A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

• Published in: Annals of the rheumatic diseases Vol. 63; no. 9; pp. 1062 - 1068
• Main Authors: Cohen, S B, Moreland, L W, Cush, J J, Greenwald, M W, Block, S, Shergy, W J, Hanrahan, P S, Kraishi, M M, Patel, A, Sun, G, Bear, M B
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01-09-2004; BMJ; BMJ Publishing Group LTD
• Subjects: ACR; American College of Rheumatology; anakinra; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; Biological and medical sciences; C reactive protein; CRP; Cytokines; disease modifying antirheumatic drugs; Diseases of the osteoarticular system; DMARDs; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Drug Therapy, Combination; erythrocyte sedimentation rate; ESR; Extended Report; Female; Gangrene; HAQ; Health Assessment Questionnaire; Humans; IL1Ra; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Inflammatory joint diseases; injection site reaction; interleukin; interleukin 1 receptor antagonist; Interleukin 1 Receptor Antagonist Protein; ISR; Male; Medical sciences; Methotrexate; Methotrexate - adverse effects; Methotrexate - therapeutic use; Middle Aged; MTX; Pain; Quality of life; Receptors, Interleukin-1 - antagonists & inhibitors; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Rheumatoid arthritis; Severity of Illness Index; Sialoglycoproteins - adverse effects; Sialoglycoproteins - therapeutic use; Studies; Tumor necrosis factor-TNF; Antineoplastic agent; Human; Immunopathology; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Antifolate; Immunomodulator; Chronic; Treatment; Antimetabolic; Rheumatoid arthritis; Interleukin 1; Double blind study; Antagonist; Methotrexate; Anakinra; Biological receptor
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2003.016014

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.