Phase 3 trial of interleukin-1 trap rilonacept in recurrent pericarditis: New England Journal of Medicine

A.L. Klein, M. Imazio, P. Cremer, A. Brucato, A. Abbate, F. Fang, A. Insalaco, M. LeWinter, B.S. Lewis, D. Lin, S.A. Luis, S.J. Nicholls, A. Pano, A. Wheeler, J.F. Paolini, RHAPSODY Investigators

Research output: Contribution to journalArticlepeer-review


BACKGROUND Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis. METHODS We conducted a phase 3 multicenter, 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). 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 had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed. RESULTS A total of 86 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 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; 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
Original languageEnglish
Pages (from-to)31-41
Number of pages11
JournalNew Engl. J. Med.
Issue number1
Publication statusPublished - 2021


  • C reactive protein
  • interleukin 1
  • low density lipoprotein cholesterol
  • placebo
  • rilonacept
  • triacylglycerol
  • fusion protein
  • IL1A protein, human
  • IL1B protein, human
  • interleukin 1 receptor type I
  • interleukin 1alpha
  • interleukin 1beta
  • adolescent
  • adult
  • aged
  • allergic pneumonitis
  • alopecia
  • Article
  • child
  • confidence interval
  • controlled study
  • double blind procedure
  • drug efficacy
  • drug hypersensitivity
  • drug response
  • drug safety
  • drug withdrawal
  • erythema
  • female
  • hazard ratio
  • human
  • injection site reaction
  • loading drug dose
  • low density lipoprotein cholesterol level
  • major clinical study
  • male
  • monotherapy
  • multicenter study
  • pain
  • pericarditis
  • phase 3 clinical trial
  • priority journal
  • protein blood level
  • randomized controlled trial
  • recurrent disease
  • side effect
  • symptom
  • triacylglycerol level
  • upper respiratory tract infection
  • adverse event
  • clinical trial
  • middle aged
  • proportional hazards model
  • respiratory tract infection
  • subcutaneous drug administration
  • young adult
  • Adolescent
  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interleukin-1alpha
  • Interleukin-1beta
  • Male
  • Middle Aged
  • Pericarditis
  • Proportional Hazards Models
  • Receptors, Interleukin-1 Type I
  • Recombinant Fusion Proteins
  • Recurrence
  • Respiratory Tract Infections
  • Young Adult


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