Background: In the past decade, a novel class of therapies directed against specific cytokines implicated in the disease process of rheumatoid arthritis (RA), called the 'Biologics' have greatly improved and expanded treatment for RA. Anakinra is an interleukin-1 receptor antagonist that is currently FDA-approved for moderate-severe RA that has been unresponsive to initial disease-modifying anti-rheumatic drugs (DMARD) therapy. Objectives: To evaluate the clinical effectiveness and safety of anakinra in adult patients with rheumatoid arthritis. Search strategy: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1950 to Week 4 2008) , EMBASE (1980 to Week 5 2008), CINAHL (1982 to November 2007) and reference lists of articles. Selection criteria: Randomized controlled trials comparing anakinra alone or in combination with DMARDs or biologics to placebo or other DMARDs or biologics in patients >18 years old with rheumatoid arthritis. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Main results: Five trials involving 2876 patients, 781 randomized to placebo and 2065 to anakinra, were included. There was a significant improvement in number of participants achieving ACR20 (38% versus 23%) who were treated with anakinra 50 to 150 mg daily versus placebo after 24 weeks. This 15% increase in patients achieving ACR20 with anakinra versus placebo is felt to be a clinically meaningful, though modest, outcome. Other efficacy data - including ACR50 (18% versus 7%), ACR70 (7% versus 2%), HAQ, visual analog score (VAS), Larsen radiographic scores, and change in erythrocyte sedimentation rate (ESR) - all demonstrated significant improvement with anakinra 50 to 150 mg daily versus placebo as well. There were no statistically significant differences noted inmost safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively. The incidence of serious infections was clinically higher, but not statistically different, in the anakinra (25/1366 patients, 1.8%) versus placebo group (3/534 patients, 0.6%). Authors' conclusions: Anakinra is a relatively safe and modestly efficacious biologic therapy for rheumatoid arthritis. Although head to head comparison trials have not been carried out, the amount of improvement is notably less when compared to studies using other biologic therapies. More studies are needed to evaluate safety and efficacy, especially in comparison to other therapies, and adverse event data for the long-term use of Anakinra has yet to be assessed. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.