Real-world evaluation of adherence to single-inhaler triple therapy in chronic obstructive pulmonary disease: the LIFE Study

Adherence and persistence for inhaled maintenance therapy markedly influence outcomes in chronic obstructive pulmonary disease (COPD). However, real-world data for single-inhaler triple therapy (SITT), including the effects of prior controller use and the selected regimen, have been limited. We here aimed to evaluate real-world adherence and persistence for SITT in COPD and to examine differences according to prior controller use and inhaler regimen. Using the population-based LIFE Study administrative claims database in Japan, we conducted a retrospective cohort study of patients with COPD who newly initiated budesonide-glycopyrronium-formoterol (BGF) or fluticasone furoate–umeclidinium–vilanterol (FUV) between April 2020 and March 2022. Medication adherence over 12 months was assessed according to the proportion of days covered (PDC), with good adherence defined as a PDC of ≥ 0.80. Multivariable-adjusted risk ratios (RRs) for good adherence were estimated by modified Poisson regression. Treatment persistence was evaluated as time to discontinuation determined by Kaplan-Meier analysis with inverse probability of treatment weighting (IPTW), and differences were quantified as restricted mean survival time (RMST) over 365 days. Among 4077 individuals initiating SITT, only 36.4% achieved good adherence during the 12-month follow-up period. Controller-naïve patients were substantially less likely to achieve good adherence than patients with prior controller use (multivariable-adjusted RR, 0.37; 95% CI, 0.34–0.41). Treatment persistence was also worse for controller-naïve patients, with an IPTW-adjusted RMST that was 3.42 months shorter than that for patients with prior controller use (95% CI, − 3.67 to − 3.15 months). With respect to regimen, FUV was associated with a higher likelihood of good adherence compared with BGF (multivariable-adjusted RR, 1.40; 95% CI, 1.28–1.52) and showed longer treatment persistence (IPTW-adjusted RMST difference of 0.49 months; 95% CI, 0.22–0.76 months). Adherence and persistence for SITT were suboptimal among patients with COPD in real-world clinical practice, particularly among controller-naïve individuals. Although the once-daily FUV regimen was associated with better adherence and persistence than BGF, substantial gaps in treatment continuity persisted with both regimens. These findings highlight the need for enhanced support at treatment initiation and during early follow-up to optimize long-term SITT use in routine COPD care.