Indacaterol/glycopyrronium reduces the risk of clinically important deterioration after direct switch from baseline therapies in patients with moderate COPD: a post hoc analysis of the CRYSTAL study

Abstract

Purpose

COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function. Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy. This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting β₂-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID.

Methods

CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings. Three definitions of CID (D1–D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV₁), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD). In D1 and D2, either TDI or CCQ was evaluated along with FEV₁ and AECOPD, whereas in D3, all 4 parameters were included. ClinicalTrials.gov number: NCT1985334.

Results

Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments. The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30–0.55]; D2: OR 0.41 [95% CI: 0.31–0.55]; D3: OR 0.39 [95% CI: 0.29–0.52]). Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56–1.02]; D2: OR 0.75 [95% CI: 0.56–1.00]; D3: OR 0.67 [95% CI: 0.51–0.89]).

Conclusion

In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice.

Keywords:

• clinically important deterioration/CID
• direct-switch
• pragmatic
• open-label
• clinical COPD questionnaire/CCQ
• transition dyspnea index/TDI

Acknowledgments

Writing and editorial assistance for this manuscript was provided by Santanu Bhadra and Vivek Khanna (Novartis Healthcare Pvt. Ltd., India). The study was supported and funded by Novartis. None of the authors received any compensation for the development of the manuscript.

Disclosure

TG has received compensation from Novartis during the conduct of the study. He has also received lecture fees from AstraZeneca, Chiesi, CSL-Behring, GlaxoSmithKline, Grifols, Mundipharma, and Novartis, and received compensation for organizing or participating in advisory boards from AstraZeneca, CSL-Behring, Novartis, Boehringer Ingelheim and Grifols, and received a grant to support an AATD-Lab from Grifols. KK has previously received honoraria for speeches and consulting services from AstraZeneca, Chiesi, ELPEN, and Takeda, and received honoraria for speeches from Boehringer Ingelheim outside the submitted work. MG has received a grant and personal fees from Novartis, Pharmaten and Menarini, outside the sub mitted work. She has also received personal fees from Chiesi, Boehringer Ingelheim and Teva, and received compensation for organizing or participating in advisory boards from GlaxoSmithKline, and received a grant from AstraZeneca. XN and VAP were statisticians for this subgroup analysis of the CRYSTAL study and work at a Novartis contracted CRO. CFV has received personal fees from Novartis during the conduct of the study. Outside the submitted work, he has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Menarini, Mundipharma and Teva, and grants from GlaxoSmithKline and Grifols.

KK is an employee and shareholder of Novartis Pharma AG. MA-M and NL are employees of Novartis Pharma AG. AC and FP are employees and shareholders of Novartis Pharma AG. RF is an employee and shareholder of Novartis Pharmaceutical Corporation. The authors report no other conflicts of interest in this work.

Author contributions

All authors have contributed substantially in data interpretation, development and revision of manuscript draft, and have provided their consent and approval for publishing this manuscript.