Role of Anakinra and Rilonacept in Recurrent Pericarditis
Anakinra and rilonacept are indicated as third-line therapy for corticosteroid-dependent recurrent pericarditis in patients who remain unresponsive to colchicine, after careful assessment of costs and risks, and preferably with multidisciplinary consultation. 1, 2
Treatment Algorithm for Recurrent Pericarditis
First-Line Therapy
- High-dose NSAIDs (ibuprofen 600mg every 8 hours or aspirin 500-1000mg every 6-8 hours)
- PLUS Colchicine (0.5mg twice daily for patients ≥70kg; 0.5mg once daily for patients <70kg)
- Duration: At least 3-6 months
- PLUS Exercise restriction until symptoms resolve and CRP normalizes
Second-Line Therapy
- Low-dose corticosteroids (prednisone 0.25-0.50 mg/kg/day)
- Only when contraindications to NSAIDs/colchicine exist OR incomplete response to first-line therapy
- Follow strict tapering schedule to minimize side effects:
50 mg: Reduce by 10 mg/day every 1-2 weeks
- 50-25 mg: Reduce by 5-10 mg/day every 1-2 weeks
- 25-15 mg: Reduce by 2.5 mg/day every 2-4 weeks
- <15 mg: Reduce by 1.25-2.5 mg/day every 2-6 weeks
Third-Line Therapy (IL-1 Antagonists)
- Anakinra (2 mg/kg/day up to 100 mg subcutaneously for at least 6 months, then tapered)
- OR Rilonacept (loading dose of 320 mg SC followed by 160 mg weekly)
- OR IV immunoglobulin or azathioprine
Fourth-Line Therapy
- Pericardiectomy (surgical option after thorough trial of unsuccessful medical therapy)
Evidence for IL-1 Antagonists
Rilonacept
Rilonacept is FDA-approved for recurrent pericarditis in adults and children ≥12 years 3. In the RHAPSODY trial, rilonacept demonstrated:
- 96% reduction in risk of recurrence compared to placebo
- Rapid resolution of symptoms (median 5 days to treatment response)
- 97% of patients achieved treatment response
- Only 7% of patients on rilonacept had recurrence vs. 74% on placebo
- Significantly more days with minimal/no pain compared to placebo (92% vs. 40%) 3
Anakinra
Multiple studies support anakinra's efficacy:
- In the AIRTRIP trial, anakinra reduced recurrence rate to 18.2% compared to 90% with placebo 4
- Provides rapid symptom relief (within 2-5 days) 5
- Effective in both idiopathic and non-idiopathic pericarditis 6
- Allows successful discontinuation of other medications in 84% of patients 5
Important Clinical Considerations
Patient Selection
- Candidates for IL-1 antagonists: Patients with proven infection-negative, corticosteroid-dependent recurrent pericarditis not responsive to colchicine 1, 2
- Confirm elevated inflammatory markers (CRP) before initiating therapy
- Rule out infectious causes of pericarditis before starting immunosuppressive therapy
Monitoring
- Follow CRP levels to guide treatment duration and assess response
- Monitor for symptom resolution, normalization of ECG changes, and resolution of pericardial effusion
- Schedule visits every 1-2 months until treatment completion
Side Effects
- Most common: Injection site reactions (>50% of patients) 7
- Less common: Transaminase elevation, infections (herpes zoster reported) 4
- Severe side effects are rare with discontinuation rates <4% 7
Special Populations
- Children: Anakinra or rilonacept may be preferred over corticosteroids to minimize side effects in growing children 2
- Pregnancy: Both agents should be used with caution; consult specialists
Pitfalls to Avoid
- Premature discontinuation of therapy (continue colchicine for at least 3-6 months regardless of symptom resolution)
- Inappropriate corticosteroid use (avoid as first-line therapy)
- Failure to provide gastrointestinal protection when prescribing NSAIDs
- Overlooking cardiac tamponade, which requires immediate intervention
- Not consulting with immunologists/rheumatologists when initiating IL-1 antagonist therapy
The introduction of IL-1 antagonists represents the most significant advance in recurrent pericarditis treatment in recent years 7, offering effective options for patients with refractory disease.