Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments

• Published in: Seminars in arthritis and rheumatism 2017-08, Vol.47 (1), p.115-120
• Main Authors: Ozen, Seza, MD, Kone-Paut, Isabelle, MD, Gül, Ahmet, MD
• Format: Article
• Language: English
• Subjects: Colchicine - administration & dosage; Colchicine - adverse effects; Colchicine - pharmacology; Colchicine resistance; Drug Resistance - genetics; Drug Tolerance - genetics; Familial Mediterranean fever; Familial Mediterranean Fever - drug therapy; Familial Mediterranean Fever - genetics; Female; Humans; Interleukin-1; Male; Medication Adherence; Rheumatology; Second-line therapy; Therapeutics
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2017.03.006

Abstract Background Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory syndrome characterized by recurrent serositis or arthritis attacks and, in some patients, chronic subclinical inflammation that predisposes to secondary amyloidosis. Colchicine is the gold standard of treatment, which reduces attack frequency and amyloidosis risk. However, up to 5% of patients are considered resistant or inadequately respond to colchicine, and some others cannot tolerate the side effects of effective doses of colchicine (colchicine intolerant). Methods We examine how the definition of colchicine resistance has evolved along with various characteristics of colchicine that may help explain unresponsiveness to the drug. Results Key factors in assessing colchicine resistance include attack frequency and severity, levels of acute phase reactants, colchicine dosage and composition, and treatment compliance. Promising clinical results have been obtained with biologics targeting interleukin-1 in colchicine-resistant or -intolerant patients with FMF. Conclusions These results underscore the need to identify patients who are not optimally managed with colchicine and who might therefore benefit from additional biologic therapies.