Reply to Albulushi et al.—Absence of Pericarditis Recurrence in Rilonacept-Treated Patients With COVID-19 and SARS-CoV-2 Vaccination: Results From RHAPSODY Long-term Extension

We thank Drs. Albulushi, Al-Jabri, and Al-Amri for their interest in our manuscript and appreciate the opportunity to provide additional clarity. The sample size is too small to make conclusions regarding the impact of different vaccine types on pericarditis recurrence rates. Most patients received mRNA vaccines, and only two patients received adenovirus-type vaccines. While SARS-CoV-2 vaccine impact on pericarditis recurrence cannot be assessed, it is important to note that no pericarditis recurrences were temporally associated with vaccination. Further, sustained rilonacept treatment led to sustained treatment response and reduced the risk of pericarditis recurrence by 98% beyond 18 months of treatment,1Imazio M. Klein A.L. Brucato A. et al.Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.J Am Heart Assoc. 2024; 13e032516https://doi.org/10.1161/JAHA.123.032516Crossref Scopus (2) Google Scholar regardless of vaccination status, whereas premature rilonacept cessation led to pericarditis recurrence. There were no pericarditis recurrences amongst vaccinated patients who continued rilonacept treatment. Among the 16 cases of COVID-19 in RHAPSODY LTE patients there was only one investigator-assessed recurrence, and that occurred 4.5 months after rilonacept cessation during the peri-COVID period in a partially vaccinated/ unvaccinated patient. Overall, we do not expect that the type of vaccine might influence the clinical outcomes of RP patients. The efficacy and safety of IL-1 pathway inhibition as a treatment of severe COVID-19 has not been established. As Dr Albulushi et al. have correctly stated, multiple cytokines, including IL-1, play an important role in the pathogenesis and disease progression following SARS-CoV-2 infection. A meta-analysis on the use of anakinra in severe COVID-19 has recently been published.2Mohamed Hussein A.A.R. Sayad R. Abdelshafi A. et al.A meta analysis on the utility of Anakinra in severe COVID-19 disease.Cytokine. 2023; 169156311https://doi.org/10.1016/j.cyto.2023.156311Crossref Scopus (0) Google Scholar Hussein et al. conclude that, though promising, in severe COVID-19 anakinra should be used with caution. It is important to note that a pericarditis recurrence could add complexity to the management of COVID-19, so even in the absence of a demonstrated benefit of IL-1 pathway inhibition for treating the cytokine storm associated with COVID-19, continued treatment with IL-1 pathway inhibition to prevent pericarditis recurrence should certainly limit the complexity of COVID-19 case management. After the last study visit of the RHAPSODY LTE, data collection into the trial database concluded; thus, there are no subsequent study data for these patients, including data on the long-term sequelae of COVID-19. We appreciate Dr Albulushi's interest in the interplay of RP as an autoinflammatory disease and cytokine signaling associated with COVID-19, and we concur that more data on long COVID are needed. We conclude by pointing out that RP is a chronic disease that often lasts for years, and continued collection of long-term follow up data in registries and other tools could further inform long-term management.3Klein A. Cremer P. Kontzias A. et al.US Database Study of Clinical Burden and Unmet Need in Recurrent Pericarditis.J Am Heart Assoc. 2021; 10e018950https://doi.org/10.1161/JAHA.120.018950Crossref Scopus (13) Google Scholar,4Luis S.A. Cremer P. Raisinghani A.B. et al.Rilonacept Utilization in a Steroid-Sparing Paradigm For Recurrent Pericarditis: Real World Evidence Demonstrating Increased Adoption.Journal of the American College of Cardiology. 2024; 83 (408-408) (doi:10.1016/S0735-1097(24)02398-2)Google Scholar Antonio Brucato: Institution received funding from Kiniksa Pharmaceuticals as an investigative clinical study site; unrestricted research grant from Sobi and Acarpia Farmaceutici; travel and accommodation for advisory committee from Sobi and Kiniksa Pharmaceuticals Allan L. Klein: Kiniksa Pharmaceuticals research grant, consultant, and scientific advisory board; Cardiol Therapeutics research grant and scientific advisory board; Pfizer Scientific Advisory Board Massimo Imazio: Kiniksa Pharmaceuticals scientific advisory board John F. Paolini: Employee and shareholder of Kiniksa Pharmaceuticals; inventor on patents/patent applications covering the use of rilonacept for the treatment of RP. Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110