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Two doses of sirukumab, compared with placebo, improves the signs and symptoms of patients with active rheumatoid arthritis, researchers report.
Researchers from the SIRROUND-T study report that two doses of sirukumab, compared with placebo, improves the signs and symptoms of patients with active rheumatoid arthritis.
The study appears in the February 15 online issue of The Lancet.
“Results of our phase three study indicate that sirukumab, which is directed against the interleukin-6 cytokine, might be an alternative treatment for rheumatoid arthritis, particularly for the challenging patient population that is refractory to anti-TNF drugs and other biological treatments,” wrote Daniel Aletaha, M.D., from the Medical University Vienna in Austria and colleagues.
This was a randomized, double-blind, placebo-controlled trial conducted with 878 patients with active rheumatoid arthritis. Patients were recruited from 183 sites in 20 different counties between July 25, 2012 and January 12, 2016 and were eligible for the study if they were 18 and over, were refractory or intolerant to at least one anti-TNF drug, had four or more tender joints out of 68, and four or more swollen joints out of 66.
Patients were randomized in a 1:1:1 ratio to receive a placebo every two weeks, 50 mg of sirukumab every four weeks, or 100 mg of sirukumab every two weeks. Patients in each group were given their regimen for approximately 52 weeks or less and were permitted to continue taking concomitant disease-modifying antirheumatic drugs. The primary outcome was the proportion of patients who achieved a 20% improvement according to American College of Rheumatology criteria (ACR20) at 16 weeks.
In both sirukumab groups, a higher proportion of patients achieved an ACR20 response at week 16 compared with placebo: 117 (40%) of 292 with 50 mg sirukumab every 4 weeks and 132 (45%) of 292 with 100 mg sirukumab every 2 weeks compared with 71 (24%) of 294 in the placebo group.
Anti-TNF inhibitors in combination with methotrexate are commonly used to manage rheumatoid arthritis; however, not all patients response well to this therapy. Sirukumab, a human monoclonal antibody that binds to the interleukin-6 cytokine, is a potential new therapy for rheumatoid arthritis patients. It works by blocking the interleukin-6 signaling pathway, which has been shown in prior studies to be involved in the pathogenesis of rheumatoid arthritis.
“Our study (SIRROUND-T) is the first phase 3 trial of sirukumab, an agent targeting the IL-6 cytokine, in patients with rheumatoid arthritis,” wrote Aletaha and colleagues.
Roy Fleischmann, M.D., from the University of Texas Southwestern Medical Center provided a commentary on the findings from the SIRROUND-T study in the February 15 online issue of the Lancet.
“Although studies are difficult to compare, mainly because of differences in inclusion or exclusion criteria and different patient populations, without a true head-to-head study SIRROUND-T is best compared with reports assessing the safety and efficacy of two other inhibitors of the interleukin-6 pathway in this patient population: RADIATE, which assessed tocilizumab, and TARGET, which assessed sarilumab, both monoclonal antibodies binding to the interleukin-6 receptor,” wrote Fleischmann.
He goes on to present a calculation of the potential relative clinical effectiveness for each medication by comparing 8 mg/kg tocilizumab every 4 weeks with 200 mg sarilumab every 2 weeks and 50 mg sirukumab every 4 weeks. The calculations show that differences from placebo would be ACR20: 40%, 27%, and 16%; ACR50: 25%, 23%, and 12%; ACR70: 11%, 9%, and 3%; DAS28 (C-reactive protein) less than 2·6: 28%, 22%, and 11% for tocilizumab, sarilumab, and sirukumab, respectively.
Dr. Fleischmann concludes that the results of the SIRROUND-T study support the use of sirukumab for treating patients with active rheumatoid arthritis who are refractory to TNF inhibitor.
Janssen Research & Development, LLC provided funding for this study, in collaboration with GlaxoSmithKline.
Employees of the funders were involved in the study design, data collection, data analysis, data interpretation, and writing of the report. Additionally, DA has served as a consultant for, or received grant or research support from AbbVie, Pfizer, GruÌnenthal, Merck Medac, UCB, Mitsubishi/ Tanabe, Janssen, and Roche. COB III has served as a consultant for, or received grant support from, AbbVie, Amgen, BMS, Janssen, Eli Lilly, Pfizer, Regeneron, Sanofi , and UCB. YT has received speaking fees from AbbVie, Chugai, Daiichi-Sankyo, Bristol-Myers, 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, MSD, Astellas, AbbVie, and Eisai. PA and SP are employees and shareholders of Janssen Research & Development, LLC. RK and PPT are employees and shareholders of GlaxoSmithKline.
Daniel Aletaha, Clifton O Bingham III, Yoshiya Tanaka, 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,”The Lancet. Published online February 15, 2017. DOI: 10.1016/S0140-6736(17)30401-4.
“Interleukin-6 inhibition for rheumatoid arthritis,”
Published online February 15, 2017. DOI: 10.1016/S0140-6736(17)30405-1