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Randomized Controlled Trial
. 2018 Apr 16:13:1229-1237.
doi: 10.2147/COPD.S159732. eCollection 2018.

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

Timm Greulich  1 , Konstantinos Kostikas  2 , Mina Gaga  3 , Maryam Aalamian-Mattheis  2 , Nadine S Lossi  4 , Francesco Patalano  2 , Xavier Nunez  5 , Veronica A Pagano  5 , Robert Fogel  6 , Claus F Vogelmeier #  1 , Andreas Clemens #  2   7
Affiliations
Randomized Controlled Trial

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

Timm Greulich et al. Int J Chron Obstruct Pulmon Dis. .

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: NCT01985334.

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

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Study design of the groups that switched to IND/GLY. Note: *Randomization ratio (switched:continued baseline treatments) =3:1 by stratifying background medications. Abbreviations: ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; od, once daily.
Figure 2
Figure 2
Effect of IND/GLY on CID compared with LABA or LAMA for each CID definition. Notes: *Patients had mMRC ≥2. Definitions of D1, D2, and D3 are described in Table 1. Abbreviations: CID, clinically important deterioration; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council.
Figure 3
Figure 3
Effect of IND/GLY on CID compared with LABA + ICS for each CID definition. Notes: Data are presented as odds ratio (95% CI). Definitions of D1, D2, and D3 are described in Table 1. Abbreviations: CID, Clinically important deterioration; ICS, inhaled corticosteroid; IND/GLY, indacaterol/glycopyrronium; LABA, long-acting β2-agonist.
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