What is the initial treatment for a patient suspected of having cryopyrin-associated periodic syndrome (CAPS)?

Initial Treatment for Suspected Cryopyrin-Associated Periodic Syndrome (CAPS)

Begin IL-1 blocking therapy immediately upon clinical suspicion of CAPS, even before genetic confirmation, as early treatment prevents irreversible organ damage including hearing loss, neurologic impairment, and amyloidosis. 1

First-Line Treatment Options

For Adults and Pediatric Patients ≥12 Years

Canakinumab is the preferred initial agent due to its superior convenience (every 8 weeks dosing), excellent efficacy across all CAPS phenotypes, and strong evidence base 1, 2:

• Adults and children >40 kg: 150 mg subcutaneously every 8 weeks 1
• Pediatric patients ≤40 kg: 2 mg/kg subcutaneously every 8 weeks 1
• Expect clinical response within 24-72 hours 2, 3
• 79 of 85 patients (93%) achieved complete response within 8 days in the largest CAPS cohort studied 2

Alternative: Anakinra if canakinumab is unavailable or for patients requiring more flexible dosing 1:

• Dosing: 1-8 mg/kg/day subcutaneously (typically 100 mg daily in adults) 1
• Advantage: Daily dosing allows rapid titration
• Disadvantage: Daily injections reduce compliance, particularly problematic in pediatric patients

Alternative: Rilonacept (FDA-approved for CAPS) 1, 4:

• Loading dose: 320 mg (two 160 mg injections same day, different sites) 4
• Maintenance: 160 mg subcutaneously weekly 4
• Pediatric (12-17 years): Loading 4.4 mg/kg (max 320 mg), maintenance 2.2 mg/kg weekly (max 160 mg) 4

Disease Severity Determines Dosing Requirements

Patients with severe CAPS phenotypes (NOMID/CINCA) require more aggressive dosing than those with milder disease (FCAS, MWS) 1, 5:

• NOMID/CINCA patients: Frequently need dose escalation to 4-8 mg/kg every 4 weeks for canakinumab, or higher daily anakinra doses (up to 8 mg/kg/day) 1
• MWS patients: May require more frequent canakinumab dosing (every 4 weeks instead of 8 weeks) despite FDA approval at 8-week intervals 1
• FCAS patients: Usually respond well to standard dosing 1
• Younger children consistently require higher weight-based doses and more frequent administration regardless of phenotype 5

Do Not Wait for Genetic Confirmation

Initiate treatment based on clinical presentation (urticaria-like rash, fever, systemic inflammation, elevated acute phase reactants) while awaiting NLRP3 genetic testing 1:

• Genetic confirmation can take weeks
• Delayed treatment allows progression of irreversible complications (hearing loss, cognitive impairment, amyloidosis) 1
• Negative genetic testing does not exclude CAPS—somatic mosaicism may require deep sequencing not captured by standard NGS 1

Monitoring Treatment Response

Assess response at 24-72 hours and adjust dosing if incomplete response 2, 3:

• Complete response criteria: Resolution of fever, rash, and symptoms PLUS normalization of CRP/SAA (<10 mg/L) 1
• Monitor at each visit: Fever, urticaria-like rash, headaches, musculoskeletal symptoms, conjunctivitis, ESR, CRP, SAA (if available), S100 proteins 1
• If CRP/SAA remain elevated or symptoms persist: Increase dose or frequency rather than switching agents 1, 5
• 90% of patients maintained remission without relapse when adequately dosed 2

Critical Baseline Assessments Before Starting Treatment

Perform these evaluations immediately to establish baseline and guide monitoring 1:

• Audiology: Formal audiometry (progressive sensorineural hearing loss occurs in moderate-severe CAPS) 1
• Ophthalmology: Slit lamp examination and retinal evaluation (conjunctivitis, uveitis, papilledema from increased intracranial pressure) 1
• Neurology assessment if severe phenotype: MRI brain (chronic aseptic meningitis, increased intracranial pressure in NOMID/CINCA) 1
• Urinalysis: Screen for proteinuria (AA amyloidosis risk) 1
• Inflammatory markers: CRP, ESR, SAA, S100 proteins (if available) 1

Common Pitfalls and How to Avoid Them

Do not underdose pediatric patients or those with severe phenotypes 1, 5:

• Children and NOMID/CINCA patients consistently require higher weight-based doses
• 24.1% of patients required dose escalation, predominantly children and severe CAPS 2
• Phenotype severity, not age alone, drives dosing requirements 5

Do not delay treatment for genetic confirmation 1:

• Clinical diagnosis is sufficient to initiate therapy
• Irreversible damage (hearing loss, cognitive impairment) progresses during untreated periods

Do not use glucocorticoids as monotherapy 1:

• IL-1 blockade controls inflammation without glucocorticoid toxicity
• Glucocorticoids do not prevent long-term complications

Avoid PPSV-23 pneumococcal vaccine in CAPS patients 1:

• 80% of CAPS patients experienced severe vaccine reactions (fever, local reactions, disease flares) after PPSV-23 1
• Use PCV10/13 instead, which showed 0% reaction rate 1
• This is a critical safety consideration unique to CAPS

Monitor for infections but do not withhold treatment 1, 2:

• Infections (predominantly mild-moderate respiratory) occurred in 65.7% of patients but were responsive to standard treatment 2
• Serious infections occurred in only 10.8% of patients 2
• Benefits of preventing CAPS complications far outweigh infection risk

Transition from Other IL-1 Blockers

If switching from anakinra to canakinumab 1:

• Discontinue anakinra
• Begin canakinumab at the time of the next scheduled anakinra dose
• No washout period required