Which is safer, AER or ZPA?

Selective COX-2 Inhibitors (ZPA) Are Safer Than Aspirin (AER) for Patients with NSAID Hypersensitivity

For patients with NSAID hypersensitivity, selective COX-2 inhibitors (ZPA) are safer than aspirin (AER) due to their significantly lower risk of adverse reactions. 1

Understanding NSAID Hypersensitivity Reactions

NSAID hypersensitivity reactions can be categorized into four main types:

1. Aspirin-Exacerbated Respiratory Disease (AERD) - Characterized by:

   • Asthma
   • Chronic rhinosinusitis with nasal polyps
   • Respiratory reactions to aspirin/NSAIDs
   • COX-1 inhibition mechanism (not IgE-mediated)

2. NSAID-Induced Urticaria and Angioedema

   • Not drug-specific
   • Cross-reactive with other NSAIDs

3. NSAID-Exacerbated Cutaneous Disease

   • Worsening of pre-existing chronic urticaria

4. Single NSAID-Induced Reactions

   • Drug-specific reactions
   • Not cross-reactive with structurally unrelated NSAIDs

Safety Comparison: ZPA vs AER

Selective COX-2 Inhibitors (ZPA)

• Extremely rare reactions in patients with AERD 1
• Can typically be taken safely by patients with any NSAID hypersensitivity phenotype 1
• Recommended as alternative analgesics when NSAIDs are needed in patients with NSAID hypersensitivity 1
• Lower risk of gastrointestinal and respiratory adverse effects

Aspirin (AER)

• High reaction rate in susceptible individuals
• In a study of 243 patients, all those with a history of severe aspirin reactions requiring hospitalization had positive oral aspirin challenges 1
• Can cause significant respiratory symptoms in AERD patients
• Requires desensitization procedure for continued use in AERD patients

Clinical Approach to NSAID Selection

For Patients with Confirmed AERD:

1. First-line option: Use selective COX-2 inhibitors (ZPA) for pain management
2. Alternative approach: Consider aspirin desensitization followed by daily aspirin therapy only if:
   • Patient requires aspirin for cardioprotection
   • Patient needs pain relief and cannot use alternatives
   • Management of nasal polyp regrowth is needed 1
   • Patient has no contraindications to aspirin therapy

For Patients with Other NSAID Hypersensitivity Phenotypes:

• Recommended: Selective COX-2 inhibitors (ZPA) 1
• Avoid: Traditional NSAIDs including aspirin (AER)

Important Considerations for Aspirin Desensitization

If aspirin therapy is absolutely necessary despite hypersensitivity:

• Must be performed in specialized centers with resuscitation capabilities
• Requires careful monitoring for adverse reactions
• Maintains tolerance only with continued daily aspirin use
• Carries risks of bleeding and other aspirin-related adverse effects

Pitfalls to Avoid

1. Diagnostic confusion: Neither skin testing nor in vitro tests are useful for diagnosing AERD - diagnosis is established by history or challenge 1

2. Unnecessary challenges: Patients with ≥2 respiratory reactions to different NSAIDs or a respiratory reaction requiring hospitalization do not need diagnostic aspirin challenges 1

3. Inappropriate drug selection: Failing to recognize that selective COX-2 inhibitors are safer alternatives for patients with NSAID hypersensitivity

4. Inadequate monitoring: Not recognizing that aspirin desensitization requires specialized facilities and expertise

In conclusion, selective COX-2 inhibitors (ZPA) provide a significantly safer alternative to aspirin (AER) for patients with NSAID hypersensitivity, particularly those with AERD, due to their minimal risk of triggering hypersensitivity reactions.