Pericarditis future or investigational therapies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2] Hafiz M. Ahmed, M.D.[3]
Overview
Several novel therapeutic approaches for pericarditis are under active investigation or have recently emerged. These include newer anti-IL-1 agents with extended dosing intervals, other targeted immunomodulatory therapies, biomarker-guided treatment strategies, and ongoing efforts to define optimal duration and discontinuation protocols for existing biologic therapies. The role of advanced imaging (particularly cardiac magnetic resonance) in guiding treatment decisions and predicting outcomes is also an area of active research.
Future or Investigational Therapies
These include [1]:
Goflikicept
- Goflikicept is a novel IL-1 trap (fusion protein that neutralizes both IL-1α and IL-1β) administered as 80 mg subcutaneously every 2 weeks. It has been studied in a phase 2 trial for recurrent pericarditis and demonstrated efficacy in reducing recurrences and normalizing CRP. The 2025 ACC Expert Consensus Statement includes goflikicept alongside anakinra and rilonacept as an anti-IL-1 option for recurrent pericarditis with an inflammatory phenotype, although it is not yet available in the United States. Regulatory approval and further phase 3 data are anticipated.
Optimal Duration and Discontinuation of Anti-IL-1 Therapy
- A major unresolved question is the optimal duration of anti-IL-1 therapy and how to safely discontinue these agents. Recurrence rates upon discontinuation of anakinra and rilonacept are high (approximately 50% to 75%), and long-term extension data support treatment beyond 18 months for sustained disease control. Ongoing studies are investigating strategies for gradual dose tapering, extended-interval dosing, and biomarker-guided discontinuation to reduce relapse rates.
Other Targeted Immunomodulatory Agents
- While anti-IL-1 agents have become the dominant biologic approach, other immunomodulatory pathways are being explored. Azathioprine (1 to 3 mg/kg/day) and intravenous immunoglobulin (IVIG, 400 to 500 mg/kg/day for 5 days) are currently used as alternative options for patients who fail anti-IL-1 therapy, but their evidence base is limited to observational data and small case series. Controlled trials evaluating these agents in pericarditis are needed.
Biomarker-Guided Treatment Strategies
- The distinction between inflammatory and noninflammatory phenotypes of pericarditis (based primarily on CRP levels) is a relatively new concept introduced in the 2025 ACC Expert Consensus Statement. Approximately 80% to 90% of recurrent pericarditis cases exhibit an inflammatory phenotype (CRP greater than 1 mg/dL), while 10% to 20% have a noninflammatory phenotype. Future research is needed to identify additional biomarkers beyond CRP that may help predict treatment response, guide therapy selection, and determine optimal timing for medication tapering and discontinuation.
Advanced Imaging for Treatment Guidance
- Cardiac magnetic resonance (CMR) is increasingly used to assess pericardial inflammation (late gadolinium enhancement, pericardial edema on T2-weighted sequences) and may help distinguish active inflammation from chronic fibrosis. The role of CMR in guiding treatment decisions, such as determining when to initiate or discontinue anti-inflammatory therapy, or when to proceed with pericardiectomy, is an active area of investigation. Similarly, the use of CT and PET imaging to quantify pericardial inflammation and predict treatment response is being explored.
Intrapericardial Therapies
- Intrapericardial instillation of corticosteroids (such as triamcinolone) has been described in small studies as a method to deliver high local anti-inflammatory concentrations while minimizing systemic side effects. This approach remains investigational and is not widely adopted, but may be considered in select refractory cases at experienced centers.
Genetic and Autoinflammatory Mechanisms
- Emerging evidence suggests that some patients with recurrent pericarditis may harbor genetic variants in autoinflammatory pathways (such as mutations associated with familial Mediterranean fever or other periodic fever syndromes). Genetic testing and characterization of these pathways may lead to more personalized treatment approaches in the future.
References
- ↑ Wang, T. K. M., Klein, A. L., Cremer, P. C., Imazio, M., Kohnstamm, S., Luis, S. A., Mardigyan, V., Mukherjee, M., Ordovas, K., Vakamudi, S., & Wohlford, G. F. (2025). 2025 concise clinical guidance: An ACC expert consensus statement on the diagnosis and management of pericarditis: A report of the American college of cardiology solution set oversight committee. Journal of the American College of Cardiology, 86(25), 2691–2719. https://doi.org/10.1016/j.jacc.2025.05.023