Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharmacokinetic, and socioeconomic characterization.

OBJECTIVES: To identify the ethnic, clinical, genetic, and pharmacokinetic correlates of colchicine treatment failure in patients with familial Mediterranean fever (FMF).

METHODS: Fifty-nine FMF patients, unresponsive to a daily dose of > or =2 mg colchicine, were compared with 51 colchicine-responsive patients by clinical, demographic, and socioeconomic assessment, FMF gene (MEditerranean FeVer [MEFV]) mutation and serum amyloid A1 (SAA1) gene polymorphism analysis, and plasma and white blood cell colchicine level determination.

RESULTS: Colchicine responders and nonresponders were comparable with respect to gender, age, duration and onset of the disease, and various demographic parameters. The 2 cohorts were found to carry mainly the M694V MEFV mutation and had a similar number of homozygotes or compound heterozygotes. Predominance of the alpha/beta alleles of SAA1 and comparable plasma and polymorphonuclear colchicine concentrations characterized both groups. Nonresponders were from lower socioeconomic backgrounds, had less education, and a more severe form of disease. A statistically significant 2-fold elevation of colchicine concentration in the mononuclear cells (MNC) of responders was found.

CONCLUSIONS: Colchicine treatment failure in FMF is associated with inadequate colchicine MNC concentration, probably resulting from a genetic defect unrelated to the underlying FMF.