Would a history of IgG4-related sclerosis disease preclude the use of Dupixent (dupilumab) for treating chronic sinusitis and nasal polyps?

Dupilumab for Chronic Sinusitis with Nasal Polyps in a Patient with IgG4-Related Sclerosis Disease

A history of IgG4-related sclerosis disease does not preclude the use of dupilumab for treating chronic sinusitis with nasal polyps, and dupilumab remains an appropriate treatment option for this patient.

Rationale for Using Dupilumab in This Patient

Dupilumab is a fully human monoclonal antibody that binds to the interleukin-4 receptor α (IL-4Rα) subunit, inhibiting both IL-4 and IL-13 signaling pathways and blocking key drivers of type 2 inflammation 1. The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2020) strongly supports the use of dupilumab for chronic rhinosinusitis with nasal polyps (CRSwNP) in patients with inadequately controlled disease 2.

Efficacy of Dupilumab in CRSwNP:

• Significantly improves multiple outcomes compared to placebo:
  • SNOT-22 quality of life scores
  • Rhinosinusitis disease severity (VAS)
  • Nasal congestion/obstruction
  • Sense of smell (UPSIT score)
  • Nasal polyp score
  • Sinus opacification on CT (Lund-Mackay score)
  • Lung function in patients with comorbid asthma 2, 1

IgG4-Related Disease and CRSwNP Considerations

While IgG4-related disease can involve nasal manifestations with chronic rhinosinusitis, there is no evidence in the current literature suggesting that dupilumab is contraindicated in patients with IgG4-related sclerosis disease 3. In fact:

1. IgG4-related CRS is a distinct clinical entity associated with high serum IgG4 levels, for which steroid therapy is typically effective 3.

2. Dupilumab works by inhibiting IL-4 and IL-13 signaling pathways, which are key drivers of type 2 inflammation in CRSwNP, rather than directly affecting IgG4 production 1, 4.

3. The mechanism of action of dupilumab does not suggest any negative interaction with the pathophysiology of IgG4-related disease.

Treatment Approach for This Patient

1. Initial Assessment:

   • Confirm the presence of nasal polyps, as recommended by clinical practice guidelines 2
   • Evaluate the severity of symptoms using validated measures (SNOT-22, VAS)
   • Assess for comorbid conditions like asthma, which may strengthen the indication for dupilumab 1

2. Treatment Protocol:

   • Standard dosing: 300 mg subcutaneously every 2 weeks 1
   • Continue intranasal corticosteroids during dupilumab treatment 2
   • Monitor response using validated outcome measures (nasal polyp score, SNOT-22, VAS, smell testing) 1

3. Expected Benefits:

   • Reduction in nasal polyp size
   • Improvement in nasal congestion and other symptoms
   • Enhanced quality of life
   • Reduced need for systemic corticosteroids and nasal polyp surgery 4, 5

Monitoring Considerations

• Regular assessment of treatment response using validated measures
• Monitoring for common adverse effects:
  • Injection site reactions
  • Nasopharyngitis
  • Headache 1
• Particular attention to any changes in IgG4-related disease manifestations, though no specific interactions are expected

Patient Preference Consideration

Recent evidence shows that among patients who had previous surgical intervention for nasal polyps, 91.5% preferred therapy with dupilumab to repeated surgery 6. This preference was even stronger (100%) in patients with comorbid NSAID-Exacerbated Respiratory Disease (N-ERD) and very high (96%) in those with comorbid asthma 6.

Conclusion

Based on current evidence, dupilumab is an appropriate and potentially beneficial treatment option for this patient with chronic sinusitis and nasal polyps, despite her history of IgG4-related sclerosis disease. The mechanism of action of dupilumab targeting IL-4 and IL-13 pathways does not suggest any negative interaction with IgG4-related disease pathophysiology, and the benefits of improved symptom control and quality of life likely outweigh any theoretical concerns.