Efficacy of anakinra in genetically associated recurrent pericarditis

Objective: IL-1 blockade marks an important step forward in the management of recurrent pericarditis that does not respond to conventional therapies. However, it is not known why a considerable percentage of patients experience recurrence during drug tapering, necessitating maintenance therapy for prolonged periods. Methods: A prospective observational cohort study was conducted at a tertiary referral center, enrolling all consecutive adult patients with recurrent pericarditis treated with anakinra. Whole exome sequencing was used to identify genetic disease-associated variants. Results: A total of 76 patients were treated with anakinra, of these 20 patients (26.3%) had genetic variants associated with pericarditis. Characteristics were similar between the groups, except for a higher frequency of fever (80.0 vs. 55.4%, p = 0.038) in the genetic group. After a mean follow-up of 30 (24–41) months, patients with genetically associated pericarditis exhibited a significantly higher percentage of recurrence (80.0% vs. 41.1%, p = 0.003), shorter time to first recurrence (p < 0.0001) and a lower possibility to discontinue anakinra (p = 0.044). Genetics remained an independent predictor of poor outcome even after multivariate analysis, conferring an approximately 4-fold increased risk of recurrence (HR 4.069, 95%CI: 2.092 to 7.913, p < 0.001) and 8-fold increased risk of failing to discontinue anakinra (HR 0.120, 95%CI: 0.027 to 0.521, p = 0.005). Conclusion: In this cohort of recurrent pericarditis treated with anakinra, approximately one in four patients showed a genetic predisposition. These patients exhibited a higher percentage of recurrence, shorter time to first recurrence, and a lower possibility to discontinue anakinra, highlighting the prognostic impact of genetic testing in patients treated with anti–IL-1 agents.