Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, 384(1), 31–41. https://doi.org/10.1056/NEJMoa2027892 Dr. Allan Klein et al.
Points
- Rilonacept, a cytokine trap that blocks interleukin-1α and interleukin-1β, was evaluated in phase 3 randomized-withdrawal trial for recurrent pericarditis treatment.
- Patients with acute symptoms of recurrent pericarditis and systemic inflammation were enrolled, and rilonacept was initiated after the run-in period, during which background medications were discontinued.
- The primary efficacy endpoint was the time to the first pericarditis recurrence, and safety was also assessed.
- Rilonacept led to rapid resolution of recurrent pericarditis episodes, and patients who received rilonacept monotherapy had a significantly lower risk of pericarditis recurrence than those who received a placebo.
- The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections.
Summary
Recurrent pericarditis, an inflammation of the sac surrounding the heart, has been linked to the cytokine interleukin-1 (IL-1). Rilonacept, an IL-1 cytokine trap that can block interleukin-1α and interleukin-1β, was evaluated in phase 3, randomized-withdrawal trial to assess its safety and efficacy in the treatment of recurrent pericarditis.
Patients with acute symptoms of recurrent pericarditis and systemic inflammation were enrolled, as indicated by an elevated C-reactive protein (CRP) level. Patients who experienced pericarditis recurrence while receiving standard therapy underwent a 12-week run-in period, during which rilonacept was initiated, and background medications were discontinued. Patients who responded positively were randomly assigned to receive continued rilonacept monotherapy or placebo in a 1:1 ratio. The primary efficacy endpoint was the time to the first pericarditis recurrence, assessed using a Cox proportional-hazards model, and safety was also assessed.
Eighty-six patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was five days, and the median time to normalize the CRP level was seven days. Sixty-one patients were randomly assigned, and during the randomized-withdrawal period, only 2 out of 30 patients (7%) in the rilonacept group had a pericarditis recurrence compared with 23 out of 31 patients (74%) in the placebo group. The median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections.
In conclusion, rilonacept was effective and safe in patients with recurrent pericarditis, resulting in a significantly lower risk of pericarditis recurrence than placebo. The study proves that targeting interleukin-1 with rilonacept can be a valuable treatment for patients with recurrent pericarditis.
Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2027892
References Klein, A. L., Imazio, M., Cremer, P., Brucato, A., Abbate, A., Fang, F., Insalaco, A., LeWinter, M., Lewis, B. S., Lin, D., Luis, S. A., Nicholls, S. J., Pano, A., Wheeler, A., & Paolini, J. F. (2021). Phase 3 trial of interleukin-1 trap rilonacept in recurrent pericarditis. New England Journal of Medicine, 384(1), 31–41. https://doi.org/10.1056/NEJMoa2027892
