A randomised trial of prednisolone versus prednisolone and itraconazole in acute-stage allergic bronchopulmonary aspergillosis complicating asthma

Abstract

Whether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone, in reducing exacerbations, in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone-itraconazole combination versus prednisolone monotherapy in ABPA. We randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (four months) or a combination of prednisolone and itraconazole (four and six months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates and percentage decline in serum total IgE at six weeks, time to first ABPA exacerbation, and treatment-emergent adverse effects (AE). We randomised 191 subjects to receive either prednisolone (n=94) or prednisolone-itraconazole combination (n=97). The one-year exacerbation rate was 33% and 20.6% in the prednisolone and the prednisolone-itraconazole arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All the subjects experienced a composite response at 6-weeks, along with a decline in serum total IgE (mean decline, 47.6% versus 45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to AE. There was a trend towards a decline in ABPA exacerbations at 1-year with the prednisolone-itraconazole combination than prednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA.