Triple Therapy Beneficial in Smokers and Non-Smokers with COPD : Indian Real-World Study

30 Oct, 20

Introduction

Fixed-dose triple therapy comprising long-acting beta-2-receptor agonist (LABA), long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid (ICS) have demonstrated improvement in pulmonary function and quality of life as well as reduction in chronic obstructive pulmonary disease (COPD) exacerbations. There are randomized controlled trials (RCTs) which have evaluated the outcomes of triple therapy in COPD patients with a history of smoking. However, it is well established that COPD occurs in non-smokers too. There are no Indian studies which have assessed the efficacy of triple therapy in non-smokers with COPD.

Aim

This study assesses the real-world efficacy and safety of once-daily fixed-dose triple combination of tiotropium/formoterol/ciclesonide (TFC) via a pressurized metered-dose inhaler (pMDI) or dry powder inhaler (DPI) in smokers as well as non-smokers with COPD.

Methods

Study Design

Prospective, open-label, multicenter, non-comparative, real-world study

Patient Profile

Males and females >40 years of age with a confirmed diagnosis of COPD as per GOLD 2014 criteria
The patients were enrolled irrespective of disease severity, duration, bronchodilator reversibility, smoking history and comorbidities
Newly diagnosed, treatment-na?ve and triple-therapy-na?ve patients with clinical deterioration or frequent exacerbations

Treatment Strategy

The patients underwent treatment with the triple therapy for 24 weeks
The physician prescribed TFC either via pMDI or DPI
The total daily dose delivered was 18 mcg of tiotropium, 12 mcg of formoterol and 400 mcg of ciclesonide as two puffs from the pMDI or one capsule through the DPIs
Correct usage of the inhaler device was taught to all the patients
Rescue medication (i.e. inhaled salbutamol or levosalbutamol or levosalbutamol/ipratropium FDC via a pMDI or DPI) was permitted to use as and when required
The cohort underwent spirometry test at baseline and at week 4, 8, 12, 18 and 24

Endpoints

Primary Endpoint

Mean change from baseline in pre-dose forced expiratory volume in 1 second (FEV1) at week 24

Secondary Endpoints

Mean change in the following parameters from baseline at weeks 4, 8, 12 and 18
- Pre-dose value of FEV₁
- Post-dose value of FEV₁
- Forced vital capacity (FVC)
- COPD Assessment Test (CAT) score
- Modified Medical Research Council (mMRC)

Results

A total of 253 out of 297 patients completed the study
Cohort characteristics – mean age 61+10 years, 84.8% males, 55.2% smokers and post-dose % predicted FEV1 39+16%
Triple therapy resulted in significantly increased mean change in pre-dose FEV1 from baseline to week 24 (580+600 ml); p<0.0001
Significant increase in pre and post-dose FEV1 and pre and post-dose FVC were demonstrated at all time-points (p<0.0001 for all)
The 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 the mMRC scores at week 24 (-0.77; p < 0.001)
Adverse events were reported by 21.9%
The post-hoc analysis revealed significant improvement in pre-dose FEV₁ by 200 ± 430 mL (p < 0.001) and by 990 ± 470 mL (p < 0.0001) at week 24 in smokers and non-smokers respectively, this difference being significant from week 12 onwards
Mean change in the pre and post-dose FEV1 and FVC was significant in both the groups
The improvement in CAT scores at 24 weeks was 5.17 from baseline in smokers versus 8.05 in non-smokers, with the mean difference of 2.88 (p < 0.0001) at week 24
There was no difference in the mean change in the mMRC score between smokers and non-smokers at 24 weeks.
Triple therapy was well tolerated by all patients

Conclusion

Triple therapy with the once-daily combination of TFC (tiotropium/formoterol/ciclesonide) resulted in improvements in pulmonary function and health status in patients with COPD.
The effects were more pronounced in non-smokers as compared with smokers, suggesting that non-smokers with COPD might benefit from added treatment with inhaled corticosteroid.

Pulm Pharmacol Ther. 2020 Aug; 63:101932. Doi: 10.1016/j.pupt.2020.101932.