Seza Ozen1, Isabelle Kone-Paut2, Ahmet Gül3. 1. Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. Electronic address: sezaozen@hacettepe.edu.tr. 2. Paediatric Rheumatology Department, CEREMAI, Université Paris SUD, Hôpital de Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin Bicêtre, Paris, France. 3. Department of Internal Medicine, Division of Rheumatology, Istanbul University Faculty of Medicine, Istanbul, Turkey.
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.
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.