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- IL, interleukin
- RA rheumatoid arthritis
- MTX, methotrexate
- HAQ, Health Assessment Questionnaire
- ACR, American College of Rheumatology
Interleukin 1 (IL1) plays a central part in the pathophysiology of rheumatoid arthritis (RA).1,2 The IL1 gene family includes IL1α, IL1β, and IL1 receptor antagonist (IL1Ra). IL1α and IL1β are both agonist molecules. There are two distinct IL1 receptors, designated type I (IL1RI) and type II (IL1RII). IL1 binding to IL1RI results in signal transduction and cell activation. IL1Ra is the third member of the IL1 gene family. The agonistic effects of IL1 are partially blocked by the interaction between IL1Ra and IL1RI. When IL1Ra binds to IL1RI, it blocks the binding of IL1α and IL1β and inhibits signal transduction. Recombinant human IL1Ra, anakinra, has been approved for the treatment of patients with rheumatoid arthritis (RA).
Conventional response criteria
Five randomised, placebo controlled clinical trials of anakinra in RA have been completed (table 1). A total of 2932 patients were recruited. In four studies, the primary end points were related to clinical efficacy. The primary outcome measures in the fifth were related to safety. Both the European monotherapy and the methotrexate (MTX) combination therapy studies have been published.3,4 A treatment effect was not observed in the low dose monotherapy study. Radiographic analyses are being completed in the confirmatory efficacy study.
In the European monotherapy study, the onset of action was early in the three treatment groups, and a clinical effect was seen as early as two weeks (fig 1). The clinical effect continued to increase throughout the study, and an American College of Rheumatology (ACR) 20% response5 was observed in 43% of the 116 patients who were randomised to receive 150 mg/day anakinra, compared with 27% of the 121 patients who received placebo (p=0.014). Significant improvements were observed in each of the individual components of the ACR response in the patients who …
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