What is the best treatment approach for a patient with Cryopyrin-Associated Periodic Syndrome (CAPS) on rilonacept who is experiencing recurrent pericarditis?

Treatment of Recurrent Pericarditis in CAPS Patients on Rilonacept

Continue rilonacept therapy and optimize the dose to 160 mg weekly (or 2.2 mg/kg for patients 12-17 years), as rilonacept is FDA-approved for both CAPS and recurrent pericarditis, making it the ideal single agent to address both conditions simultaneously. 1

Rationale for Continuing Rilonacept

• Rilonacept is specifically FDA-approved for treating both CAPS and recurrent pericarditis, making it uniquely suited for this dual-indication scenario 1
• The drug targets IL-1α and IL-1β, which are central mediators in both CAPS pathophysiology and recurrent pericarditis inflammation 2, 3
• In the phase 3 RHAPSODY trial, rilonacept demonstrated a 96% reduction in pericarditis recurrence risk (hazard ratio 0.04; 95% CI, 0.01-0.18; P<0.001) compared to placebo 3
• Median time to pain resolution was 5 days and CRP normalization was 7 days in patients with active recurrent pericarditis 3

Dosing Verification and Optimization

For adults with CAPS already on rilonacept:

• Verify current dose is 160 mg subcutaneously once weekly (following a 320 mg loading dose if not previously given) 1
• For patients 12-17 years: dose should be 2.2 mg/kg weekly (maximum 160 mg), following a 4.4 mg/kg loading dose (maximum 320 mg) 1

If recurrent pericarditis develops despite appropriate rilonacept dosing:

• First, confirm medication adherence and proper administration technique 1
• Check that the patient is not missing doses - if a dose is missed, it should be administered within 7 days 1

Adjunctive Therapy Considerations

If pericarditis symptoms persist despite optimized rilonacept:

Add first-line conventional therapy as bridge treatment:

• Aspirin 500-1000 mg every 6-8 hours OR ibuprofen 600 mg every 8 hours with gastroprotection 4
• Add colchicine 0.5 mg twice daily (≥70 kg) or 0.5 mg once daily (<70 kg) for at least 6 months 4
• Monitor CRP levels to guide treatment duration and assess response 4

Avoid corticosteroids as first-line therapy because they increase recurrence rates up to 50% and promote chronicity 4

Monitoring Strategy

Track the following parameters:

• CRP levels regularly to assess inflammatory control 4, 3
• Pericarditis pain scores using a numeric rating scale 2, 3
• Echocardiography to monitor for effusion and assess for tamponade risk 4
• ECG changes to document resolution of pericarditis 4

Exercise restriction:

• Restrict exercise until symptoms resolve and CRP, ECG, and echocardiogram normalize 4
• For athletes, maintain restriction for at least 3 months after normalization 4

Long-Term Management

Duration of rilonacept therapy:

• Long-term extension data shows sustained efficacy up to 96 weeks in CAPS patients 5
• In recurrent pericarditis, the RHAPSODY long-term extension demonstrated continued response with median treatment duration of 22 months 6
• Patients continuing rilonacept had only 3% recurrence rate versus 75% recurrence in those who suspended treatment (98% risk reduction; hazard ratio 0.02; P<0.0001) 6
• Treatment suspension should be avoided as 75% of patients experienced recurrence with median time of 11.8 weeks after stopping 6

Safety Monitoring

Common adverse events to monitor:

• Injection-site reactions (most common) 2, 3
• Upper respiratory tract infections 2, 3, 5
• Screen for active infections before continuing therapy - rilonacept should not be initiated during active infection 7
• Screen for tuberculosis exposure or untreated TB before continuing 7

Critical Pitfalls to Avoid

Do not add high-dose corticosteroids (>0.5 mg/kg/day prednisone) as they dramatically increase recurrence risk and promote chronicity 4

Do not discontinue rilonacept prematurely - the data clearly shows that stopping therapy leads to rapid recurrence in the majority of patients 6

Do not undertaper conventional therapies too quickly if added - taper only when patient is asymptomatic and CRP is normalized, decreasing one drug class at a time 4

Do not ignore inadequate initial treatment - this is the most common cause of recurrence in general pericarditis populations 4