OBJECTIVE: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), 
a recombinant form of the naturally occurring interleukin 1 receptor antagonist, 
plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid 
arthritis (RA).
METHODS: Patients with active RA (n = 506) despite current treatment with MTX 
were enrolled in this multicentre, double blind, randomised, placebo controlled 
study. Patients received subcutaneous injections of anakinra 100 mg/day or 
placebo. They were assessed monthly for 6 months for improvement in signs and 
symptoms of RA and for adverse events. The primary efficacy measure was the 
percentage of patients attaining ACR20 response at week 24.
RESULTS: Significantly greater proportions of patients treated with anakinra 
compared with placebo achieved ACR20 (38% v 22%; p<0.001), ACR50 (17% v 8%; 
p<0.01), and ACR70 (6% v 2%; p<0.05) responses. The response to anakinra was 
rapid; the proportion of patients with an ACR20 response at the first study 
assessment (4 weeks) was twice as high with anakinra as with placebo (p<0.005). 
Clinically meaningful and statistically significant responses were also seen in 
individual components of the ACR response (for example, Health Assessment 
Questionnaire, pain, C reactive protein levels, and erythrocyte sedimentation 
rate). Anakinra was well tolerated, with a safety profile, similar to that of 
placebo with one exception: mild to moderate injection site reactions were more 
common with anakinra than with placebo (65% v 24%).
CONCLUSIONS: This study confirms previous observations from a dose-ranging study 
showing that anakinra, in combination with MTX, is an effective and safe 
treatment for patients with RA who have inadequate responses to MTX alone.