HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial.

AbstractBACKGROUND:
Currently, 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.
OBJECTIVE:
To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF.
DESIGN:
Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907).
SETTING:
6 U.S. sites.
PATIENTS:
Patients with FMF aged 4 years or older with 1 or more attacks per month.
INTERVENTION:
One 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.
MEASUREMENTS:
Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo.
RESULTS:
8 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.
LIMITATION:
Small sample size, heterogeneity of FMF mutations, age, and participant indication (colchicine resistance or intolerance) were study limitations.
CONCLUSION:
Rilonacept reduces the frequency of FMF attacks and seems to be a treatment option for patients with colchicine-resistant or -intolerant FMF.
PRIMARY FUNDING SOURCE:
U.S. Food and Drug Administration, Office of Orphan Products Development.
AuthorsPhilip 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, Daniel J Lovell
JournalAnnals of internal medicine (Ann Intern Med) Vol. 157 Issue 8 Pg. 533-41 (Oct 16 2012) ISSN: 1539-3704 [Electronic] United States
PMID23070486 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Receptors, Interleukin-1 Type I
  • Recombinant Fusion Proteins
  • rilonacept
  • Colchicine
Topics
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Colchicine (adverse effects, therapeutic use)
  • Double-Blind Method
  • Drug Resistance
  • Familial Mediterranean Fever (drug therapy)
  • Female
  • Humans
  • Male
  • Receptors, Interleukin-1 Type I (therapeutic use)
  • Recombinant Fusion Proteins (adverse effects, therapeutic use)
  • Treatment Outcome
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: