Efficacy and safety of high-dose budesonide/formoterol in patients with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplant.

Background: Bronchiolitis obliterans syndrome (BOS) is a rare, progressive and irreversible airway disease associated with significant mortality after allogeneic hematopoietic stem-cell transplantation (HSCT). In this study, we investigated the therapeutic effect of high-dose budesonide/formoterol (320/9 µg bid) in patients with BOS after HSCT already using low-dose budesonide/formoterol (160/4.5 µg bid).

Methods: After a retrospective chart review, patients who were initially treated with budesonide/formoterol 160/4.5 µg bid and increased their dose to 320/9 µg bid between March 2009 and February 2019 were enrolled. Pulmonary function test (PFT) and COPD assessment test (CAT) were performed before and after changing the drug dose. Efficacy was assessed within 3 months after increasing the drug dose; the primary variable was changes in forced expiratory volume in 1 second (FEV1) and CAT score. Safety was assessed as the incidence of pneumonia within 3 months after increasing the drug dose.

Results: Seventy-seven patients were treated with budesonide 160 µg plus formoterol 4.5 µg twice a day for more than 3 months and the dose was increased to budesonide 320 µg plus 9.0 µg twice a day. After treatment with high-dose ICS/LABA (budesonide 320 µg plus formoterol 9.0 µg twice a day for 12 weeks), there were no significant differences in FEV1 (before treatment 1.59 L vs. after treatment 1.65 L, P=0.182) or FVC (before treatment 2.93 L vs. after treatment 2.96 L, P=0.519) compared to before starting the high dose treatment. There were no significant differences in the total CAT score. Of all patients, 34.2% of patients had an increase in FEV1 ≥100 mL and 35.3% of patients showed a decrease ≥2 points in CAT score. In safety assessment, there were no significant differences between the two periods.

Conclusions: Our study failed to show superior effect of high-dose budesonide/formoterol (320/9 µg) compared with low-dose. However, high-dose budesonide/formoterol was safe and there was no lung function deterioration.