Recurrent pericarditis is a chronic, often debilitating, autoinflammatory condition involving repeated inflammation of the pericardium, the sac-like tissue surrounding the heart. Standard first-line treatments typically involve a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. For many, this is sufficient to resolve symptoms and prevent relapse. However, a significant subset of patients either fails to respond to these therapies or develops dependence on corticosteroids, which are often used as a second-line treatment but are associated with a higher risk of recurrence and significant side effects.
For these challenging, refractory cases, more advanced therapeutic options are needed. The discovery that the inflammatory process in recurrent pericarditis is often driven by the interleukin-1 (IL-1) pathway opened the door for new targeted therapies, such as the IL-1 receptor antagonist, anakinra.
The Role of Anakinra in Refractory Pericarditis
Anakinra (Kineret®) is a recombinant version of the naturally occurring human interleukin-1 receptor antagonist (IL-1Ra). By competitively binding to IL-1 receptors, it effectively blocks the activity of both IL-1α and IL-1β, which are key pro-inflammatory cytokines in the autoinflammatory process of recurrent pericarditis.
The use of anakinra is particularly beneficial for patients who are considered to have a highly inflammatory phenotype, characterized by elevated C-reactive protein (CRP) levels and multiple recurrences that are unresponsive to conventional treatment. Its targeted mechanism offers a way to interrupt the inflammatory cascade without the broad, long-term side effects associated with corticosteroids.
Clinical Evidence: The AIRTRIP and IRAP Studies
The efficacy and safety of anakinra for recurrent pericarditis have been supported by several studies, including the Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) trial and the International Registry of Anakinra for Pericarditis (IRAP).
- The AIRTRIP Trial (2016): This small but significant double-blind, placebo-controlled, randomized withdrawal trial demonstrated anakinra's effectiveness. Among patients with colchicine-resistant, corticosteroid-dependent recurrent pericarditis, the use of anakinra led to a significantly lower risk of recurrence (18.2%) compared to the placebo group (90%) over 14 months.
- The IRAP Registry (2020): A larger, multicenter observational study confirmed anakinra's positive effects in a real-world setting. In a cohort of 224 patients with refractory recurrent pericarditis, anakinra therapy significantly reduced the recurrence rate and led to a marked decrease in emergency department visits and hospitalizations. The study also showed a considerable reduction in the need for corticosteroid use.
Anakinra vs. Conventional and Alternative Therapies
For patients with recurrent pericarditis, the choice of therapy depends on the severity of the disease and response to initial treatments. Here is a comparison of common therapeutic options:
| Feature | NSAIDs/Aspirin | Colchicine | Anakinra | Rilonacept | Corticosteroids |
|---|---|---|---|---|---|
| Mechanism | Anti-inflammatory, non-targeted | Anti-inflammatory, inhibits inflammasome | IL-1 receptor antagonist | Soluble IL-1 trap | Broad immunosuppression |
| Indication | First-line therapy | First-line therapy, adjuvant | Third-line, refractory cases | Refractory cases (FDA-approved) | Second-line, bridge therapy |
| Efficacy in Recurrent Pericarditis | Modest, high recurrence risk | High, reduces recurrence risk | High, reduces recurrences significantly | High, reduces recurrences significantly | High short-term, high long-term recurrence risk |
| Onset of Action | Hours to days | Days to weeks | Rapid (days) | Rapid (days) | Rapid (hours to days) |
| Common Side Effects | GI upset, renal impairment | Diarrhea, abdominal pain | Injection site reactions, flu-like symptoms | Injection site reactions, URI, neutropenia | Weight gain, hyperglycemia, osteoporosis |
| FDA Approval for Recurrent Pericarditis | No | No (used off-label) | No (used off-label) | Yes | No (used off-label) |
| Primary Goal | Resolve symptoms, reduce inflammation | Reduce recurrences | Reduce recurrences, enable steroid withdrawal | Prevent recurrence | Control severe inflammation quickly |
Administering Anakinra: Considerations
In clinical practice, anakinra is typically administered as a subcutaneous injection. The specific administration schedule and duration of treatment are determined by a healthcare professional based on the individual patient's condition. The treatment is usually continued for a period of months while other medications like corticosteroids are tapered and discontinued. Slow tapering of anakinra itself may then be attempted, although patients should be monitored closely for relapse. Continued use might be necessary for long-term remission in some cases. Combining anakinra with colchicine may offer additional benefits in preventing recurrence.
Safety Profile and Potential Side Effects
Anakinra is generally considered safe and well-tolerated, especially when compared to the long-term use of corticosteroids. The most common side effect is a transient injection site reaction, which can involve redness, swelling, or pain. These reactions often subside after the first few weeks of therapy and can be managed with topical or oral medications.
Serious side effects are less common but include an increased risk of serious infections, especially in patients with a history of tuberculosis. Therefore, patients should be screened for latent infections, particularly tuberculosis and hepatitis B, before starting treatment. Other potential side effects include headache, nausea, and changes in blood cell counts, such as neutropenia.
Conclusion: A Targeted Treatment for a Challenging Condition
For patients with recurrent, refractory pericarditis, anakinra has emerged as a crucial treatment option. As an IL-1 receptor antagonist, it directly addresses the underlying autoinflammatory mechanism driving the disease, providing a highly effective alternative to corticosteroids. Clinical evidence from trials like AIRTRIP and registries like IRAP confirms its ability to significantly reduce disease recurrence and facilitate the withdrawal of conventional, often problematic, steroid therapy. While not FDA-approved for pericarditis (unlike its counterpart rilonacept), anakinra's off-label use is well-supported by current data for refractory cases. Its targeted action, rapid onset, and generally favorable safety profile make it an invaluable tool for cardiologists and rheumatologists managing this challenging condition. Ongoing research will continue to refine optimal treatment strategies and tapering protocols to help patients achieve and maintain long-term remission.
For more information on the role of anti-inflammatory agents in pericarditis, see the article on the topic published in European Heart Journal.
