Which Definition Should be used to Determine Colchicine Resistance Among Patients with Familial Mediterranean Fever?

Abstract

Objectives: Colchicine is the main therapy for familial Mediterranean fever (FMF); however, 5-10% of patients are colchicine-resistant. There is no standard and validated definition for colchicine resistance. We aimed to compare the existing definitions for colchicine resistance in both adult and paediatric FMF patients to find out the best definition to determine colchicine-resistant patients.

Methods: 385 FMF patients were evaluated and patients receiving anti-interleukin-1 treatment were included. The anti-IL-1 therapy had been initiated by the experts in the past based on their experience. Eleven different definitions (found out after PubMed search for colchicine resistance in FMF) were applied to all patients. Results were re-analysed after excluding the patients who had no clinical attacks but persistently high acute phase reactants (APRs) and/or amyloidosis.

Results: Sixty patients (40 adults/20 children) who had been using anti-IL-1 therapy were included into this study as colchicine-resistant patients. The highest percentage of patients fulfilled definition 5 (93.3%). Definition 9 had the poorest performance (26%). Significantly, a higher percentage of adult patients met definitions 4 and 6 than paediatric patients (87.5% vs. 50%, p=0.002; 75% vs. 40%, p=0.008, respectively). After excluding patients without clinical attacks, the highest percentage of patients fulfilled definition 2 (94.4%). We combined the attack frequency (>1 typical episode/3 months) in definition 2 and presence of amyloidosis/APR increase (increase in ≥2/3 APRs) in definition 5 to create a new definition which was met by 59 (98.3%) colchicine-resistant FMF patients.

Conclusions: Definition of colchicine resistance is still controversial. Definitions with both clinical and laboratory criteria were met by a higher percentage of resistant patients than those without laboratory criteria. However, the proper definitions for the attack-free period and persistence of APRs are still lacking.