Indacaterol/Glycopyrronium Superior to Salmeterol/Fluticasone in Current and Ex-Smoker Patients with COPD

3 Jun, 21

Introduction

Although the benefits of smoking cessation are known, a high proportion of patients with chronic obstructive pulmonary disease (COPD) continue to smoke. Inhaled corticosteroids (ICS) have proven to be less effective in asthmatic patients who smoke demonstrating fewer short-term lung function improvements and reduced anti-inflammatory effects as compared to non-smokers. However, there is paucity of data on the efficacy of ICS-containing regimens in COPD patients who continue smoking.

Aim

This is a pooled analysis of ILLUMINTE, LANTERN and FLAME trials to compare the efficacy of once-daily indacaterol/glycopyrronium (IND/GLY) 110/50?µg with twice-daily salmeterol/fluticasone (SFC) 50/500?µg in current and ex-smokers with COPD. This analysis also determines if smoking impairs the response to ICS in COPD.

Patient Profile

In total, 4617 patients (mean age of >60 years) were included in this pooled analysis

Current [n=1769 (38%)] and ex-smokers [n=2848 (62%)], with a smoking history of at least 10?pack-years (10?pack-years are defined as 20 cigarettes a day for 10?years, or 10 cigarettes a day for 20?years, etc.)
An ex-smoker was defined as a person who had not smoked for ≥6?months at screening.

Method

Study Design

Pooled post-hoc analysis of randomized controlled trials – ILLUMINATE, LANTERN and FLAME

Treatment Strategy

The full analysis set comprised of the following treatment groups
- Current smokers who received IND/GLY 110/50 µg once daily
- Current smokers who received SFC 50/500 µg twice daily
- Ex-smokers who received IND/GLY 110/50 µg once daily
- Ex-smokers who received SFC 50/500 µg twice daily
The efficacy endpoints were compared after week 26 common to all studies.

End Points

Lung function, assessed by improvement in pre-dose trough forced expiratory volume in 1?s (FEV₁)
Proportion of patients achieving minimal clinically important difference (MCID) of ≥100?mL increase in trough FEV₁ at Week 26
Dyspnea evaluated by improvement in transition dyspnea index (TDI) focal score & proportion of patients achieving MCID of ≥1-point increase in the score at Week 26
Health status, assessed by improvement in the St George's Respiratory Questionnaire (SGRQ) total score & proportion of patients achieving MCID of ≥4-point reduction in the score at Week 26
The change from baseline in rescue medication use over 26?weeks
Annualized rate of all (mild/moderate/severe), moderate/severe and severe exacerbations

Results

At Week 26, IND/GLY 110/50?µg once daily showed greater improvement in pre-dose trough FEV₁ versus SFC 50/500?µg twice daily in both current and ex-smokers with a difference of 0.105 points; p<0.0001 and 0.078 points; p<0.0001 (least squares mean treatment difference, 105 and 78?mL), respectively.
Both in current and ex-smokers, significantly more % of patients in IND/GLY group achieved MCID for trough FEV₁ unlike patients in SFC group (47.8% vs 26.6% in current smokers and 46.3% vs 30.7% in ex-smokers respectively)
Improvements in TDI focal score were seen in both the groups. However, the current smokers demonstrated greater improvement with a difference of 0.85 points (p=0.0013) as compared to 0.29 points (p=0.1444) in the ex-smokers.
Proportion of patients achieving MCID for TDI focal score was numerically higher with IND/GLY (76.2%) group vs SFC (67.3%) group.
A greater reduction in the SGRQ total score was seen in the IND/GLY group in current (-1.792; p=0.0019) as well as ex-smokers (-0.910; p=0.0465), with a more pronounced difference in current smokers.
Reduction in rescue medication use over 26 weeks was demonstrated by IND/GLY in current (-0.380; p=0.0001) and ex-smokers (-0.151; p=0.0271 respectively), with a greater reduction in current smokers.
Greater reduction of all exacerbations (moderate/severe) was seen with IND/GLY compared with SFC, irrespective of smoking status.

Conclusions

Indacaterol/glycopyrronium (IND/GLY) demonstrated better efficacy with respect to lung function, health-related quality of life, dyspnea, rescue medication use and exacerbations in current smokers as well as ex-smokers as compared with salmeterol/fluticasone (SFC).
The differences were generally more prominent in current smokers suggesting that smoking might decrease the effects of SFC.

ERJ Open Res. 2021 Jan; 7(1): 00816-2020. Doi: 10.1183/23120541.00816-2020.