¹ Department of Rheumatology, St Paul Medical Center, Dallas, Texas, USA
² Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Alabama, USA
³ Arthritis Consultation Center, Presbyterian Hospital of Dallas, Dallas, Texas, USA
⁴ Advances in Medicine, Rancho Mirage, California, USA
⁵ Private Practice, Bangor, Maine, USA
⁶ Rheumatology Associates of North Alabama, Huntsville, Alabama, USA
⁷ Goatcher CRU, SCGH, and RPH, Perth, Australia
⁸ St Clare’s Mercy Hospital, St Johns, Newfoundland, Canada
⁹ Amgen, Thousand Oaks, California, USA

Correspondence to:
Correspondence to:
Dr S B Cohen
Department of Rheumatology, St Paul Medical Center, 5939 Harry Hines Blvd, Suite 400, Dallas, TX 75235, USA; stanleycohen{at}radiantresearch.net

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.

Abbreviations: ACR, American College of Rheumatology; CRP, C reactive protein; DMARDs, disease modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; IL, interleukin; IL1Ra, interleukin 1 receptor antagonist; ISR, injection site reaction; MTX, methotrexate; RA, rheumatoid arthritis

Keywords: rheumatoid arthritis; anakinra; methotrexate; interleukin 1 receptor antagonist

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