The use of anakinra, an interleukin-1 receptor antagonist, in the treatment of rheumatoid arthritis

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Efficacy of anakinra

Efficacy results from several large, controlled studies support the use of anakinra for the signs and symptoms of RA. These results are summarized separately for each study.

Safety of anakinra

Randomized, placebo-controlled studies provided data on the safety of anakinra as a monotherapy [35], [39], in combination with MTX [36], [41], and with multiple DMARDs [37], [45].

Radiographic results

Because RA frequently leads to destructive lesions of cartilage and periarticular bone and IL-1 is a known mediator of joint damage, anakinra has the potential to inhibit structural damage. The trial that investigated anakinra as a monotherapy for signs and symptoms of RA [35] also evaluated the prevention of radiographic progression [38]. Hand and wrist radiographs were obtained at baseline and 24 weeks for the placebo-treated group and three anakinra-treated groups (30 mg/kg, 75 mg/kg, and

Anakinra plus etanercept

Although IL-1 is a known mediator of RA, TNF also plays a substantial role in its pathogenesis. Several clinical trials have investigated anti-TNF therapy and found it to be clinically efficacious in the treatment of RA [51], [52], [53], [54]. Because animal models had predicted the excellent clinical responses of anti–IL-1 and anti-TNF therapy in RA, the potential of synergistic effects of combination therapy that targeted both key cytokines (IL-1 and TNF) was investigated first in a rat model

Anakinra in patients who were previously treated with tumor necrosis factor

It was postulated that patients who have RA may have disease that is mediated by IL-1 and TNF or predominantly by one or the other, although definitive evidence for this hypothesis is lacking. An indication that patients may have IL-1–mediated disease is the inadequate response to anti-TNF therapy; these patients may respond successfully to anti–IL-1 therapy. To explore this hypothesis, an ad hoc analysis of a prospective study evaluated the efficacy of anakinra in patients who were treated

Summary

Anakinra has been proven safe and effective in the treatment of RA as monotherapy and in combination with other medications. The need for daily injectable administration has limited its use, as reflected by patient preference for less frequent dosaging from postmarketing surveillance. Thus, since FDA approval, anakinra primarily has been used as a secondary line of treatment for RA, following failures of other DMARDs or anti-TNF therapy.

Preclinical models, clinical trials, and postmarketing

Acknowledgements

The author thanks Cheri Osteen, PhD for editorial assistance.

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