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European Respiratory Society, European Respiratory Journal, 6(59), p. 2102218, 2021

DOI: 10.1183/13993003.02218-2021

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Nebulised liposomal-amphotericin-B as maintenance therapy in ABPA: a randomised, multicentre, trial

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

BackgroundIn allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.MethodsWe performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters.ResultsAmong 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference −0.6%, 95% CI −16.8– +15.6%; OR 0.98, 95% CI 0.50–1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168–476 days) versus 177 days (64–288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group.ConclusionsIn ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.