• Philip J Hashkes, Steven J Spalding, Edward H Giannini, Bin Huang, Anne Johnson, Grace Park, Karyl S Barron, Michael H Weisman, Noune Pashinian, Andreas O Reiff, Jonathan Samuels, Dowain A Wright, Daniel L Kastner, and Daniel J Lovell.
• Pediatric Rheumatology Unit, Shaare Zedek Medical Center, POB 3235, Jerusalem, 91031 Israel. hashkesp@szmc.org.il
• Ann. Intern. Med. 2012 Oct 16; 157 (8): 533-41.

BackgroundCurrently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF.ObjectiveTo assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF.DesignRandomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907).Setting6 U.S. sites.PatientsPatients with FMF aged 4 years or older with 1 or more attacks per month.InterventionOne of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo.MeasurementsDifferences in the frequency of FMF attacks and adverse events between rilonacept and placebo.Results8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept-placebo attack risk ratio was 0.59 (SD, 0.12) (equal-tail 95% credible interval, 0.39 to 0.85). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, -1.74 [95% CI, -3.4 to -0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [-0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of -4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen in other adverse events.LimitationSmall sample size, heterogeneity of FMF mutations, age, and participant indication (colchicine resistance or intolerance) were study limitations.ConclusionRilonacept reduces the frequency of FMF attacks and seems to be a treatment option for patients with colchicine-resistant or -intolerant FMF.Primary Funding SourceU.S. Food and Drug Administration, Office of Orphan Products Development.

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