Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

Abstract

BACKGROUND:

Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment.

METHODS AND RESULTS:

Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001).

CONCLUSIONS:

In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence.

REGISTRATION:

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

• Authors: Massimo Imazio, Allan L Klein, Antonio Brucato, Antonio Abbate, Michael Arad, Paul C Cremer, Antonella Insalaco, Martin M LeWinter, Basil S Lewis, David Lin, Sushil A Luis, Stephen J Nicholls, Paul Sutej, Yishay Wasserstrum, JoAnn Clair, Indra Agarwal, Sheldon Wang, John F Paolini, RHAPSODY Investigators
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 13 Issue 6 Pg. e032516 (Mar 19 2024) ISSN: 2047-9980 [Electronic] England
• PMID: 38471825 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Interleukin-1alpha
• Recombinant Fusion Proteins
• rilonacept

Topics

• Humans
• Interleukin-1alpha
• Pericarditis (drug therapy, epidemiology)
• Recombinant Fusion Proteins (adverse effects)
• Recurrence
• Risk Reduction Behavior
• Treatment Outcome