Interventions for reducing inflammation in familial Mediterranean fever.

BACKGROUND Familial Mediterranean fever, a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine as a potential drug for preventing attacks of familial Mediterranean f... show more

BACKGROUND Familial Mediterranean fever, a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine as a potential drug for preventing attacks of familial Mediterranean fever. For those people who are colchicine-resistant or intolerant, drugs such as rilonacept, anakinra, etanercept, infliximab, thalidomide and interferon-alpha might be beneficial. OBJECTIVES To evaluate the efficacy and safety of interventions for reducing inflammation in people with familial Mediterranean fever. SEARCH METHODS We used detailed search strategies to search the following databases: CENTRAL; MEDLINE; Embase; Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure Database (CNKI); Wan Fang; and VIP. In addition, we also searched the clinical trials registries including ClinicalTrials.gov, the International Standard Randomized Controlled Trial Number Register, the WHO International Clinical Trials Registry Platform and the Chinese Clinical Trial Registry, as well as references listed in relevant reports.Date of last search: 21 May 2014. SELECTION CRITERIA Randomized controlled studies of people with diagnosis of familial Mediterranean fever, comparing active interventions (including colchicine, anakinra, rilonacept, etanercept, infliximab, thalidomide, interferon-alpha, ImmunoGuard™ (a herbal dietary supplement) and non-steroidal anti-inflammatory drugs) with placebo or no treatment, or comparing active drugs to each other. DATA COLLECTION AND ANALYSIS The authors independently selected studies, extracted data and assessed risk of bias. We pooled data to present the risk ratio or mean difference with their 95% confidence intervals. We assessed overall evidence quality according to the GRADE approach. MAIN RESULTS We included four randomized placebo-controlled studies with a total of 75 participants (aged three to 53 years); three were of cross-over and one of parallel design. Two studies used the active intervention of oral colchicine (0.6 mg three times daily or 0.5 mg twice daily), one study used oral ImmunoGuard™ and the fourth used rilonacept as a subcutaneous injection. The duration of each study arm ranged from one to three months.The two most recent studies were generally well-designed, except for an unclear risk of detection bias in one of these. However, some inadequacy existed in the other two older studies, where each had an unclear risk of selection bias, a high risk of attrition bias, an unclear risk of reporting bias and a high risk of other potential bias (baseline characteristics such as mutation status and disease severity were not described); one of these studies additionally had an unclear risk of detection bias.We aimed to report on the number of participants experiencing an attack, the timing of attacks, any adverse drug reactions and the response of a number of biochemical markers from the acute phase of an attack, but data were not available for all outcomes across all comparisons.Based on one study (15 participants), there was a significant reduction in the number of people experiencing attacks at three months when colchicine was administered at a dose of 0.6 mg three times daily (14% versus 100%), risk ratio 0.21 (95% confidence interval 0.05 to 0.95); however, the GRADE evidence quality was low. Based on two further studies, there was no significant reduction in the number of participants experiencing attacks at two months when colchicine was administered at a dose of 0.5 mg twice daily (22 participants) in people with familial Mediterranean fever, or at three months when rilonacept was used in individuals who were colchicine-resistant or colchicine-intolerant (14 participants). In the ImmunoGuard™ study (24 participants) acute phase response indicators (including erythrocyte sedimentation rate, white blood cell count and C-reactive protein) were not reduced after one month treatment. AUTHORS' CONCLUSIONS There were limited randomized controlled studies assessing interventions for people with familial Mediterranean fever. Based on the evidence, colchicine appears to reduce the number of people experiencing attacks; however, only a few low-quality randomized controlled studies contributed data for analysis. Further randomized controlled studies examining active interventions, not only colchicine, are necessary before a comprehensive conclusion regarding the efficacy and safety of interventions for reducing inflammation in familial Mediterranean fever can be drawn. show less