A Real-World Indian Study Demonstrates Efficacy and Safety of Triple Therapy in COPD Patients

Introduction

Triple therapy with long-acting inhaled corticosteroids (ICS), beta-2-receptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) has been associated with improvement in pulmonary function and quality of life as well as reduction in chronic obstructive pulmonary disease (COPD) exacerbations. Randomized controlled trials (RCTs) in COPD include patients with smoking history. India has a significant proportion of COPD patients who are non-smokers. The efficacy of triple therapy for COPD in non-smokers has not been studied.

Aim

This real-world study evaluates the efficacy and safety of once daily fixed-dose combination of tiotropium 18 mcg/formoterol 12 mcg/ciclesonide 400 mcg (TFC) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in COPD patients. A post-hoc analysis was conducted to assess the efficacy of TFC therapy among smoker and non-smoker COPD patients.

Methods

Study Design

• Open label, prospective, non-comparative, multicenter, real-world study

Treatment Strategy

• Patients >40 years of age with confirmed diagnosis of COPD, irrespective of smoking history, severity of disease, duration of disease, bronchodilator reversibility, comorbidity or other medications
• Newly diagnosed, treatment-na?ve, triple-therapy-naive COPD patients with clinical deterioration or frequent exacerbations
• Cohort underwent TFC treatment for 24 weeks
• As and when required rescue medication was permitted during the study period
• Patients underwent spirometry at 4, 8, 12, 18 and 24 weeks

Endpoints

• Mean change from baseline in pre-dose Forced Expiratory Volume in 1 second (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
• Safety

Results

• The study population enrolled 297 patients with a mean age 61 ± 10 years; 84.8% males; 55.2% smokers and post-dose FEV₁ (% predicted) 39 ± 16%
• The study was completed by 253 patients
• The triple therapy resulted in a significant increase in the mean change in pre-dose FEV₁ from baseline to week 24 (580 ± 600 mL; p < 0.0001)
• A significant increase in the pre-dose FEV₁ at all time points was noted; p < 0.0001
• Improvements were observed in pre-dose FVC, post-dose FEV₁ and post-dose FVC across all time points as seen in table 1.

• At week 24, CAT score improved significantly with a mean change of -6.56+6.07 from baseline (p<0.0001)
• At week 24, significant improvements were seen in mMRC score at all timepoints, about 30% achieved a score of 0 at week 24
• The post-hoc analysis revealed that TFC significantly increased pre-dose FEV₁ both among smokers (mean change 200 ± 430 mL; p < 0.0001) as well as non-smokers (990 ± 470 mL; p < 0.0001) at week 24. This difference was significant from week 12 onwards.
• The smokers and non-smokers demonstrated significant improvements in pre- and post-dose FEV₁ and FVC across all visits
• There was a significant reduction in the CAT score from baseline in the overall cohort -6.6 ± 6.07; smokers: -5.17 + 6.96; non-smokers: 8.06 ± 4.44; all p < 0.0001 at week 24. The mean difference between the two groups was 2.88 (p < 0.0001) at week 24
• TFC was well tolerated with 21.9% reporting adverse events

Conclusion

• Triple therapy with once-daily combination of tiotropium, formoterol and ciclesonide (TFC) significantly improved pulmonary function, symptoms, and quality of life in patients with chronic obstructive pulmonary disease (COPD), irrespective of their smoking history
• The effects were more pronounced among non-smoker COPD patients, indicating a beneficial effect of adding inhaled corticosteroid to the bronchodilators.

Pulm Pharmacol Ther 2020 Aug; 63. Doi: 10.1016/j.pupt.2020.101932.