Background Sirukumab, a selective, high-affinity human monoclonal antibody to the interleukin-6 (IL-6) cytokine, is under development for rheumatoid arthritis (RA) and other diseases.
Objectives To evaluate long-term efficacy and safety of sirukumab in patients (pts) with RA refractory or intolerant to anti-tumor necrosis factor (TNF) agents.
Methods This phase 3 study included pts ≥18 years with moderate to severe active RA, and a lack of benefit to ≥1 anti-TNF or intolerance to ≥2 anti-TNFs. Eligible pts were initially randomized 1:1:1 to sirukumab subcutaneous (SC) 50mg q4w, sirukumab SC 100mg q2w, or placebo SC q2w for 24 wks. Placebo-treated pts with <20% improvement in tender and swollen joints at Wk 18 (early escape [EE]) and those remaining on placebo at Wk 24 (crossover) were re-randomized to sirukumab through Wk 52. Efficacy endpoints included ACR response, HAQ-DI scores, DAS28 (CRP) remission rates, and SF-36 scores. Results are presented for these key endpoints at Week 52.
Results 878 pts were initially randomized to placebo (n=294), sirukumab 50 mg q4w (n=292), or sirukumab 100 mg q2w (n=292). Of placebo-treated pts, 94 met EE criteria at Wk 18 and 158 crossed over at Wk 24 and were re-randomized to sirukumab. 60% of pts had received ≥2 prior biologics, including non-TNF–targeted biologics. RA signs and symptoms and patient-reported outcomes (PROs [SF-36 scores]) improved significantly with sirukumab versus placebo through Wk 24. Improvements were maintained through Wk 52 with no dose response (Table 1). Through Wk 52 in the combined sirukumab 50mg q4w and 100mg q2w groups, respectively, an adverse event (AE) was reported for 79.6% and 81.3% of pts and a serious AE was reported for 14.2% and 13.2% of pts; injection-site reactions and alanine aminotransferase increases were the most commonly reported AEs.
Conclusions In this population intolerant or refractory to anti-TNFs/other biologics, sirukumab SC 50mg q4w and 100mg q2w were well tolerated and reduced signs and symptoms of RA and improved PROs through 52 wks of treatment, also among pts who switched from placebo to sirukumab.
Disclosure of Interest Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, and Eisai, Speakers bureau: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, and GlaxoSmithKline, D. Aletaha Grant/research support from: AbbVie, Pfizer, Grünenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, Consultant for: AbbVie, Pfizer, Grünenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, P. Agarwal Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, R. Kurrasch Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, P. Tak Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, S. Popik Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC