Objective This randomised, double-blind, parallel-group, phase 3 study compared monotherapy with sirukumab, an anti–interleukin-6 cytokine monoclonal antibody, with adalimumab monotherapy in patients with rheumatoid arthritis (RA).
Methods Biologic-naïve patients with active RA who were inadequate responders or were intolerant to, or inappropriate for, methotrexate were randomised to subcutaneous sirukumab 100 mg every 2 weeks (n=187), sirukumab 50 mg every 4 weeks (n=186) or adalimumab 40 mg every 2 weeks (n=186). Primary endpoints at week 24 were change from baseline in Disease Activity Score in 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) and proportion of patients achieving an American College of Rheumatology (ACR) 50 response; these endpoints were tested in sequential order. This study is registered at EudraCT (number: 2013-001417-32) and ClinicalTrials.gov (number: NCT02019472).
Results Significantly greater improvements from baseline in mean (SD) DAS28 (ESR) were observed at week 24 with sirukumab 100 mg every 2 weeks (−2.96 (1.580)) versus adalimumab 40 mg every 2 weeks (−2.19 (1.437); P<0.001). Sirukumab 50 mg every 4 weeks also showed significantly greater improvement from baseline at week 24 in DAS28 (ESR) (−2.58 (1.524)) compared with adalimumab (P=0.013). The ACR50 response rates with the 100 mg (35.3%) and 50 mg (26.9%) doses of sirukumab were comparable to that with adalimumab (31.7%) at week 24. The safety profile of sirukumab was consistent with that observed with anti–interleukin-6 receptor antibodies. A dose-related effect on the incidence of injection-site reactions was observed with sirukumab.
Conclusion Sirukumab monotherapy showed greater improvements in DAS28 (ESR), but similar ACR50 response rates, versus adalimumab monotherapy.
- rheumatoid arthritis
- DMARDs (biologic)
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PPT and BH contributed equally.
Handling editor Josef S Smolen
Contributors PCT, YZ, RK, RR and PPT contributed to the design of the study and analysis and interpretation of the data. MHS, YJ and SD contributed to the analysis and interpretation of the data. QW contributed to the design and conduct of the study, recruitment and treatment of patients, and collection, analysis and interpretation of the data. BH contributed to the design and conduct of the study and the analysis and interpretation of the data. All authors contributed to drafting the work or revising it critically for important intellectual content, provided final approval of the version published and agreed to be accountable for all aspects of the work.
Funding This study was sponsored by Janssen Research & Development in collaboration with GlaxoSmithKline. PCT was supported in part by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).
Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Competing interests PCT has served as a consultant to AbbVie, Biogen, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sandoz and UCB Pharma, and has received research grant funding from Celgene, GlaxoSmithKline, Janssen and UCB Pharma. MHS has served as a consultant to AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Eli Lilly and UCB Pharma, and as a speaker for AbbVie and Bristol-Myers Squibb. QW, YZ and BH are employees and shareholders of Janssen Research & Development. YJ is a contractor of Janssen Research & Development. RK, SD, RR and PPT are employees and shareholders of GlaxoSmithKline.
Patient consent Obtained.
Ethics approval The study protocol and amendments were reviewed by an Independent Ethics Committee or Institutional Review Board. This study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practices and applicable regulatory requirements.
Provenance and peer review Not commissioned; externally peer reviewed.
Author note Portions of the data in this manuscript have been previously presented as an oral presentation at the 2016 ACR/ARHP Annual Meeting (Taylor PC, Schiff M, Wang Q, Jiang Y, Kurrasch R, Daga S, Rao R, Hsu B, Tak PP. Efficacy and safety of monotherapy with sirukumab, an anti–IL-6 cytokine monoclonal antibody, compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis: results of a global, randomized, double-blind, parallel-group, phase 3 study [abstract]. Arthritis Rheumatol. 2016;68[suppl 10]. Available at: http://acrabstracts.org/abstract/efficacy-and-safety-of-monotherapy-with-sirukumab-an-anti-il-6-cytokine-monoclonal-antibody-compared-with-adalimumab-monotherapy-in-biologic-naive-patients-with-active-rheumatoid-arthritis/. Accessed August 2, 2017).