Long‐term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin‐1 receptor antagonist) in patients with rheumatoid arthritis: Extension phase of a randomized, double‐blind, placebo‐controlled trial

Abstract

Objective. To demonstrate the long-term efficacy of anakinra, a human recombinant interleukin-1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long-term safety of anakinra at different daily doses.Methods. The efficacy and safety of anakinra were previously demonstrated in a double-blind, placebocontrolled, 24-week evaluation in 472 patients with active RA. Of 345 patients who completed the placebocontrolled phase of the study, 309 continued in a 52-week, multicenter, double-blind, parallel-group extension phase of the study. Patients received subcutaneous injections of anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52-week extension phase (76 weeks total exposure).Results. A total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24-week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment-related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended anakinra therapy.Conclusion. The clinical benefits of treatment with daily self-administered subcutaneous injections of anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long-term use of anakinra for the treatment of patients with RA.

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

“…Anakinra, a recombinant IL-1ra, has demonstrated efficacy in reducing the symptoms of RA (alone or in combination with methotrexate) in randomized controlled trials in adults [16][17][18] and in small uncontrolled studies of children with JRA [19,20]. Treatment of RA patients with anakinra has resulted in decreased radiographic progression and beneficial effects on disease activity.…”

Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations

“…Interleukin-1 receptor antagonist has proved safe in patients with sepsis (Fisher et al, 1994), and is licensed for clinical use in rheumatoid arthritis (Nuki et al, 2002). We have tested its safety in a small, randomized, double-blinded study, where IL-1RA was administered as an intravenous bolus, followed by infusion, to patients within 6 h of stroke compared with placebo (Emsley et al, 2005).…”

Targeting IL-15 Receptor-Bearing Cells with an Antagonist Mutant IL-15/Fc Protein Prevents Disease Development and Progression in Murine Collagen-Induced Arthritis

“…The dysregulated intra-articular expression of proinflammatory cytokines, in particular, TNF-␣ and IL-1␤, plays a key role in the pathogenesis of RA (1), a finding that has been corroborated by the successful treatment of RA patients with therapeutic agents targeted at inhibiting the activity of either of these cytokines (2)(3)(4)(5)(6)(7). Although often successful in clinical practice, blocking, for instance, TNF-␣ is not effective in all patients and does not lead to a remission of the disease.…”