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 microg (IND/GLY) from previous monotherapy with a long-acting beta2-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.
- Greulich, T.
- Kostikas, K.
- Gaga, M.
- Aalamian-Mattheis, M.
- Lossi, N. S.
- Patalano, F.
- Nunez, X.
- Pagano, V. A.
- Fogel, R.
- Vogelmeier, C. F.
- Clemens, A.
Keywords
- Administration, Inhalation
- Adrenal Cortex Hormones/administration & dosage
- Adrenergic beta-2 Receptor Agonists/*administration & dosage/adverse effects
- Aged
- Bronchodilator Agents/*administration & dosage/adverse effects
- Disease Progression
- *Drug Substitution
- Europe
- Female
- Forced Expiratory Volume
- Glycopyrrolate/*administration & dosage/adverse effects
- Health Status
- Humans
- Indans/*administration & dosage/adverse effects
- Lung/*drug effects/physiopathology
- Male
- Middle Aged
- Muscarinic Antagonists/*administration & dosage/adverse effects
- Prospective Studies
- Pulmonary Disease, Chronic Obstructive/diagnosis/*drug therapy/physiopathology
- Quinolones/*administration & dosage/adverse effects
- Risk Factors
- Severity of Illness Index
- Time Factors
- Treatment Outcome
- clinical COPD questionnaire/CCQ
- clinically important deterioration/CID
- direct-switch
- open-label
- pragmatic
- transition dyspnea index/TDI
- 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.
