Pericardial late gadolinium enhancement and time to recurrence: a substudy from RHAPSODY, a phase 3 clinical trial of rilonacept in recurrent pericarditis.

In this protocol-predefined substudy of the RHAPSODY trial, the primary aim was to assess whether pericardial late gadolinium enhancement (LGE) was associated with time to pericarditis recurrence. RHAPSODY was a Phase 3 double-blind, placebo-controlled, randomized-withdrawal trial that demonstrated the efficacy of rilonacept in recurrent pericarditis (RP). Patients with a history of multiple RP and an active recurrence were enrolled and had the option to participate in a cardiac magnetic resonance (CMR) imaging substudy. CMRs were interpreted by a blinded independent core laboratory with prespecified criteria to define pericardial LGE. Compared to patients with trace or mild pericardial LGE ( Among patients with multiple RP, these preliminary findings support the concept of pericardial LGE as an imaging biomarker that may inform the duration of treatment and risk of recurrence with cessation of therapy and larger studies should be considered. NCT03737110. Patients with recurrent pericarditis (RP) can suffer from debilitating pain and a poor quality of life. Rilonacept blocks interleukin 1 (IL-1), the major inflammatory driver of RP, and is highly effective at treating active episodes of RP and preventing recurrence. In pericarditis, there is the recruitment of blood vessels to the pericardium, and the extent of these new blood vessels tracks with the degree of inflammation. Cardiac magnetic resonance imaging (CMR) readily images this blood supply and can therefore assess inflammation by the magnitude of pericardial late gadolinium enhancement (LGE). In this study of RP patients with CMR, no patients who continued rilonacept had a recurrence compared to 10/14 (71.4%) patients who stopped rilonacept and received a placebo. In the patients who received a placebo, the rate of eventual recurrence was similar among patients with trace or mild pericardial LGE at baseline (5/7) compared to patients with moderate or severe pericardial LGE at baseline (5/7). However, patients who demonstrated moderate or severe pericardial LGE had a faster recurrence (∼4 weeks after stopping rilonacept) compared to patients with trace or mild pericardial LGE (∼11 weeks after stopping rilonacept). These results suggest that pericardial LGE can serve as an imaging biomarker to assess the severity of RP and raise the possibility that CMR could be studied in future clinical trials to determine appropriate therapy and treatment duration in patients with RP.

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© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Déclaration de conflit d'intérêts

P.C. Cremer: Cremer reports grants and personal fees from Kiniksa Pharmaceuticals; grants from Novartis Pharmaceuticals; and personal fees from SOBI Pharmaceuticals outside the submitted work. D. Lin: None. S.A. Luis: Luis reports consultant fees for Kiniksa Pharmaceuticals, SOBI Pharmaceuticals, and Medtronic. J. Petersen: None. A. Abbate: Abbate reports grants and personal fees from Kiniksa Pharmaceuticals during the conduct of the study; grants and personal fees from Olatec, Serpin, Novartis, and Janssen; and personal fees from Novo-Nordisk and Cromos Pharma outside the submitted work. C.L. Jellis: None. D. Kwon: None. A. Brucato: Brucato reports institutional funding from Kiniksa Pharmaceuticals as an investigative site; an unrestricted research grant from SOBI and ACARPIA; and travel and accommodation for the advisory committee from SOBI and Kiniksa Pharmaceuticals. F. Fang: Fang reports personal fees and others from Kiniksa Pharmaceuticals outside the submitted work at the time the study was conducted. A. Insalaco: Insalaco reports personal fees from SOBI. M. LeWinter: LeWinter reports grants and advisory board, consulting, and other fees from Kiniksa Pharmaceuticals outside the submitted work and consulting fees from SOBI Pharmaceuticals outside the submitted work. B.S. Lewis: Lewis reports personal fees from Kiniksa Pharmaceuticals during the conduct of the study. L. Zou: Zou reports personal fees and others from Kiniksa Pharmaceuticals outside the submitted work. S.J. Nicholls: Nicholls reports grants and personal fees from Kiniksa Pharmaceuticals during the conduct of the study; grants and personal fees from AstraZeneca, Anthera, Resverlogix, Sanofi-Regeneron, and Esperion; personal fees from Akcea, Eli Lilly, Omthera, Merck, Takeda, CSL Behring, and Boehringer Ingelheim; and grants from Amgen, Novartis, Abionyx (formerly Cerenis), The Medicines Company, Liposcience, Roche, and InfraReDx outside the submitted work. A.L. Klein: Klein reports grants and others from Kiniksa Pharmaceuticals during the conduct of the study and other fees from Cardiol Therapeutics, SOBI Pharmaceuticals, and Pfizer Pharmaceuticals outside the submitted work. M. Imazio: Imazio reports no disclosures. J.F. Paolini: Paolini reports personal fees and others from Kiniksa Pharmaceuticals outside the submitted work and is a patent inventor on pending patent applications licensed to Kiniksa Pharmaceuticals covering methods of using rilonacept for treating RP.