OP0273 ADHERENCE TO COLCHICINE TREATMENT AND COLCHICINE RESISTANCE IN A MULTICENTRIC FMF NATIONAL COHORT

Abstract

Background:Colchicine is the standard treatment for Familiar Mediterranean Fever (FMF), however about 5% of patients experience colchicine resistance. There is no standard definition of colchicine resistance. Recently a panel of experts elaborated a new definition based on a Delphi consensus approach.Objectives:We aim to describe main features of the disease and clinical outcome of a cohort of FMF patients with particular interest on the colchicine resistance and tolerability according to the definitions proposed by the recent consensus.Methods:Since November 2009, 425 Italian pediatric and adult FMF patients (pts) from 13 centers were enrolled in a national longitudinal cohort study, using the international EUROFEVER registry. Demographic, genetic and clinical data, including response to treatment, were analyzed. Supplementary information on health related quality of life and treatment adherence was also collected by a specific questionnaire.Results:Complete information were available in 341 pts (189 M and 152 F, 211 children and 120 adults). The median age at disease onset was 5.0 years (1 m-59 y); the mean diagnostic delay was 8.7 y (range 0-61 y). The median age at enrollment was 12.1 y (range 3 m - 82 y). The MEFV genotype was the following: 103 (30.2%) pts carried biallelic pathogenic variants; 59 (17.3%) one pathogenic variants and one VOUS /LB variant; 27 (7.9%) had biallelic VOUS/LB variants; 97 (28.45%) were heterozygous for pathogenic variants; 30 (8.8%) were heterozygous for VOUS/LB, 25 (7.33%) were genetically negative.Colchicine treatment was used in 280 pts; during treatment, biologic treatment (anti-IL1) in 22 pts. 61 pts received NSAID or steroid on demand.We analyzed the behavior of the pts treated with colchicine according to the statements on colchicine resistance/intolerance defined by Ozen et al (1) (Table 1).Table 1.Adherence62% displayed a total adherence (> 90% of prescription); 10.8% a good adherence (50-89% of prescriptions); 1.9% poor adherence (< 50% of prescriptions); 0.9% no adherenceDose adjustment criteria/ Recommended maximum colchicine doseMean colchicine dose:Pts <5 years: 0.57mg/de (std. dev. 0.18)5-10 year: 0.77mg/die (std. dev. 0.23)10-18 years: 1.1mg/die (std. dev. 0.39)Adults: 1.16 mg/die (std. dev. 0.37)Pts with a dose inferior to the minimum recommended dose5-10 years: 2.5%10-18 years: 15%Adults: 4%Resistance to ColchicineResistance was be defined as persistence of fever attacks, despite optimal treatment. 41.6% pts had a complete disease control32.8% Pts had < 1 episode/month for 3 months25.5% had ≥1 episode/month for 3 monthsInclusion of secondary amyloidosis in the definition of colchicine resistance5 adult pts (1.5%) displayed amyloidosisColchicine intolerance11 pts (3.2%) withdraw colchicine because of drug intolerancePatient quality of life and patient-reported outcomes20.7% of pts experience fatigue or chronic pain, 16.9% limitations in daily activities, and 16.9% have lost school/work days.Conclusion:Almost 58% of FMF pts display disease activity despite colchicine treatment. The treatment is generally under-dosed, especially in children. The adherence and the compliance to the treatment is generally good.