New drugs and strategies are being developed or repurposed to reduce or even eliminate the need for steroids in diseases like ABPA, where inflammation is driven by an allergic immune response to Aspergillus.

Here’s a breakdown of what’s already available and what’s on the horizon:

🧬 Biologics – the biggest game-changer

These are antibody-based therapies that target specific immune pathways, rather than suppressing the whole immune system like steroids do.

✅ Already used off-label or in trials for ABPA:

1. Omalizumab (Xolair)

  • Targets IgE (the allergy antibody that’s sky-high in ABPA)

  • Already licensed for severe allergic asthma

  • Studies show it reduces exacerbations, improves lung function, and helps taper off steroids

  • Limitations: expensive, dosing based on IgE levels and weight (difficult in patients with very high IgE)

2. Mepolizumab (Nucala)

  • Targets IL-5, which drives eosinophil activity

  • Approved for eosinophilic asthma

  • Used in some ABPA patients, especially when eosinophils remain high

  • Can help reduce steroid use and fungal exacerbations

3. Benralizumab (Fasenra)

  • Also targets IL-5 receptor – causes direct depletion of eosinophils

  • Similar benefits to mepolizumab but may act faster

  • Small studies and case reports show promise in ABPA and chronic pulmonary aspergillosis with eosinophilia

4. Dupilumab (Dupixent)

  • Blocks IL-4 and IL-13, key drivers of Th2 inflammation

  • Approved for asthma, atopic dermatitis, and nasal polyps

  • Early evidence suggests it may benefit ABPA patients, especially those with co-existing nasal polyps or eczema

  • Could be ideal for steroid-sparing in allergic fungal disease

💊 Antifungals as steroid-sparing agents

Already in use, but still being optimized:

  • Itraconazole

  • Voriconazole

  • Posaconazole

  • Isavuconazole (being explored more recently, better tolerated in some patients)

These reduce fungal burden, which helps turn down the immune overreaction—letting steroids be tapered or even avoided in some patients.

🔬 In Development or Under Investigation

🧪 Tezepelumab

  • Blocks TSLP (thymic stromal lymphopoietin) – an early signal in allergic inflammation

  • In trials for severe asthma

  • May be helpful in ABPA down the line – trials are ongoing

🧪 Anti-IL-33 and Anti-ST2 therapies

  • IL-33 is another “alarmin” involved in allergic responses

  • Still in early stages, but being watched closely for steroid-sparing potential in allergic lung diseases

🌍 Other Strategies Being Studied

  • Inhaled antifungals (e.g., inhaled voriconazole or amphotericin B) – may reduce systemic side effects

  • Vaccines against Aspergillus – still early stage

  • Mucolytics and anti-inflammatory antibiotics (e.g., azithromycin) as steroid-sparing support in some patients

🤔 What You Can Do Now

  • If you’re struggling with steroid side effects or dependency, it’s totally reasonable to ask your respiratory team:

    • “Am I a candidate for a biologic like omalizumab or mepolizumab?”

    • “Is my antifungal therapy optimized?”

    • “Would a switch to inhaled or combination therapy help reduce my steroid use?”

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