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

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). We examine how the definition of colchicine resistance has evolved along with various characteristics of colchicine that may help explain unresponsiveness to the drug. 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. These results underscore the need to identify patients who are not optimally managed with colchicine and who might therefore benefit from additional biologic therapies.