Rilonacept reduces risk of pericarditis recurrence

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:

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    • 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.

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   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.

 



Posted on 18 February 202119 February 2021