Title: 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

Authors: Aletaha D., Bingham C.O., Tanaka Y., Agarwal P., Kurrasch R., Tak P.P., Popik S. (2017) The Lancet


What You Need to Know:

Compared with placebo, sirukumab significantly improved the signs and symptoms of active rheumatoid arthritis and was well tolerated in patients who were refractory or intolerant to anti-TNF agents and other biologics, a difficult-to-treat population.

Trial Design:

  • Randomized, double-blind, placebo-controlled, parallel-group, multicenter study
  • Active rheumatoid arthritis patients, 18 years of age or older, with four or more of 68 tender joints and four or more of 66 swollen joints, and refractory or intolerant to previous treatment with at least one anti-TNF drug
  • Patients assigned randomly (1:1:1) to either placebo every 2 weeks, sirukumab 50mg every 4 weeks, or sirukumab 100mg every 2 weeks, all given for 52 weeks or less
  • Patients continued using concomitant disease-modifying antirheumatic drugs (DMARDs)
  • At week 18, placebo-treated patients meeting early escape criteria (<20% improvement in swollen and tender joint counts) were randomly reassigned to either sirukumab 50mg or 100mg
  • Remaining placebo-treated patients were subsequently randomly reassigned at week 24 to either sirukumab dose (crossover)
  • Primary outcome was proportion of patients who achieved a response of at least 20% improvement at week 16 according to American College of Rheumatology criteria (ACR20) in the intention-to-treat population
  • Safety analyses included all participants who received at least one dose (partial or complete) of study drug

Key Outcomes:

  • 878 patients randomly assigned: placebo (n=294), sirukumab 50mg every 4 weeks (n=292), and sirukumab 100mg every 2 weeks (n=292)
  • 523 (60%) had previously received two or more biological treatments including non-TNF drugs; 166 (19%) were not taking a DMARD at baseline
  • At week 16, proportions of patients who achieved an ACR20 response were: 40% for sirukumab 50mg every 4 weeks, 45% for sirukumab 100mg every 2 weeks and 24% for placebo
  • Differences compared with placebo: 0.16 (95% CI 0.09–0.23) for sirukumab 50mg and 0.21 (0.14–0.29) for sirukumab 100mg (both p<0.0001)
  • Adverse events similar across groups
  • Most common adverse events: injection-site erythema