In a patient with poorly controlled asthma on dupilumab (Dupixent) being evaluated for allergic bronchopulmonary aspergillosis who presents with an acute asthma exacerbation, should the dupilumab dose be administered today?

Should Dupilumab Be Administered During an Asthma Exacerbation in a Patient Being Evaluated for ABPA?

Yes, continue dupilumab during the asthma exacerbation while initiating appropriate acute treatment with oral corticosteroids or itraconazole for the exacerbation itself.

Rationale for Continuing Dupilumab

Dupilumab should not be discontinued during an acute asthma exacerbation or while evaluating for ABPA. The medication is designed for maintenance therapy and does not interfere with acute management 1. The FDA label explicitly states that dupilumab "should not be used to treat acute symptoms or acute exacerbations of asthma" but does not recommend discontinuation during exacerbations 1.

Key Management Principles

Treat the acute exacerbation separately while maintaining dupilumab:

• Administer oral prednisolone (0.5 mg/kg/day for 2-4 weeks, tapered over 4 months) as the most rapid-acting treatment for acute ABPA or asthma exacerbation 2
• Alternative: oral itraconazole (400 mg/day in two divided doses for 4 months) if corticosteroids are contraindicated 2
• Continue dupilumab at the scheduled dose (300 mg every 2 weeks for adults) without interruption 1

Evidence Supporting Dupilumab Continuation

Dupilumab's Role in ABPA

Dupilumab has Level III evidence for reducing asthma exacerbations and providing steroid-sparing effects in treatment-dependent ABPA 2. Recent real-world data demonstrates:

• Anti-IL-4Rα therapy (dupilumab) is superior to anti-IgE and anti-IL-5/IL-5Rα biologics for ABPA treatment, with significantly lower exacerbation rates and oral corticosteroid requirements 3
• 65% of patients with ABPA showed successful response to biologic therapy at 12 months, with significant reductions in exacerbations and maintenance corticosteroid use 4
• 8 of 10 patients achieved clinical control on dupilumab after failing other biologic classes 3

Mechanism of Benefit

Dupilumab blocks IL-4 and IL-13 pathways, which are central to ABPA pathophysiology 3. This dual blockade:

• Inhibits airway mucus generation (IL-13 pathway) 3
• Reduces B-cell differentiation into IgE-secreting cells (IL-4 pathway) 3
• Suppresses type 2 inflammatory biomarkers rapidly and sustainably 5

Acute Management Algorithm

Step 1: Differentiate the Type of Exacerbation

Determine whether this is an asthma exacerbation versus ABPA exacerbation:

• ABPA exacerbation: Sustained worsening ≥2 weeks, new infiltrates on chest imaging, AND serum total IgE increased ≥50% above baseline 2
• Asthma exacerbation: No IgE elevation, no new infiltrates, responds to standard asthma management 2
• Order: Chest radiograph, serum total IgE, and compare to baseline values 2

Step 2: Initiate Acute Treatment

For confirmed or suspected ABPA exacerbation:

• First-line: Oral prednisolone 0.5 mg/kg/day for 2-4 weeks, then taper over 4 months 2
• Alternative: Oral itraconazole 400 mg/day (divided doses with meals) for 4 months if steroids contraindicated 2
• Do NOT use high-dose inhaled corticosteroids alone as they do not achieve symptom control or reduce ABPA exacerbations 2

For asthma exacerbation without ABPA features:

• Short course of oral corticosteroids per standard asthma guidelines 2
• Optimize inhaled corticosteroid and bronchodilator therapy 2

Step 3: Continue Dupilumab Without Interruption

Administer the scheduled dupilumab dose today 1:

• Standard dosing: 300 mg subcutaneous injection every 2 weeks 1
• Can be administered in thigh, abdomen (avoiding 2 inches around navel), or upper arm 1
• Rotate injection sites with each dose 1

Important Caveats

Monitoring Considerations

While dupilumab is generally safe during exacerbations, monitor for:

• Eosinophilic conditions: Patients may present with eosinophilic pneumonia or EGPA, especially when reducing oral corticosteroids 1
• Conjunctivitis/keratitis: Occurs more frequently in atopic dermatitis patients but can occur in asthma patients; advise reporting new eye symptoms 1
• Helminth infections: Exclude or treat before continuing dupilumab if suspected 1

Drug Interactions

If combining itraconazole with corticosteroids:

• Risk of exogenous Cushing's syndrome when methylprednisolone combined with itraconazole 2
• Inhaled budesonide or fluticasone with itraconazole can also cause Cushing's syndrome 2
• Perform therapeutic drug monitoring for itraconazole (target trough ≥0.5 mg/L) 2

Corticosteroid Tapering

Do not abruptly discontinue corticosteroids when dupilumab is on board 1:

• Taper gradually under direct supervision 1
• Abrupt reduction may cause systemic withdrawal symptoms 1
• May unmask previously suppressed conditions 1

Diagnostic Workup for ABPA

While treating the exacerbation, complete ABPA diagnostic evaluation:

• Mandatory criteria: Predisposing condition (asthma), fungal sensitization (A. fumigatus-specific IgE), serum total IgE ≥500 IU/mL 2
• Plus two of: Fungal-specific IgG, peripheral blood eosinophilia, or suggestive imaging (bronchiectasis, mucus plugging) 2
• Imaging: Chest CT to assess for bronchiectasis and high-attenuation mucus plugs 2, 6

Dupilumab does not interfere with ABPA diagnostic testing and can remain on board during the evaluation period 1.