Anti-fungal agents in the treatment of chronic pulmonary aspergillosis: Systematic review and a network meta-analysis

Mycoses. 2021 May 25. doi: 10.1111/myc.13324. Online ahead of print.


Background: Oral itraconazole and voriconazole are currently recommended in the initial management of chronic pulmonary aspergillosis (CPA). However, only a few studies have compared outcomes with different anti-fungal agents (AFAs) in treating CPA. Herein, we perform a network meta-analysis comparing the efficacy of different AFAs in CPA.

Methods: We searched the PubMed and EmBase databases to identify studies (either randomised-controlled trials [RCTs] or observational) reporting treatment outcomes with AFAs in patients of CPA. The study quality was assessed using the Newcastle-Ottawa scale (NOS). We performed a network meta-analysis to compare the relative efficacy of different AFAs in treating CPA. The primary outcome was a favourable response to treatment with AFAs.

Results: We found ten studies (718 patients) investigating different AFAs (oral AFAs [n = 5], intravenous AFAs [n = 5]) in the treatment of CPA. There were four RCTs and six observational studies. The studies using oral agents reported long-term outcomes (>12 weeks), while those with intravenous agents provided only short-term outcomes (<6 weeks). We found one study of posaconazole and none with isavuconazole for treating CPA. Amongst the oral agents, itraconazole was significantly better than supportive care and was ranked as the best oral AFA on network rank analysis. We found all intravenous AFAs to be equally effective. Intravenous echinocandins and voriconazole were ranked best for achieving a favourable treatment response.

Conclusion: Oral itraconazole may be preferred over other azoles as the initial therapy for CPA. Amongst the intravenous agents, echinocandins and voriconazole may be preferred over amphotericin B. Randomised-controlled trials comparing different AFAs, especially the newer AFAs, are urgently needed.

Keywords: amphotericin B; caspofungin; itraconazole; micafungin; posaconazole; voriconazole.