Objective:Colchicine is the mainstay treatment for Familial Mediterranean Fever (FMF). However 5% to 10% of the patients with FMF are unresponsive or intolerant to colchicine. Biologics are efficient in many rheumatic diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, cryopyrin-associated periodic syndromes. We performed a systematic review to analyze patients with FMF, including juvenile patients who received treatment with biologics.Methods:A MEDLINE search, including articles published in English language between 1990 and May 2012, was performed. Patients who had Mediterranean fever variants but could not be classified as FMF according to Tel-Hashomer criteria were excluded.Results:There is no controlled trial on the efficacy and safety of biologics in FMF. Fifty-nine (32 female and 27 male) patients with FMF who had been treated with biologics (infliximab, etanercept, adalimumab, anakinra, and canakinumab) were reported in 24 single reports and 7 case series. There were 16 children and 43 adults (7- to 68-year olds). Five patients were reported to have colchicine intolerance or had adverse events related to colchicine use, and the rest 54 were unresponsive to colchicine treatment.Conclusions:The current data are limited to case reports, and it is difficult to obtain a quantitative evaluation of response to biologic treatments. However, on the basis of reported cases, biologic agents seem to be an alternative treatment for patients with FMF who are unresponsive or intolerant to colchicine therapy and seem to be safe. Controlled studies are needed to better evaluate the safety and efficacy of biologics in the treatment of patients with FMF.