Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study

OBJECTIVE: To compare the effectiveness and safety of budesonide-glycopyrrolate-formoterol, a twice daily metered dose inhaler, and fluticasone-umeclidinium-vilanterol, a once daily dry powder inhaler, in patients with chronic obstructive pulmonary disease (COPD) treated in routine clinical practice. DESIGN: New user cohort study. SETTING: Longitudinal commercial US claims data. PARTICIPANTS: New initiators of budesonide-glycopyrrolate-formoterol or fluticasone-umeclidinium-vilanterol between 1 January 2021 and 30 September 2023 who had a diagnosis of COPD and were aged 40 years or older. MAIN OUTCOME MEASURES: In this 1:1 propensity score matched study, the main outcome measures were first moderate or severe COPD exacerbation (effectiveness) and first admission to hospital with pneumonia (safety) while on treatment. Potential confounders were measured in the 365 days before cohort entry and included in propensity scores. Hazard ratios and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards regression model. RESULTS: The study cohort included 20 388 propensity score matched pairs of new users initiating single inhaler triple therapy. Patients who received budesonide-glycopyrrolate-formoterol had a 9% higher incidence of first moderate or severe COPD exacerbation (hazard ratio 1.09 (95% CI 1.04 to 1.14); number needed to harm 38) compared with patients receiving fluticasone-umeclidinium-vilanterol and an identical incidence of first admission to hospital with pneumonia (1.00 (0.91 to 1.10)). The hazard of first moderate COPD exacerbation was 7% higher (1.07 (1.02 to 1.12); number needed to harm 54) and the hazard of first severe COPD exacerbation 29% higher (1.29 (1.12 to 1.48); number needed to harm 97) among those receiving budesonide-glycopyrrolate-formoterol compared to fluticasone-umeclidinium-vilanterol. Prespecified sensitivity analyses yielded similar findings to the primary analysis. CONCLUSIONS: Budesonide-glycopyrrolate-formoterol was not associated with improved clinical outcomes compared with fluticasone-umeclidinium-vilanterol. Given the added climate impact of metered dose inhalers, health systems seeking to decrease use of these products may consider steps to promote further prescribing of fluticasone-umeclidinium-vilanterol compared with budesonide-glycopyrrolate-formoterol in people with COPD. STUDY REGISTRATION: Center for Open Science Real World Evidence Registry (https://osf.io/6gdyp/).