A Randomized, Double-Blind, Placebo-Controlled Phase III Trial On The Efficacy and Safety of Tocilizumab in Patients With Colchicine-Resistant or -Intolerant Familial Mediterranean Fever

Abstract

Objective To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in patients with familial Mediterranean fever (FMF). Methods We performed a double-blind, randomized, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study. Results We randomly assigned 23 patients to either TCZ (n = 11) or placebo (n = 12). The TCZ–placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189–2.531; P = 0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240–0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. Conclusion Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

Interleukin-6 inhibition in the treatment of autoinflammatory diseases

“…A placebo-controlled randomized controlled trial was conducted to evaluate the efficacy and safety of TCZ in Japanese FMF patients unresponsive or intolerant to colchicine. While the primary goal of reduction in the number of fever attacks was not achieved, TCZ was found to effectively reduce febrile attacks and other FMF symptoms and showed stable outcomes after long-term treatment ( 48 ).…”