Fixed-dose combination of three drugs, i.e. LABA/LAMA/ICS for COPD: Results of a real-world study from India

The use of triple therapy with inhaled corticosteroids, long-acting beta-agonist and long-acting antimuscarinics has been shown to be beneficial in COPD patients who continue to have symptoms and exacerbations, despite receiving dual bronchodilator combinations. This study assessed the real-world effectiveness and safety of once-daily, fixed-dose combination of Tiotropium/Formoterol/Ciclesonide (TFC) (18 mcg/12 mcg/400 mcg) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in patients with COPD.

In this 24-week, open-label, prospective, non-comparative, multicentre, real-world study, COPD patients requiring triple therapy as judged by their physician, were enrolled. The primary endpoint was mean change from baseline in pre-dose Forced Expiratory Volume in 1 s (FEV₁) at week 24. Pre and post-dose (30 min) FEV₁, Forced Vital capacity (FVC), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) score and safety were also evaluated. A post-hoc analysis was conducted to evaluate the efficacy of the triple drug combination among smoker and non-smoker COPD patients.

Out of the 297 patients enrolled [mean age 61 ± 10 years; 84.8% males; 55.2% smokers and post-dose FEV₁ (% predicted) 39 ± 16%], 253 completed the study. Mean change in pre-dose FEV₁ from baseline to week 24 increased significantly after administering the triple drug combination [580 ± 600 mL, 95% CI (510, 650 mL), p < 0.0001]. The increase in the pre-dose FEV₁ was significant at all time points (p < 0.0001). Similar improvements were seen in pre-dose FVC, post-dose FEV₁ and post-dose FVC across all time points. CAT scores and the proportion of patients with improved mMRC score improved at all visits. The post-hoc analysis showed that TFC significantly increased pre-dose FEV₁ both among smokers [mean change 200 ± 430 mL, 95% CI (130, 270 mL), p < 0.0001] as well as non-smokers [990 ± 470 mL, 95% CI (900, 1070 mL), p < 0.0001] at week 24. This difference was significant from week 12 onwards. Mean change in pre and post-dose FEV₁ and FVC was significant across all visits between the two groups. At week 24, CAT score reduced significantly from baseline (overall: -6.6 ± 6.07; smokers: -5.17 + 6.96; non-smokers: 8.06 ± 4.44; all p < 0.0001). The mean difference between the two groups was 2.88 (p < 0.0001) at week 24. TFC was well tolerated.

In this real world, multicentre study in India, TFC significantly improved lung function, symptoms and quality of life among all patients with COPD, but the effect was more pronounced among non-smoker COPD patients.