all outcomes for sirukumab vs placebo, regardless of prior biologic use (all P<0.001 within biologic experience categories; Table). 34.9% (583/1,670) of pts were prior biologic-experienced; efficacy with sirukumab was comparable for pts who had taken 1 or ≥2 prior biologics. At BL, compared with biologic-naïve pts, biologic-experienced pts had longer disease duration (mean, 11 vs 7 yrs; P<0.0001) and worse HAQ-DI scores (mean, 1.58 vs 1.49; P=0.02). No differences between prior biologic-naïve and -experienced pts were observed in either sirukumab dose group for the co-primary endpoints (both P≥0.1) as well as for Wk 24 ACR50 response, DAS28 (CRP) remission, or Wk 52 mean DAS28 change from BL (all P≥0.1).
Conclusions Both sirukumab doses significantly reduced RA signs/symptoms and inhibited radiographic progression vs placebo within prior biologic use categories, with comparable efficacy observed between biologic-naïve and -experienced pts for both sirukumab doses.
Disclosure of Interest 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, 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, S. Sheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, W. Xu Employee of: Janssen Research & Development, LLC, S. Xu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, 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