Anakinra: review of recombinant human interleukin-I receptor antagonist in the treatment of rheumatoid arthritis.
BACKGROUND
Interleukin-1 (IL-1) plays an important role in the pathophysiology and progression of rheumatoid arthritis (RA) by contributing to destruction of cartilage, bone, and periarticular tissues. Inhibiting IL-1 synthesis or activity with the use of recombinant human IL-1 receptor antagonist (anakinra) may prove to be an effective approach to the treatment of RA.


OBJECTIVE
The purpose of this article is to review the effects of anakinra in the treatment of RA.


METHODS
A MEDLINE search from 1982 to 2003 was used to identify animal studies and randomized clinical trials of anakinra and other therapies that target IL-1.


RESULTS
Clinical trials of anakinra have shown that it reduces the signs and symptoms of active disease and slows the rate of radiographic destruction in adults with RA. With anakinra 150 mg/d, 43% of patients achieved an American College of Rheumatology (ACR) 20% response, compared with 27% with placebo (P = 0.014). The ACR20 score indicates at least 20% improvement in the ACR composite score, which includes assessment of tender and swollen joint count, and other clinical end points such as pain and disability assessment. Patients treated with anakinra also experienced a 59% reduction in new bony erosion compared with controls (P < 0.001) and a 65% reduction in joint space narrowing as measured by the modified Sharp score (P = 0.020). Injection-site reactions were the most commonly reported adverse event, occurring in 50%, 73%, and 81% of patients receiving anakinra 30, 75, and 150 mg/d, respectively, compared with 25% of patients receiving placebo. Few serious adverse events were reported, and they typically occurred in patients receiving the highest daily dosage.


CONCLUSIONS
IL-1 is an important cytokine in promoting the damage associated with RA. Anakinra is mildly to moderately effective and well tolerated in patients with active RA when used as monotherapy or in combination with methotrexate.
Furst
Daniel E
DE
Rheumatology Division, Geffen School of Medicine, University of California-Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90025-1670, USA. defurst@mednet.ucla.edu
D000328:Adult; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018501:Antirheumatic Agents; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D008727:Methotrexate