Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharmacokinetic, and socioeconomic characterization.
OBJECTIVE
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.
Lidar
Merav
M
Heller Institute of Medical Research, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel.
Scherrmann
Jean-Michel
JM
Shinar
Yael
Y
Chetrit
Angela
A
Niel
Elisabeth
E
Gershoni-Baruch
Ruth
R
Langevitz
Pnina
P
Livneh
Avi
A
D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003078:Colchicine / Q000627:therapeutic use*; D010505:Familial Mediterranean Fever / Q000188:drug therapy* / Q000235:genetics*; D005808:Genes, Recessive; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D000685:Serum Amyloid A Protein / Q000235:genetics*; D012959:Socioeconomic Factors; D017211:Treatment Failure
D006074:Gout Suppressants; D000685:Serum Amyloid A Protein; D003078:Colchicine