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 Clemens2,7,* 1University Medical Center Giessen and Marburg, German Center for Lung Research (DZL), Marburg, Germany; 2Novartis Pharma AG, Basel, Switzerland; 37th Respiratory Medicine Department, Athens Chest Hospital Sotiria, Athens, Greece; 4Novartis Pharma GmbH, Nürnberg, Germany; 5TFS Develop, Barcelona, Spain; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Heart Center Freiburg University, Cardiology and Angiology I, Faculty of Medicine, Freiburg, Germany *These authors contributed equally to this work 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: clinically important deterioration/CID, direct-switch, pragmatic, open-label, clinical COPD questionnaire/CCQ, transition dyspnea index/TDI