What is the treatment for Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)?

Treatment for Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

Canakinumab is the first-line treatment for TRAPS, administered at 2-4 mg/kg every 4 weeks for pediatric patients or 150-300 mg every 4 weeks for adults weighing over 40 kg. 1

First-Line Treatment Options

IL-1 Inhibitors

• Canakinumab (First-line)

  • FDA and EMA approved for TRAPS with level 1B evidence 1
  • Pediatric dosage: 2-4 mg/kg subcutaneously every 4 weeks
  • Adult dosage (>40 kg): 150-300 mg subcutaneously every 4 weeks
  • Demonstrated efficacy in randomized controlled trials 2

• Anakinra (Alternative first-line)

  • Dosage: 1-2 mg/kg/day 1
  • Level 4C evidence
  • Was the first IL-1 blocker successfully used in TRAPS in small series and observational registries 1

Second-Line Treatment Options

TNF Inhibitors and Glucocorticoids

• Short-term glucocorticoids

  • May be effective for individual patients during flares
  • Responses often wane over time
  • Requires monitoring for increased disease activity 1
  • Extended use limited by adverse effects

• Etanercept

  • May be effective in individual patients
  • Responses often diminish over time
  • Requires close monitoring for disease activity 1
  • Note: Other TNF inhibitors like infliximab have shown treatment failure in some cases 3

Treatment Algorithm

1. Initial Assessment

   • Confirm TRAPS diagnosis with genetic testing (TNFRSF1A mutations)
   • Evaluate disease severity and pattern (episodic vs. chronic)
   • Check inflammatory markers (CRP, ESR, SAA)

2. First-line Treatment

   • Start canakinumab at appropriate weight-based dosing
   • For patients with milder disease or episodic flares, consider on-demand treatment
   • If canakinumab is unavailable, use anakinra

3. Treatment Monitoring

   • Assess response at 15 days (complete response defined as PGA <2 and normalized CRP or ≥70% reduction) 2
   • Monitor inflammatory markers every 4-8 weeks
   • Screen for proteinuria every 6 months to detect amyloidosis 1

4. Dose Adjustment

   • If inadequate response, consider dose escalation:
     • For canakinumab: increase to 300 mg (or 4 mg/kg) every 4 weeks 2
     • For anakinra: increase dose as needed

5. Alternative Approaches

   • If IL-1 blockade is ineffective, consider TNF inhibitors 1
   • For acute flares only, short-term glucocorticoids may be used

Special Considerations

Disease Monitoring

• Regular assessment of inflammatory markers (CRP, ESR, SAA)
• Monitor for development of AA amyloidosis, particularly in patients with:
  • Longstanding uncontrolled disease
  • Positive family history of amyloidosis
  • Structural TNFRSF1A mutations 1

Transition from Pediatric to Adult Care

• Implement developmentally appropriate measures
• Foster self-management skills
• Address reproductive health issues
• Ensure timely transition to adult medical care 1

Vaccination

• Patients should receive pneumococcal vaccination
• Preferably administer vaccines before starting treatment, though acceptable during treatment 1

Pregnancy

• Benefit-risk discussion should occur before conception
• Current evidence supports anakinra over other IL-1 inhibitors during pregnancy 1

Common Pitfalls and Caveats

1. Misdiagnosis: Patients with non-pathogenic TNFRSF1A variants (D41E, I57S, P75L, R121Q, N145S) do not have true TRAPS but may still have autoinflammation requiring treatment 1

2. Inadequate Monitoring: Failure to monitor for amyloidosis can lead to renal failure; regular proteinuria screening is essential 1

3. Treatment Resistance: Some patients may develop resistance to initial therapy, requiring dose escalation or switching between biologics

4. Infection Risk: Monitor for respiratory tract infections with Streptococcus pneumoniae and skin infections due to Staphylococcus 1

5. Disease Progression: TRAPS may progress from episodic fever to chronic inflammation, increasing amyloidosis risk and necessitating long-term biological therapy 1

The treatment approach should focus on controlling systemic inflammation to prevent long-term complications, particularly amyloidosis, which significantly impacts morbidity and mortality in TRAPS patients.