M Tashiro, T Takazono, T Saijo, K Yamamoto, Y Imamura, T Miyazaki, H Kakeya, T Ando, K Ogawa, K Kishi, I Tokimatsu, Y Hayashi, S Fujiuchi, K Yanagihara, Y Miyazaki, K Ichihara, S Kohno, K Izumikawa


There is still no evidence which of oral anti-Aspergillus agent is suitable for initial maintenance therapy of chronic pulmonary aspergillosis (CPA). Aim of this study is to clarify which of oral itraconazole and voriconazole is appropriate for initial maintenance therapy of CPA by longitudinal analysis.
This is a retrospective follow-up observational study in CPA patient enrolled to past two randomized, multicenter, open-labeled trials, one of which compared efficacy of intravenous micafungin and intravenous voriconazole, and another one of which compared efficacy of liposomal amphotericin B and intravenous voriconazole. In those studies, patients received intravenous antifungal treatment for at least 2 weeks with a maximum duration of 4 weeks. After the end of those acute phase treatment, each primary physician decided on courses of maintenance therapy and followed up patients. The median observational period was 730 days (5%-95%: 267–1407) for patients who were alive at the end of observation.
Of the 273 CPA patients, 59 patients started maintenance therapy by oral itraconazole and 101 patients started by oral voriconazole just after the end of acute intravenous therapy. Percentage of patient with improvement was seemed to be higher in voriconazole group than itraconazole group (40.0% vs 18.2%); however, if patients with stable status were added to improved patients, no statistical difference was seen (52.6% vs 50.9%). Patients who were administered itraconazole group were more likely to readmit in hospital and switch to other antifungal agent than that of voriconazole group (P = 0.020, P <0.001, respectively). Multivariable Cox regression analysis showed no significant influence of choice of initial maintenance treatment (itraconazole or voriconazole) in not only overall mortality but also CPA associated mortality. Instead, presence of chronic obstructive pulmonary diseases showed high HR 4.2 (95% CI, 1.4–12.6) in death associated with CPA. Higher efficacy rate of antifungals showed low HR 0.65 (95% CI, 0.44–0.97) in death associated with CPA. The factors associated with hospital readmission and switching rate to other antifungals were evaluated using multivariable logistic regression. It showed the facts that selection of itraconazole for initial maintenance therapy was independent risk factor for hospital readmission and switching to other antifungal agents (OR 3.3, 95% CI 1.3–8.0; OR 5.6, 95% CI 2.1–15.1, respectively). Higher efficacy rate of antifungals reduced risk of hospital readmission (OR 0.7, 95% CI 0.5–0.9).
There was no difference in prognosis of CPA patients between initial maintenance therapy of itraconazole and voriconazole. However, patients who were started with oral itraconazole treatment were more likely to readmit to the hospital and switch to other agents than patients started by oral voriconazole treatment.


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7th Advances Against Aspergillosis Conference