Abstract
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 language | English |
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Pages (from-to) | 31-41 |
Number of pages | 11 |
Journal | New Engl. J. Med. |
Volume | 384 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2021 |
Keywords
- 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