Long-term safety and maintenance of clinical improvement following treatment with KINERET

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Arthritis Rheum 2002 Nov;46(11):2838-46

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.

Nuki G, Bresnihan B, Bear MB, McCabe D.

University of Edinburgh, Edinburgh, Scotland, UK.

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,

placebo-controlled, 24-week evaluation in 472 patients with active RA.

Of 345 patients who completed the placebo-controlled 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.