P080 Comparison of efficacy of innovator molecule of itraconazole with generic forms of itraconazole in treatment naïve subjects with chronic pulmonary aspergillosis

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectiveItraconazole capsule has a variable and unpredictable bioavailability. Whether generic brands of itraconazole are as effective as the innovator molecule in the treatment of subjects with chronic pulmonary aspergillosis (CPA) is unclear. We compared the proportion of subjects who achieved therapeutic drug levels with the generic and the innovator itraconazole at 2 weeks after treatment initiation.MethodsIn this retrospective study, we compared the proportion of subjects with CPA achieving therapeutic drug levels (≥ 0.5 mg/l) with the generic and the innovator itraconazole at 2 weeks after treatment initiation. We performed a multivariate logistic regression analysis to ascertain if the trough itraconazole levels affected the treatment outcomes. We also performed morphometric analysis of different brands of itraconazole by video dermoscopy.ResultsA total of 193 [generic brands (n = 94) and innovator itraconazole (n = 99)] subjects of CPA were enrolled. The median (IQR) age of the study population [54% (105/194) men] was 42 (32-55) years. The proportion of subjects who achieved therapeutic trough itraconazole levels was significantly (P <.0001) higher with the innovator than the generic brands [72/99 (73%) vs. 27/94 (29%)]. The median trough itraconazole level at 2-weeks was also higher with the innovator brand than the generic brands [0.8 (0.5-1.6) vs. 0 (0.0.5) mg/l]. The average trough itraconazole levels and the trough itraconazole levels >1 mg/l independently predicted favorable treatment response after adjusting for age, gender, and CPA severity. The generic brands had a variable number, size, and a larger pellet size on the morphometric analysis. Two brands had dummy particles.Table 1.Outcomes.Total (n = 193)Generic drug, (n = 94)Innovator molecule (n = 99) P-valuePrimary outcomeProportion of subjects achieving ≥0.5 mg/l at 2 weeks99 (51.3)27 (28.7)72 (72.7)<.0001Secondary outcomesItraconazole levels at 14 days, mg/l0.5 (0-1)0 (0-0.5)0.8 (0.5-0.1.6)<.0001Average itraconazole levels, mg/l1.4 (0.7-2.4)0.8 (0.4-1.3)2.1 (1.2-2.8)<.0001Proportion of subjects achieving average itraconazole ≥1 mg/l98 (50.8)24 (25.5)74 (74.7)Adverse events, n (%)43 (22.3)23 (24.5)20 (20.2).494* A total of 27 subjects with generic drug achieved therapeutic drug levels and were not given the innovator molecule.ConclusionSignificantly higher proportion of subjects achieved therapeutic drug levels with the innovator brand of itraconazole than the generic brands. Importantly, the serum itraconazole levels independently predicted a favorable response to treatment in CPA.