What is the role of biologics, such as omalizumab (anti-IgE antibody), in the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)?

Role of Biologics in ABPA

Biologics are recommended as effective treatment options for treatment-dependent ABPA, with omalizumab being the most extensively studied agent, though emerging evidence suggests anti-IL-4Rα therapy (dupilumab) may be superior to other biologic classes. 1, 2

Primary Indications for Biologics in ABPA

Biologics should be considered in the following clinical scenarios:

• Treatment-dependent ABPA (10-25% of patients) who require ongoing therapy to maintain disease control despite conventional treatment with oral glucocorticoids and/or itraconazole 1, 3
• Patients with frequent exacerbations (≥2 in the last 1-2 years) despite optimal conventional therapy 4
• Steroid-dependent patients where biologics serve as an alternative to continuous low-dose glucocorticoids, which should be the last resort 1, 3
• Maintenance therapy during remission to prolong the remission period, particularly in those with prior treatment-dependent disease 1, 4

Biologic Agent Selection and Comparative Efficacy

Omalizumab (Anti-IgE)

• Most extensively studied biologic in ABPA with the strongest evidence base 1, 3
• Particularly rational choice given ABPA's hallmark elevated IgE levels 1, 3
• The only RCT evidence comes from a small crossover trial (n=13) showing reduced exacerbations and decreased basophil reactivity to Aspergillus fumigatus 1, 5
• Real-world data demonstrates improvement in symptoms, reduction in exacerbations and asthma hospitalizations, improved lung function, and reduced oral steroid doses 1, 3, 6
• Safe even in patients with very high IgE levels (mean 2314 IU/mL in trials) and those with chronic bacterial infections (Pseudomonas aeruginosa, nontuberculous mycobacteria) 6, 5
• Reduces basophil sensitivity to A. fumigatus and surface-bound IgE/FcεR1 levels 5

Dupilumab (Anti-IL-4Rα)

• Emerging as potentially the most effective biologic class for ABPA based on recent comparative data 2
• A 2025 retrospective analysis found anti-IL-4Rα therapy associated with significantly lower exacerbations and oral corticosteroid use compared to anti-IgE or anti-IL-5/IL-5Rα therapies 2
• In patients who failed anti-IgE and/or anti-IL-5/IL-5Rα therapies, 8 of 10 achieved clinical control when switched to dupilumab 2
• Mechanistic advantage: blocks both IL-4 (reducing IgE production) and IL-13 (reducing airway mucus generation), addressing two key ABPA pathophysiologic mechanisms 2
• Meta-analysis confirms significant reductions in exacerbation rates, oral corticosteroid use, and total IgE levels 7

Mepolizumab and Benralizumab (Anti-IL-5/IL-5Rα)

• Used in ABPA patients based on case reports and small series 1
• Meta-analysis shows mepolizumab significantly reduces exacerbations, oral corticosteroids, and total IgE levels 7
• Benralizumab shows similar trends but without statistical significance in pooled analyses 7
• Less effective than dupilumab in head-to-head comparisons 2

Tezepelumab (Anti-TSLP)

• Limited evidence with only weak support for efficacy in ABPA 1, 7

Treatment Algorithm

For newly diagnosed acute ABPA:

• First-line: Oral prednisolone (0.5 mg/kg/day for 2-4 weeks, tapered over 4 months) OR oral itraconazole (400 mg/day for 4 months) 4
• Biologics are NOT first-line therapy 4

For treatment-dependent ABPA:

1. Consider long-term itraconazole, nebulized amphotericin B, or biological agents (Level of Consensus: 71% for biologics) 1
2. Preferred biologic choice based on current evidence: Dupilumab (anti-IL-4Rα) appears most effective 2
3. Alternative if dupilumab unavailable or contraindicated: Omalizumab (most studied, proven safe even with very high IgE) 3, 6, 5
4. Third-line biologics: Mepolizumab or benralizumab 7
5. Continuous low-dose glucocorticoids should be the last option 1

Monitoring and Response Assessment

Initial assessment (8-12 weeks):

• Clinical symptoms improvement 1, 3, 4
• Serum total IgE reduction ≥35% from baseline (or ≥20% for good response) 4
• Chest radiograph improvement 1, 3, 4

Ongoing monitoring:

• Clinical review, serum total IgE levels, and lung function tests every 3-6 months for the first year, then every 6-12 months 1, 3

Important Clinical Considerations and Pitfalls

Treatment duration:

• No established fixed duration for biologic therapy in ABPA 4
• Treatment is individualized based on clinical response, but maintenance therapy may be required for prolonged periods in treatment-dependent disease 3
• Periodic assessments needed to determine ongoing need for therapy 1

Predictors of response:

• Mucus plugging on imaging is associated with non-response to biologic therapy 8
• Real-world data shows 65% of patients have successful response at 12 months with ≥50% reduction in oral corticosteroid use 8
• 35% of patients may fail or require biologic change 8

Safety considerations:

• Biologics are generally safe with minimal serious adverse effects 7
• Omalizumab is safe even in patients with chronic bacterial infections (P. aeruginosa, NTM) 6
• No worsening of respiratory infections observed during biologic treatment 6

Dual benefit:

• Biologics should also be considered for maintenance therapy of underlying severe asthma, which commonly coexists with ABPA 1