Clinical Pearls & Morning Reports
Klein et al. conducted a phase 3, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Read the NEJM Original Article here.
Q: How common is recurrent pericarditis?
A: Recurrent pericarditis is a disease characterized by chronic and debilitating pericardial inflammation, with wide-ranging effects on physical function, well-being, and productivity, in addition to considerable demands on health care resources. Approximately 15 to 30% of patients who have an initial pericarditis episode will have a recurrence despite treatment with colchicine. Among the limited therapeutic options available, glucocorticoids are of particular concern because of nonspecific immunosuppression and because of the risk of serious adverse events associated with long-term use.
Q: What is rilonacept and why might it lower the risk of recurrent pericarditis?
A: Interleukin-1 has been implicated in the pathophysiology of recurrent pericarditis and is a viable target for intervention in patients who have evidence of systemic inflammation (e.g., elevated CRP levels). The potential of interleukin-1 inhibition was evaluated in a trial of the recombinant interleukin-1–receptor antagonist anakinra in a small number of patients with colchicine-resistant idiopathic recurrent pericarditis who had previously had pericarditis recurrence after the withdrawal of glucocorticoids; many of the patients continued using colchicine during that trial. A subsequent phase 2 trial of rilonacept, an interleukin-1α and interleukin-1β cytokine trap, provided early evidence of resolution of pericardial inflammation.
A: In this trial, patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who met prespecified response criteria were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. Rilonacept led to a lower risk of pericarditis recurrence than placebo (hazard ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, in the intention-to-treat population, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence event, as compared with 23 of 31 patients (74%) in the placebo group. The findings with regard to the primary efficacy end point were consistent regardless of baseline glucocorticoid use. All three major secondary efficacy end points (assessed at week 16 of the randomized-withdrawal period) showed a benefit of rilonacept monotherapy in providing a sustained clinical response and reducing the symptoms of pericarditis.
A: The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections. All the upper respiratory tract infections were mild or moderate in severity. In addition, higher lipid levels, as assessed in patients who were in a nonfasting state, were observed with rilonacept than with placebo, as has been reported elsewhere.