Long-term safety and efficacy of sirukumab for patients with rheumatoid arthritis who previously received sirukumab in randomised controlled trials (SIRROUND-LTE)

Abstract

Objective: Interleukin (IL)-6 is a pleiotropic cytokine involved in the pathophysiology of rheumatoid arthritis (RA). Sirukumab is a human monoclonal antibody that binds to IL-6 with high affinity and specificity.

Methods: This long-term extension (LTE) study of the SIRROUND-D and SIRROUND-T studies assessed long-term safety and efficacy of sirukumab in adults with moderate-to-severe RA refractory to conventional disease-modifying antirheumatic drug therapy or antitumor necrosis factor agents. Patients received sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) or sirukumab 50 mg SC every 4 weeks (q4w).

Results: 1820 patients enrolled in the LTE; median exposure was 2.34 and 2.07 years in sirukumab 50 mg q4w and 100 mg q2w groups, respectively. Adverse events (AEs) occurred in similar proportions between groups, with the exception of major adverse cardiovascular events (MACE), which were more common in the 50 mg q4w versus 100 mg q2w group (2.2% vs 1.0%), and injection-site reactions, more common in the 100 mg q2w group versus 50 mg q4w group (7.5% vs 3.7%). The most common serious AEs were infections (10% of the patients); 32 (1.8%) patients died during the study (primarily from serious infection and MACE). Malignancies were reported in 24 (1.3%) patients. Gastrointestinal perforations, hepatobiliary abnormalities and changes in laboratory parameters were rare. Reductions in RA signs and symptoms and improvements in physical function were maintained throughout the LTE.

Conclusions: The safety profile of sirukumab in the LTE remained consistent with that reported in SIRROUND-D and SIRROUND-T and efficacy was maintained.

Trial registration number: NCT01856309.

Keywords: antirheumatic agents; arthritis; rheumatoid; therapeutics.

Conflict of interest statement

Competing interests: DA has received consulting and/or speaking fees from AbbVie, Amgen, Celgene, Gilead, Galappagos, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz and Sanofi/Genzyme. COB has received consulting fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Genentech/Roche, Janssen, Pfizer and Regeneron/Sanofi and grant support from Bristol-Myers Squibb and Janssen. CT has received consulting and/or advisory board fees from AbbVie, Amgen, AstraZeneca, BMS, Celgene, CaREBiodam, Centocor, Genzyme, GSK, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Takeda, TcLand and UCB and speaker fees from Medexus/Medac. GAK has received advisory and/or speaking fees from Bristol-Myers Squibb, Sanofi-Genzyme Regeneron and Janssen and grant support from Pfizer. TT has received grants from Astellas, Chugai, Daiichi Sankyo, Takeda, AbbVie GK, Asahi Kasei, Mitsubishi Tanabe, Eisai, Nippon Kayaku and JCR, speaking fees and/or honoraria from AbbVie GK, Chugai, Bristol-Myers KK, Eli Lilly Japan KK, SRL, Astellas, AYUMI, Eisai, Ono, Kissei, Gilead Sciences, Mitsubishi Tanabe, Novartis Pharma KK, Pfizer Japan, Taiho, Daiichi Sankyo, Taisho, Nippon Kayaku, Boehringer Ingelheim, A2 Healthcare and The Uehara Memorial Foundation and consulting fees from Astellas, AbbVie GK, Ono, Gilead Sciences, Taiho, Daiichi Sankyo, Taisho, Nippon Kayaku, Bristol-Myers KK, Chugai, Novartis Pharma KK, A2 Healthcare Corporation and Boehringer Ingelheim. AB was an employee at Janssen when the study was performed and is currently an employee at Merck. PA is an employee of Janssen Pharmaceuticals. BH was an employee at Janssen when the study was performed. RR was an employee at GlaxoSmithKline when the study was performed. KB was an employee at GlaxoSmithKline when the study was performed and is currently an employee at Incyte. YT has received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen and Teijin and research grants from Asahi Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai and Ono.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Disposition of patients enrolling from SIRROUND-D and SIRROUND-T into SIRROUND-LTE. q2w, every 2 weeks; q4w, every 4 weeks.

Figure 2

(A) Proportion of patients with ACR50 response from baseline of primary studies to the end of the SIRROUND-LTE study period. (B) Proportion of patients with DAS28 (CRP) remission from baseline of primary studies to the end of the SIRROUND-LTE study period. (C) Proportion of patients with SDAI-based ACR/EULAR remission from baseline of primary studies to the end of the SIRROUND-LTE study period. (D) Proportion of patients with HAQ-DI response from baseline of primary studies to the end of the SIRROUND-LTE study period. ACR, American College of Rheumatology; BL, baseline; DAS28 (CRP), Disease Activity Index Score 28 (C reactive protein); HAQ-DI, Health Assessment Questionnaire-Disability Index; LTE, long-term extension; q2w, every 2 weeks; q4w, every 4 weeks; SDAI, Simplified Disease Activity Index.