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
KeywordsPlacebo Arthritis Primary Outcome Colchicine Primary Outcome Measure
The familial Mediterranean fever 50 score (FMF50) was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.
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.
We reanalyzed the data from the 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.
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.
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 and should be revisited prior to adoption as a primary outcome measure in multinational FMF trials.
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