Sirukumab was more effective than placebo in patients with rheumatoid arthritis (RA) for whom therapy with at least one anti-tumor necrosis factor (TNF) inhibitor failed, according to results from the phase 3 SIRROUND- T study published in The Lancet. Sirukumab is the first monoclonal antibody to target the interleukin-6 cytokine.
In an interview with Rheumatology Advisor, lead investigator Daniel Aletaha, MD, consultant physician and associate professor at the Medical University of Austria, explained that there is a need for novel agents in RA despite numerous current and emerging treatment options. “Now that ‘treat-to-target’ is an established strategy in the management of RA, any new option offers potential benefit to patients — particularly if new options, as shown in the present study, provide evidence of efficacy in patients who have failed other compounds and particularly other biologicals.” The “treat-to-target” approach involves the use of validated composite measures of disease activity to guide the adjustment of therapies until a pre-established treatment target of remission or low disease activity is met.Patients who qualified for SIRROUND-T were an “exceptionally treatment-resistant population,” according to the research team.
High-Yield Data Summary
- Treatment with subcutaneous sirukumab (50 mg/4 weeks and 100 mg/2 weeks) was associated with improvements in symptoms, physical function, and health status in highly refractory and difficult-to-treat RA.
In addition to having active RA, all participants had previously been treated with TNF-inhibitor therapy and either failed to benefit from one or more anti-TNF agents, were intolerant to 2 or more anti-TNF agents, or had documented intolerance to an anti-TNF agent precluding further use of other drugs in the same class. Of the 878 study participants, 523 (60%) had previously been treated with 2 or more biological therapies, including non-TNF agents.
The study met its primary end point of the proportion of patients with a minimum 20% improvement in American College of Rheumatology response criteria (ACR20) at week 16. Results showed that at week 16, ACR20 response was achieved in 40% of patients (117 of 292) who received 50 mg subcutaneous sirukumab every 4 weeks and 45% of patients (132 of 292) who received 100 mg sirukumab every 2 weeks compared with 24% of patients (71 of 294) who received placebo injections. Compared with placebo, differences were 0.16 (95% CI, 0.09-0.23) for the 50-mg arm and 0.21 (95% CI, 0.14-0.29) for the 100-mg arm (both P <.0001). The rate of adverse events in all treatment arms, most commonly injection-site erythema, was similar for the 24-week placebo-controlled period.
Summary and Clinical Applicability
“In this highly refractory and difficult-to-treat population of patients with rheumatoid arthritis, treatment with subcutaneous sirukumab (50 mg every 4 weeks and 100 mg every 2 weeks) was associated with rapid and sustained improvements in signs and symptoms of rheumatoid arthritis, and improvements in physical function and health status,” wrote the investigators.
“These improvements were noted with both dosing regimens, even in patients who had previously not responded to two or more previous biological treatments, as well as in patients who had previously received tocilizumab.”
- Results may not be applicable to the wider population of patients with RA due to the severity of disease and requirement for previous treatment failure with biological therapy in the study cohort.
- Treatment responses may have been lower due to the selection of a difficult-to-treat population.
- Indirect comparisons between this study and other studies’ results could be restricted due to differences in regional enrollment and the specific population selected.
- Only 2 doses and dosing intervals were evaluated.
Dr Aletaha has served as a consultant for or received grant or research support from AbbVie, Pfizer, Grünenthal, Merck Medac, UCB, Mitsubishi-Tanabe, Janssen, and Roche. Dr Bingham has served as a consultant for or received grant support from AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Regeneron, Sanofi, and UCB. Dr Tanaka has received speaking fees from AbbVie, Chugai, Daiichi-Sankyo, Bristol-Myers Squibb, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, and GlaxoSmithKline and has received research grants from Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers Squibb, MSD, Astellas, AbbVie, and Eisai. Drs Agarwal and Popik are employees and shareholders of Janssen Research & Development, LLC. Drs Kurrasch and Tak are employees and shareholders of GlaxoSmithKline.
Aletaha D, Bingham CO, Tanaka Y, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study [published online February 15, 2017]. Lancet. doi:10.1016/S0140-6736(17)30401-4