Anakinra™(Kineret) is safe and well tolerated in RA patients with Comorbid Conditions
AnakinraTM (Kineret) is an interleukin-1 receptor antagonist approved for treatment in patients with rheumatoid arthritis (RA). In this study, Fleischmann et al (Arthritis Rheum 48:927, 2003) evaluated the safety and efficacy of anakinra in patients with and without comorbid conditions and in combination with conventional DMARDs. The preliminary results of this study have been summarized previously in our 2002 Eular Highlights where further details can be found.
Methods: In a large, randomized, placebo-controlled trial, the safety of anakinra was evaluated in 1,399 patients with RA. Patients were randomly assigned to receive daily subcutaneous injections of either 100 mg of anakinra or placebo. Patients were allowed to continue their disease-modifying antirheumatic drugs (DMARDs) except for anti-TNF agents which were discontinued. The anakinra- and placebo-treated groups were similar in terms of arthritis activity, comorbid conditions (asthma, COPD, , and concomitant medications/DMARDs.
Results: These data represent the first six months of the study. Serious adverse events occurred at a similar rate in the anakinra and placebo groups (7.7% and 7.8 %, respectively). The rate of all infectious events was 41.2% (460 of 1116) in patients treated with anakinra and 43.5% (123 of 283) in patients treated with placebo. There was a trend towards more serious infections in the anakinra group (n=23, 2.1%) compared to the placebo group (n=1, 0.4%), although this difference was not statistically significant (p=0.068). These infections were primarily pneumonias and cellulitis. There were no cases of reactivated tuberculosis or other opportunistic infections. An analysis of potential risk factors (e.g., specific comorbid conditions, duration of RA, concomitant medications, etc.) for these infections was conducted. None were significantly associated with increased risk for infection, although there was a trend towards more infections in patients with asthma.
Conclusions: Anakinra is safe and well tolerated in a diverse population of patients with RA, including those with comorbid conditions and those receiving single and multiple background DMARDs.
Editorial Comment: Anakinra (as monotherapy) has proven to be safer than the TNF antagonists in terms of opportunistic infections. Anakinra is a relatively weak and short-lived inhibitor of IL-1. It will be interesting to see the risk of infections if and when more potent IL-1 inhibitors are developed (e.g., IL-1 trap). It is also useful to remember that when anakinra and etanercept were combined in a preliminary open-label trial, there was a high rate of non-opportunistic infections. This combination should be avoided (as it was in the above study).