What is the role and dose of Omalizumab (anti-IgE antibody) in the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)?

Role and Dose of Omalizumab in ABPA

Omalizumab is recommended as a biological agent option for managing treatment-dependent Allergic Bronchopulmonary Aspergillosis (ABPA), particularly in patients who have frequent exacerbations despite conventional therapy. 1

Role of Omalizumab in ABPA

Primary Indications

• Omalizumab is indicated for treatment-dependent ABPA, where patients continue to have symptoms despite conventional therapy 1
• It serves as an alternative to continuous low-dose glucocorticoids in steroid-dependent patients 1
• Particularly beneficial in ABPA patients with elevated IgE levels, which is a hallmark of the disease 1

Clinical Benefits

• Reduces frequency of ABPA exacerbations compared to placebo 2
• Improves symptoms and lung function in patients with ABPA 1, 3
• Decreases asthma hospitalizations in ABPA patients 1
• Enables reduction in oral corticosteroid doses, minimizing steroid-related adverse effects 3, 2
• Can be used safely despite the high serum IgE levels typically seen in ABPA 2

Patient Selection

• Most appropriate for patients with:
  • Treatment-dependent ABPA (requiring ongoing therapy to maintain control) 1
  • ABPA in remission where biological agents may help prolong the remission period 1
  • ABPA complicated by severe asthma 4, 3
  • ABPA in cystic fibrosis patients (where long-term steroid use is particularly problematic) 5, 6

Dosing Considerations

While the European Respiratory Society guidelines don't specify an exact dosing regimen for omalizumab in ABPA, clinical evidence suggests the following approach:

• In the only crossover RCT conducted, a dose of 750 mg monthly was used 2
• In clinical practice, dosing is typically based on body weight and baseline serum IgE levels, similar to the dosing approach used in severe allergic asthma 3
• Treatment duration is individualized based on clinical response, but maintenance therapy may be required for prolonged periods in treatment-dependent ABPA 1

Monitoring During Treatment

• Assess treatment response after 8-12 weeks using:
  • Clinical symptoms (≥50% improvement on Likert score or Visual Analog Scale) 1
  • Chest radiographs (looking for major improvement in pulmonary opacities) 1
  • Serum total IgE levels (≥20% reduction) 1
• Continue monitoring with clinical review, serum total IgE levels, and lung function tests every 3-6 months 1
• Evaluate periodically to determine ongoing need for therapy in patients achieving remission 1

Immunological Effects

• Decreases basophil reactivity to Aspergillus fumigatus 2
• Reduces basophil FcεR1 and surface-bound IgE levels 2
• Decreases exhaled nitric oxide (FeNO) levels, indicating reduced airway inflammation 2

Comparative Efficacy and Treatment Algorithm

1. First-line options for newly diagnosed ABPA:

   • Oral glucocorticoids (prednisolone 0.5 mg/kg/day for 2-4 weeks, tapered over 4 months) 1, 7
   • Itraconazole (400 mg/day in two divided doses for 4 months) 1, 7

2. For treatment-dependent ABPA, consider:

   • Long-term itraconazole 1
   • Nebulized amphotericin B 1
   • Biological agents (omalizumab being the most studied) 1
   • Low-dose glucocorticoids (last option due to side effect profile) 1

Important Considerations and Pitfalls

• Despite high IgE levels in ABPA (often exceeding the upper limit for conventional omalizumab dosing in asthma), omalizumab has been used safely in these patients 2
• Omalizumab appears to be safe even in ABPA patients with chronic bacterial infections of the airways 4
• Early treatment with omalizumab may be more beneficial, particularly in patients with less advanced lung disease 6
• The evidence for omalizumab in ABPA is primarily based on case reports, small case series, and one small crossover RCT of 13 patients 1, 2
• Therapeutic drug monitoring is recommended when using biological agents in ABPA 1