Indacaterol/glycopyrronium (IND/GLY) reduces the risk of clinically important deterioration (CID) versus open-label tiotropium (Tio) in COPD patients: Post hoc analysis from SHINE and SPARK studies

Introduction Deterioration in lung function, health status and exacerbations are predictors of COPD worsening. A composite endpoint, CID of above parameters can be an indicator of treatment effect on disease progression. We report effects of IND/GLY vs. TIO on time to first CID in patients (pts) with moderate-severe COPD. Methods Data from 2 randomised trials were analysed. CID was defined, based on minimum clinically important differences, in two ways. Definition 1 [D1]: ≥100mL decrease in FEV 1 or ≥4U increase in SGRQ total score or moderate-severe exacerbation; sustained CID defined as ≥100mL decrease in FEV 1 or ≥4U increase in SGRQ total score on 2 consecutive visits ≥4 weeks apart or ≥50% of all subsequent visits or exacerbation. In Definition 2 (D2, assessed only in SHINE), FEV 1 was replaced with ≥1U decrease in TDI. Time to first CID was also assessed in subgroups based on age, gender, smoking status, disease severity and serum eosinophils. Results Data of 2429 pts (SHINE, n=954; SPARK, n=1475) were analysed. In D1, time to first CID was significantly delayed by IND/GLY vs. TIO in SHINE (HR, 0.72; p=0.0003) and SPARK (HR, 0.87; p=0.0229. IND/GLY also significantly delayed sustained CID vs. TIO in SHINE (HR, 0.73; p=0.0013) and SPARK (HR, 0.88; p=0.0397). In D2, IND/GLY showed significant delay in time to first CID (HR, 0.74; p=0.0022) and sustained CID (HR, 0.77; p=0.0184) vs. TIO. Subgroup analysis results were consistent with overall results. Conclusion IND/GLY significantly reduced risk of CID and provided sustained efficacy in patients with moderate-severe COPD vs. TIO.