Pericardial late gadolinium enhancement and time to recurrence: a substudy from RHAPSODY, a phase 3 clinical trial of rilonacept in recurrent pericarditis
Paul Cremer, David Lin, Sushil Allen Luis, John W. Petersen, Antonio Abbate, Christine Jellis, Debbie Kwon, Antonio Brucato, Fang Fang, Antonella Insalaco, Martin M. LeWinter, Basil S. Lewis, Liangxing Zou, Stephen J. Nicholls, Allan L. Klein, Massimo Imazio, John F. Paolini, RHAPSODY Investigators, Antonio Abbate, Wael Abo‐Auda, Asif Akhtar, Michael Arad, Shaul Atar, Bipul Baibhav, Karan Bhalla, Antonio Brucato, Sean P. Collins, David Colquhoun, Paul Cremer, David Cross, Girish Dwivedi, Alon Eisen, NAHUM A. FREEDBERG, Shmuel Fuchs, Eliyazar Gaddam, Marco Gattorno, Eli V. Gelfand, Paul Grena, Majdi Halabi, David C.H. Harris, Massimo Imazio, Antonella Insalaco, Amin Karim, Allan L. Klein, Kirk U. Knowlton, Apostolos Kontzias, Robert Kornberg, Faisal Latif, David Leibowitz, Martin M. LeWinter, David Lin, Dor Lotan, Pey Wen Lou, Sushil Allen Luis, Mady Moriel, Stephen J. Nicholls, John W. Petersen, Michael A. Portman, Philip Roberts‐Thomson, Elad Schiff, Robert Siegel, Michael B. Stokes, Paul Sutej, Samuel G. Wittekind, Valentin Witzling, Robert Zukermann
Abstract
Abstract Aims 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. Methods and results 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 (n = 9), patients with moderate or severe pericardial LGE (n = 16) generally had a higher number of recurrent episodes per year (5.3 vs. 3.9) and a higher mean CRP level (3.6 vs. 1.1 mg/dL). Overall, 10/14 (71.4%) who received a placebo had a recurrence compared to 0/11 (0%) who received rilonacept. In patients randomized to placebo who had moderate or severe pericardial LGE, the median time to recurrence was 4.2 weeks compared to 10.7 weeks in patients who had trace or mild pericardial LGE. At the conclusion of the event-driven randomized-withdrawal period, among patients receiving a placebo, 5/7 (71.4%) with trace or mild pericardial LGE and 5/7 (71.4%) with moderate or severe pericardial LGE had a recurrence. Conclusions 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. ClinicalTrials.gov Identifier NCT03737110