How should patients with recurrent viral lung infections be managed while on Dupixent (dupilumab)?

Management of Patients with Recurrent Viral Lung Infections on Dupilumab

Patients with recurrent viral lung infections on Dupilumab should be managed with a combination of immunoglobulin replacement therapy and antimicrobial prophylaxis, while continuing Dupilumab therapy which may actually provide protective effects against viral infections.

Understanding Dupilumab and Viral Infections

Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation. Contrary to initial concerns, evidence suggests that Dupilumab may actually have protective effects against viral infections:

• Dupilumab treatment is associated with a reduced incidence of investigator-reported respiratory infections in patients with moderate-to-severe asthma or severe chronic rhinosinusitis with nasal polyps 1
• COVID-19 symptoms were attenuated in moderate-to-severe atopic dermatitis patients treated with Dupilumab 2
• The pathogenesis of viral infections often involves Th1/Th17 immune responses, while Dupilumab targets Th2 cytokines (IL-4 and IL-13), suggesting minimal interference with antiviral defense mechanisms 3

Management Algorithm for Recurrent Viral Lung Infections in Dupilumab Patients

Step 1: Assessment and Diagnosis

• Evaluate frequency and severity of viral infections
• Perform pulse oximetry and CT chest imaging to assess extent of lung involvement 4
• Consider infectious workup including nasal swab, sputum culture, blood culture, and PCR-based viral panels 4

Step 2: Immunoglobulin Replacement Therapy

• Initiate immunoglobulin replacement therapy for patients with recurrent viral infections 5
• Dosing recommendations:
  • Intravenous: 400-600 mg/kg every 3-4 weeks (target IgG trough level 600-800 mg/dL)
  • Subcutaneous: 100 mg/week 5
• Monitor IgG trough levels monthly during treatment 5

Step 3: Antimicrobial Management

• Consider antiviral prophylaxis with acyclovir or valacyclovir 4
• For active viral infections:
  • Document infection through clinical manifestations, physical examinations, and antimicrobial tests 4
  • Consider temporary discontinuation of Dupilumab during severe acute viral infection until clinical resolution 4
  • Resume Dupilumab once infection resolves

Step 4: Continuation of Dupilumab

• Continue Dupilumab therapy in most cases, as current evidence suggests it may actually reduce respiratory infections 1, 2
• Dupilumab has shown efficacy in reducing exacerbations in patients with COPD and type 2 inflammation 6, 7

Step 5: Monitoring and Follow-up

• Monitor frequency and severity of infections as the primary outcome measure 5
• Follow up within 2-3 days for seriously ill patients 4
• Advise patients to return if symptoms persist beyond 3 weeks 4

Special Considerations

For Severe Viral Infections

• For Grade 2 or higher respiratory symptoms (involving >25% of lung parenchyma):
  • Consider holding Dupilumab temporarily
  • Initiate prednisone 1-2 mg/kg/day with taper over 4-6 weeks
  • Consider empiric antibiotics if bacterial superinfection is suspected 4

For Patients with Common Variable Immunodeficiency (CVID)

• Manage aggressively with antimicrobials, IgG replacement, and careful attention to pulmonary status 4
• Even with adequate IgG replacement, patients may have recurrent sinusitis, otitis media, and bronchitis
• Consider addition of antibiotic prophylaxis to maintenance regimen 4

Pitfalls and Caveats

1. Do not discontinue Dupilumab unnecessarily - evidence suggests it may have protective effects against viral infections rather than increasing risk 3, 1, 2

2. Avoid live viral vaccines in patients on immunoglobulin replacement therapy 5

3. Be vigilant for bacterial superinfections - viral infections may predispose to secondary bacterial infections requiring antibiotic therapy 4

4. Monitor for corticosteroid complications if steroids are used to manage severe respiratory symptoms, as they may increase risk of gastrointestinal bleeding, peptic ulcer perforation, and impaired wound healing 4

5. Consider CMV and EBV monitoring in patients with persistent symptoms, as these viruses can reactivate in immunocompromised patients 4

By following this management approach, patients with recurrent viral lung infections on Dupilumab can experience reduced infection frequency and improved quality of life while maintaining the benefits of their Dupilumab therapy.