Pericarditis at the crossroads: Unlocking the next wave of therapies

Pericarditis is an inflammation of the pericardial sac with different aetiologies. While often self-limited, up to 30 % of cases recur or become chronic, causing significant morbidity. Traditional treatments - nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids - have important limitations, including steroid dependence, high recurrence rates, and side effects. Accordingly, new targeted immunomodulatory therapies are under investigation to improve outcomes in refractory pericarditis. This review outlines the epidemiology and burden of pericarditis, current management and its shortcomings, and the rationale for novel therapies. We then discuss emerging therapeutic agents in development (biologics and small molecules), focusing on phase II/III candidates. The central role of interleukin-1 (IL-1) and related inflammasome pathways in pericardial inflammation provides a strong rationale for these targeted treatments. Key trials of IL-1 inhibitors (anakinra, rilonacept, canakinumab, goflikicept) have demonstrated dramatic reductions in recurrence rates, validating IL-1 as a therapeutic target. Other innovative approaches - such as NLRP3 inflammasome inhibitors and a cannabinoid-based agent - offer the prospect of oral, steroid-sparing therapy. We highlight the current challenges in developing these therapies, including heterogeneous disease causes, safety concerns, and trial design issues. Overall, the therapeutic pipeline for pericarditis is robust and poised to transform management. In the coming years, integration of targeted biologics and small molecules alongside conventional anti-inflammatories may significantly improve outcomes in recurrent pericarditis, moving towards more precise and effective treatment strategies.