A Cochrane review ¹ included 5 studies with a total of 2,876 subjects. Anakinra with or without other medical therapy for rheumatoid arthritis was compared with placebo. There was a 15% increase in patients achieving ACR20 with anakinra 50 to 150 mg daily (38%) versus placebo (23%) after 24 weeks. This is felt to be a clinically meaningful, though modest, outcome. An ACR20 (American College of Rheumatology) response is defined as a 20 per cent improvement in tender and swollen joint counts and the same level of improvement in three of the five following variables: patient/physician global assessments, pain scores, Stanford Health Assessment Questionnaire (HAQ score), and laboratory acute phase reactants. Other efficacy data all demonstrated significant improvement with anakinra as well. In subgroup analysis, improvement was noted for both studies comparing anakinra/placebo and anakinra/placebo + methotrexate (MTX) in ACR20 outcomes as well. The only study examining anakinra + etanercept + MTX versus placebo + etanercept + MTX. demonstrated no significant improvement in any outcome data.

There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo (number of withdrawals, deaths, total and serious adverse events, and total and serious infections). Injection site reactions were significantly increased (71% with anakinra versus 28% with placebo). 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%). The only study using a combination of biologic medications with anakira (anakinra + etanercept + MTX versus placebo + etanercept + MTX) did demonstrate significant increases in the number of withdrawals, injection site reactions, and serious adverse events, likely indicating the poor tolerability and increased risks associated with combining biologic therapies. Adverse event data for the long-term use of anakinra has yet to be assessed.

The authors state that although head to head comparison trials have not been carried out, the amount of improvement with anakinra is notably less when compared to studies using other biologic therapies (adalimumab, infliximab, and etanercept).

Comment: The quality of evidence is downgraded by study quality (more than 20% loss to follow up and inadequate intention-to-treat adherence).