Efficacy Evaluation for Initial Maintenance Therapy in Chronic Pulmonary Aspergillosis

aspergillus flavus
aspergillus flavus

Oral voriconazole may be more effective than oral itraconazole for initial maintenance therapy in patients with chronic pulmonary aspergillosis, according to a study published in Clinical Infectious Diseases.1

Currently, there are 4 oral anti-Aspergillus agents available (itraconazole, voriconazole, posaconazole, and isavuconazole) and while various studies have evaluated treatments for chronic pulmonary aspergillosis with itraconazole and voriconazole,2-7 there are no direct comparisons for which of the 2 regimens is more appropriate for chronic pulmonary aspergillosis maintenance therapy. As such, researchers conducted a retrospective, observational, follow-up study using data from 2 previous randomized, multicenter, open-label trials conducted in Japan8,9 to compare the efficacy of itraconazole vs voriconazole.

In these 2 studies, after the end of the acute phase of intravenous antifungal treatment, the first selection of oral azole was defined as initial maintenance therapy. Of the 273 patients with chronic pulmonary aspergillosis, 59 received oral itraconazole and 101 received voriconazole. The median observation period was 731 days.

Although it was not found to be significant, the duration of therapy was longer in the itraconazole group vs voriconazole group (212 vs 116 days; P =.110). At the end of the observation period, improvement was lower in the itraconazole vs voriconazole group (18.2% vs 40%), however, after including patients with stable disease, the percentages were similar (50.9% and 52.6%, respectively) with no statistical difference (P =.174).  

Cox regression analysis showed no significant influence of the choice of initial maintenance therapy on overall mortality or on chronic pulmonary aspergillosis-associated mortality. However, the presence of chronic obstructive pulmonary disease or a higher Charlson comorbidity index was a risk factor for overall death (P =.001 for both).

Alternatively, multivariable logistic regression analysis showed that oral itraconazole was independently associated with increased need for both hospital readmission (odds ratio [OR], 3.1; 95% CI, 1.28-7.52; P =.012) and a switch to another antifungal agent as a result of insufficient efficacy (OR 5.67; 95% CI, 2.04-15.71; P =.001).

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One possible factor for the lack of significant intergroup difference in mortality may have been a predominantly elderly study population; causes for mortality were more commonly associated with diseases such as cancer and exacerbation of chronic respiratory failure rather than with chronic pulmonary aspergillosis. Researchers also noted that although itraconazole 400 mg/day is usually the recommended dosage for chronic pulmonary aspergillosis treatment, the median dosage in this study was 200 mg/day due to concerns regarding excessively high blood concentration of itraconazole because most patients had low body mass index.

Large randomized trials are needed to confirm these findings, and since chronic pulmonary aspergillosis is a rare disease, “future trials will need the support of multinational research collaborations.” In the meantime, this study provides “useful information to physicians about selection of oral antifungals at the start of treatment for [chronic pulmonary aspergillosis]” and the “various factors that should be considered when deciding on oral maintenance therapy.”


1. Tashiro M, Takazono T, Saijo T, et al. Selection of oral antifungals for initial maintenance therapy in chronic pulmonary aspergillosis: a longitudinal analysis [published online April 9, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz287

2. Agarwal R, Vishwanath G, Aggarwal AN, Garg M, Gupta D, Chakrabarti A. Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature. Mycoses. 2013;56(5):559-570.

3. Cadranel J, Philippe B, Hennequin C, et al. Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial. Eur J Clin Microbiol Infect Dis. 2012;31(11):3231-3239.

4. Camuset J, Nunes H, Dombret MC, et al. Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients. Chest. 2007;131(5):1435-1441.

5. Jain LR, Denning DW. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J Infect. 2006;52(5):e133-137.

6. Saito T, Fujiuchi S, Tao Y, et al; NHO Pulmonary Fungosis Research Group. Efficacy and safety of voriconazole in the treatment of chronic pulmonary aspergillosis: experience in Japan. Infection. 2012;40(6):661-667.

7. Yoshida K, Kurashima A, Kamei K, et al. Efficacy and safety of short-and long-term treatment of itraconazole on chronic necrotizing pulmonary aspergillosis in multicenter study. J Infect Chemother. 2012;18(3):378-385.

8. Kohno S, Izumikawa K, Ogawa K, et al; Japan Chronic Pulmonary Aspergillosis Study Group (JCPASG). Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan. J Infect. 2010;61(5):410-418.

9. Kohno S, Izumikawa K, Ogawa K, et al; Japan Chronic Pulmonary Aspergillosis Study Group (JCPASG). Intravenous liposomal amphotericin B versus voriconazole for chronic pulmonary aspergillosis: a multicenter trial in Japan. Acta Medica Nagasakiensia. 2018;61(4):167-176.