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Rilonacept reduces risk of pericarditis recurrence

Presented by
Dr Alan Klein, Cleveland Clinic, USA
AHA 2020
In patients with symptomatic recurrent pericarditis failing standard of care, addition of the interleukin (IL) 1α/1β inhibitor rilonacept resolved pericarditis episodes in the RHAPSODY trial. Rilonacept monotherapy reduced the risk of pericarditis recurrence by 96%. The treatment also had corticosteroid-sparing effects and improved quality of life [1,2].

Dr Alan Klein (Cleveland Clinic, USA) presented the main results of the RHAPSODY trial (NCT03737110). As Dr Klein explained, recurrent pericarditis is a debilitating disease with no (FDA) approved therapies; typically a combination of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and steroids is given. In the long run, steroids are associated with significant morbidity. IL-1 has been implicated as a key mediator in recurrent pericarditis. Rilonacept is a subcutaneous, once-weekly IL-1α and IL-1β cytokine trap.

RHAPSODY was a phase 3, multicentre, double-blind, event-driven, randomised withdrawal trial of rilonacept. Acutely symptomatic patients failing their background regimen (n=86) received rilonacept 320 mg, followed by a run-in period with rilonacept 160 mg weekly for 12 weeks (during which background medication was tapered), after which clinical responders were randomised to rilonacept 160 mg weekly monotherapy (n=30) versus placebo (n=31). The primary efficacy endpoint was time to first adjudicated pericarditis recurrence. Dr Klein stressed that enrolled patients were representative of the real-world pericarditis population.

Rilonacept initiation resulted in rapid resolution of acute pericarditis episodes. Pain numerical rating scale  and C-reactive protein (CRP) rapidly decreased after the first dose of rilonacept. All patients on corticosteroids successfully tapered and transitioned to monotherapy rilonacept during the run-in. The primary outcome occurred in 2 of 30 (6.7%) of patients in the rilonacept group and in 23 of 31 (74.2%) in the placebo group (P<0.0001). Median number of weeks to recurrence in the rilonacept group could not be calculated due to the number of events being too low; in the placebo group it was 8.6 weeks (95% CI 4.0–11.7); HR 0.04 (95% CI 0.01–0.18; P<0.001; see Figure). The 2 events in the rilonacept arm both occurred after brief, temporary drug interruptions.

Figure: Rilonacept significantly reduced risk of pericarditis recurrence [1]

The rates of 3 secondary efficacy endpoints were statistically highly significantly in favour of rilonacept:

      • the proportion of patients that maintained clinical response at week 16 was 81% in the rilonacept group versus 20% in the placebo group (P=0.0002);
      • the proportion of patients with absent/minimal pericarditis symptoms (based on the 6-point Patient Global Impression of Pericarditis Severity [PGIPS] at week 16) was 81% and 25%, respectively (P=0.0006); and
      • the percentage of days with no/minimal pain in the first 16 weeks was 98% and 46%, respectively (P=0.0001).

Rilonacept was generally well-tolerated with no drug-related serious adverse events or deaths. In the run-in period, 4 patients discontinued rilonacept therapy due to adverse events. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections.

    1. Klein AL. RHAPSODY: Rilonacept an IL-1α and IL-1β Trap Resolves Pericarditis Episodes and Reduces Risk of Recurrence in a Phase 3 Trial of Patients With Recurrent Pericarditis. LBS.07, AHA Scientific Sessions 2020, 13–17 Nov.
    2. Klein AL, et al. N Engl J Med 2021;384:31–41.


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