Objectives Interleukin-6 (IL-6) is implicated in rheumatoid arthritis (RA) pathophysiology. Unlike IL-6 receptor inhibitors, sirukumab is a human monoclonal antibody that selectively binds to the IL-6 cytokine. The phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group SIRROUND-D study (ClinicalTrials.gov identifier NCT01604343) evaluated the efficacy and safety of sirukumab in patients with active RA refractory to disease-modifying antirheumatic drugs.
Methods Patients were randomised 1:1:1 to treatment with sirukumab 100 mg every 2 weeks, 50 mg every 4 weeks or placebo every 2 weeks subcutaneously. Results through week 52 are reported.
Results Of 1670 randomised patients, significantly more patients achieved American College of Rheumatology 20% (ACR20) response at week 16 (coprimary endpoint) with sirukumab 100 mg every 2 weeks (53.5%) or 50 mg every 4 weeks (54.8%) versus placebo (26.4%; both p<0.001). Mean (SD) change from baseline in modified Sharp/van der Heijde score at week 52 (coprimary endpoint) was significantly lower with sirukumab (100 mg every 2 weeks: 0.46 (3.26); 50 mg every 4 weeks: 0.50 (2.96)) versus placebo (3.69 (9.25); both p<0.001). All major secondary endpoints (week 24 Health Assessment Questionnaire–Disability Index change from baseline, ACR50 response, 28-joint Disease Activity Score based on C reactive protein and major clinical response (ACR70 for six continuous months by week 52)) were met. The most common adverse events with sirukumab were elevated liver enzymes, upper respiratory tract infection, injection site erythema and nasopharyngitis.
Conclusions Sirukumab 100 mg every 2 weeks and 50 mg every 4 weeks led to significant reductions in RA symptoms, inhibition of structural damage progression and physical function and quality of life improvements, with an expected safety profile.
Trial registration number NCT01604343; Results.
- rheumatoid arthritis
- DMARDs (biologic)
- DMARDs (synthetic)
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Handling editor Tore K Kvien
Contributors TT, CT, GK, SS, WX, RR, BH and PPT contributed to the study design. TT and KF contributed to patient recruitment and treatment. TT, CT, GK, WX, RR, KF and BH contributed to the conduct of the study. SS and KF collected the data. CT, GK, SS, WX, RR, KF, BH and PPT analysed the data. All authors interpreted the data, 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, LLC, in collaboration with GlaxoSmithKline. Writing and editorial support were provided by Allison Michaelis, PhD, of MedErgy, and were funded by Janssen Global Services, LLC and GlaxoSmithKline.
Competing interests TT: 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, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd. and SymBio Pharmaceuticals Ltd; consultant for AstraZeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol-Myers K.K. and Nipponkayaku Co. Ltd.; speakers bureau for AbbVie GK, Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Astellas Pharma, Daiichi Sankyo Co., Ltd., Celtrion and Nipponkayaku Co. Ltd. CT: grant/research support from Celgene, Novartis and Pfizer; advisory board and consultant for AbbVie, Amgen, Celgene, Hospira, Lilly, Novartis and Pfizer; steering committee for Janssen/Centocor/Johnson & Johnson. GK: grant/research support from Pfizer; consultant for Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Pfizer, Regeneron, Roche and Sanofi; speakers bureau for Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Pfizer, Regeneron, Roche and Sanofi. SS, WX, KF and BH: employees and shareholders of Janssen Research & Development, LLC. RR and PPT: employees and shareholders of GlaxoSmithKline.
Provenance and peer review Not commissioned; externally peer reviewed.
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