What is the comparison between rilonacept (Interleukin-1 trap) and canakinumab (Ilaris) (anti-Interleukin-1 beta antibody) for a patient with Cryopyrin-Associated Periodic Syndrome (CAPS) and recurrent pericarditis?

Comparison of Rilonacept vs Canakinumab (Ilaris)

For CAPS (Cryopyrin-Associated Periodic Syndromes)

Both rilonacept and canakinumab are equally effective first-line IL-1 blocking agents for CAPS with equivalent Level 1B evidence, but canakinumab offers less frequent dosing (every 8 weeks vs weekly) and has broader regulatory approval (FDA + EMA vs FDA only for rilonacept). 1

Regulatory Status & Evidence Quality

• Canakinumab: FDA and EMA approved for CAPS (FCAS and MWS) with Level 1B evidence 1
• Rilonacept: FDA approved only (not EMA approved) for CAPS with Level 1B evidence 1
• Both agents have equivalent strength of evidence from randomized controlled trials 1

Dosing Regimens

Canakinumab dosing 1:

• Pediatric: 2-8 mg/kg subcutaneously every 8 weeks
• Adult (>40 kg): 150-600 mg subcutaneously every 8 weeks
• Key advantage: Dosing interval of 8 weeks

Rilonacept dosing 1:

• Pediatric: Loading dose 4.4 mg/kg weekly, maintenance 2.2 mg/kg weekly
• Adult: Loading dose 320 mg weekly, maintenance 160 mg weekly
• Key disadvantage: Requires weekly subcutaneous injections

Clinical Efficacy

Canakinumab 2, 3:

• Achieves complete clinical response in 97% of CAPS patients within 8 weeks 3
• 71% of responses occur within 8 days 3
• Normalizes inflammatory markers (CRP, SAA) within days 2, 3
• Sustained disease control maintained over 2 years 3

Rilonacept 4, 5:

• Reduces composite symptom scores by 84% vs 13% with placebo 5
• Normalizes SAA levels (reducing amyloidosis risk) 5
• Sustained efficacy demonstrated up to 96 weeks 4
• Mean symptom flare days reduced from 34.8% to 2.9% of days 4

Safety & Tolerability Profile

Canakinumab 3, 6:

• Generally well tolerated with mild-to-moderate infections as predominant adverse events 3
• Significantly fewer injection site reactions compared to daily IL-1 blockers 6
• Longer plasma half-life provides sustained IL-1β suppression 6

Rilonacept 4, 5:

• Most common adverse events: injection site reactions and upper respiratory infections 4, 5
• Generally favorable safety profile in both adults and children 4, 5
• Injection site reactions more common than with canakinumab due to weekly administration 4

Practical Considerations

Choose canakinumab when 1, 3:

• Patient compliance with weekly injections is a concern
• Minimizing injection site reactions is a priority
• Treatment is needed in Europe (EMA approval)
• Longer dosing intervals improve quality of life

Choose rilonacept when 1, 4:

• Canakinumab is unavailable or cost-prohibitive
• Patient is in the United States with FDA-approved access
• More frequent dose adjustments may be needed initially

Important Caveats

• For severe CAPS (NOMID/CINCA): Anakinra has stronger evidence (Level 2A) and is preferred over both agents 1
• Some MWS patients may require more frequent canakinumab dosing than the standard 8-week interval 1
• Both agents require continuous administration for sustained disease control 1
• Treat-to-target strategies using clinical symptoms and CRP normalization (<5-10 mg/L) should guide dose adjustments 1

For Recurrent Pericarditis

Neither rilonacept nor canakinumab is first-line therapy for idiopathic recurrent pericarditis—aspirin/NSAIDs plus colchicine should be used first. 1, 7

Treatment Algorithm for Recurrent Pericarditis

First-line 1, 7:

• Aspirin 500-1000 mg every 6-8 hours OR ibuprofen 600 mg every 8 hours
• PLUS colchicine 0.5 mg twice daily (≥70 kg) or once daily (<70 kg) for at least 6 months

Second-line 1:

• Low-dose corticosteroids (prednisone 0.2-0.5 mg/kg/day) after failure of first-line and exclusion of infection

Third-line 1, 7:

• Anakinra, IVIG, or azathioprine for corticosteroid-dependent cases not responsive to colchicine
• Rilonacept may be considered for patients who cannot tolerate conventional therapy 8

Key Distinction: CAPS with Pericarditis vs Idiopathic Recurrent Pericarditis

• If pericarditis occurs in the context of CAPS, IL-1 blockers (canakinumab or rilonacept) are appropriate first-line therapy as part of CAPS management 1
• If pericarditis is idiopathic/non-CAPS, follow the standard pericarditis algorithm with NSAIDs/colchicine first 1, 7