Biologic treatment of ABPA
Question:
7/12/2023
I saw a 45-year-old female with asthma and ABPA. She was diagnosed in 2018 and treated with prednisone and Voriconazole for about 12 months. Symptoms improved but then returned. CT showed tree-in-bud opacities in a pattern consistent with aspergillosis, bronchoscopy showed fungal hyphae consistent with aspergillus species, absolute eosinophil count was 1500, IgE was 6027 kU/L, A. fumigatus IgE was 35.40 kU/L, and A.fumigatus Precipitin was detected. Symptoms improved with prednisone but returned when prednisone was tapered and she was given voriconazole. Over the past several years she has been treated with prednisone and voriconazole about four times for recurrence. She is currently taking another course of prednisone and voriconazole. I am hoping to start her on a biologic as there is data to suggest that omalizumab, mepolizumab, benralizumab and dupilumab have all been effective as add on treatments for APBA. Is there one biologic that is most effective at treating ABPA than the others and are there any factors to consider when choosing one over the other for ABPA.
Answer:
Although no biologics are currently FDA-approved for the management of ABPA, case reports and case series suggest some benefits.[1,2] Overall, when compared to each other, the reduction in exacerbation rate is between 85-90% for all biologics. Reduction in steroid use is the worst for omalizumab (66%) when all the others have a 90-98% efficacy rate in reducing steroid use. Reduction of eosinophils only occur in about 50% of dupilumab users with a transient increase in eosinophils when first started, whereas the others reduce eosinophils in 70-99% of patients. [2]
Reports of Omalizumab in patients with ABPA and severe asthma showed a reduction in serum IgE, decreased exacerbation rates, and oral glucocorticoid requirements associated with symptomatic improvement [2].
Further cases reporting off-label use of Mepolizumab and Benralizumab have shown a reduction in peripheral eosinophilia and symptomatic improvement in ABPA. [1,2] A clinical trial with benralizumab was halted because of poor patient recruitment.[3]
A systematic review [4] evaluated the effectiveness of mepolizumab in ABPA in seven studies, with a total of eight patients. Subcutaneous mepolizumab 100 mg every 4 weeks was given to all patients. Eosinophil numbers dropped significantly in all patients, but only four patients had a significant reduction in total IgE levels. There were however improvements in FEV1 and radiological findings, and there was a clinical improvement in all patients with no adverse effects identified.
Another case report demonstrated dupilumab efficacy in a patient with asthma and ABPA whose symptoms were previously refractory to various treatments including maximal inhaler therapy, oral glucocorticoids, itraconazole, omalizumab, and Benralizumab [5]. A study of dupilumab for ABPA is estimated to come to completion in November of 2023. It is a Phase 2 randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of dupilumab in patients with allergic bronchopulmonary aspergillosis. [6] More information will be available for dupilumab when these results are published.
Overall, in ABPA, mepolizumab, benralizumab or dupilumab would be effective for your patient. The other considerations will be cost to the patient and the risk of side effects.
References:
1. Bernstein JS, Wechsler ME. Eosinophilic respiratory disorders and the impact of biologics. Curr Opin Pulm Med. 2023 May 1;29(3):202-208. doi: 10.1097/MCP.0000000000000951. Epub 2023 Mar 3. PMID: 36866734.
2. Moss RB. Severe Fungal Asthma: A Role for Biologics and Inhaled Antifungals. J Fungi (Basel). 2023 Jan 6;9(1):85. doi: 10.3390/jof9010085. Erratum in: J Fungi (Basel). 2023 Apr 06;9(4): PMID: 36675906; PMCID: PMC9861760.
3. https://www.clinicaltrials.gov/study/NCT04108962?cond=ABPA&rank=4
4. Lewington-Gower E, Chan L, Shah A. Review of current and future therapeutics in ABPA. Ther Adv Chronic Dis. 2021 Oct 23;12:20406223211047003. doi: 10.1177/20406223211047003. PMID: 34729149; PMCID: PMC8543630.
5. Mümmler C, Kemmerich B, Behr J, et al. Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab? Allergy Asthma Clin Immunol 2020; 16:1–4
6. https://clinicaltrials.gov/study/NCT04442269?cond=ABPA&rank=7
Carla M. Davis MD