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  • Title: Incomplete response to colchicine in M694V homozygote FMF patients.
    Author: Lidar M, Yonath H, Shechter N, Sikron F, Sadetzki S, Langevitz P, Livneh A, Pras E.
    Journal: Autoimmun Rev; 2012 Nov; 12(1):72-6. PubMed ID: 22884555.
    Abstract:
    BACKGROUND: Previous studies have shown that with prophylactic colchicine 65% of the patients suffering from Familial Mediterranean fever (FMF) will show a complete response, 30% a partial response and about 5% will show minimum or no response. These studies were performed before the isolation of the disease gene. Genotyping enables us to study the response rates according to specific mutations. We have witnessed a large number of M694V homozygotes who do not respond well to colchicine despite being treated with maximal sustained doses. AIM: To assess the response rates to colchicine in M694V homozygote FMF patients in comparison to other prevalent genotypes. METHODS: We conducted a telephonic survey which included 112 FMF patients: 40 M694V homozygotes, and 2 comparison groups of 41 M694V/V726A compound heterozygotes and 31 V726A homozygotes. The questionnaire included demographic, social and clinical features, colchicine dose, response rates and reported side effects. RESULTS: M694 homozygotes showed a more severe disease, and were treated with higher doses of colchicine (average dose 1.98±0.56 compared to 1.47±0.58, p=0.0001 and 1.13±0.41, p<0.001 in the M694V/V726A compound heterozygotes and the V726A homozygotes, respectively); Colchicine related side effects were noted in 40% of the M694V homozygotes. The average rate of attacks in treated M694V homozygotes (0.70±1.06) was higher compared to the two other groups (0.14±0.26, p=0.002 and 0.08±0.20, p=0.0009, respectively) and only 25% of them reported no attacks in the last year. None of the patients who took part in this study had amyloidosis. Side effects limiting the dose of colchicine were noted in 40% of the M694V homozygotes. CONCLUSIONS: Despite receiving higher doses of colchicine the prevalence of complete responders among M694V homozygotes is much lower than previously appreciated. The results highlight the need for additional treatment modalities for these patients.
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