The familial mediterranean fever (FMF) 50 score: Does it work in a controlled clinical trial? re-analysis of the trial of rilonacept for patients with colchicine-resistant or intolerant FMF

Abstract

Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF. Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine. Methods: We re-analyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants) without worsening of the sixth criterion. Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept. Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study.