Efficacy and Tolerability of Budesonide/Formoterol Added to Tiotropium in Patients with Chronic Obstructive Pulmonary Disease

TLDR

Budesonide/formoterol and tiotropium are widely used maintenance therapies for COPD patients. The study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium in patients eligible for inhaled corticosteroid/long‑acting β2‑agonist therapy. In a 12‑week, randomized, double‑blind, multicenter trial, 660 adults received tiotropium plus either budesonide/formoterol or placebo, with clinic and home measurements of lung function, symptoms, and exacerbations. Budesonide/formoterol added to tiotropium produced significant improvements in predose FEV1 (6 % increase), postdose FEV1 (≈11 % increase), health status, morning symptoms, and reduced severe exacerbations by 62 %, while both regimens were well tolerated. Trial registered at ClinicalTrials.gov (NCT00496470).

Abstract

Rationale: Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits.Objectives: To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting β2-agonist combination therapy.Methods: In this 12-week, randomized, double-blind, parallel-group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV1, 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 μg once daily) plus either budesonide/formoterol (320/9 μg) (n = 329) or placebo (n = 331) twice daily.Measurements and Main Results: Clinic predose (primary outcome) and postdose FEV1, predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV1 and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide/formoterol plus tiotropium significantly increased predose FEV1 by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P < 0.001). Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25–0.57; P < 0.001). Both treatments were well tolerated.Conclusions: In patients with chronic obstructive pulmonary disease, budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations.Clinical trial registered with www.clinicaltrials.gov (NCT00496470). https://www.clinicaltrials.gov (NCT00496470).