PMID- 31266489 OWN - NLM STAT- MEDLINE DCOM- 20200106 LR - 20200225 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 20 IP - 1 DP - 2019 Jul 2 TI - Effect of smoking status on lung function, patient-reported outcomes, and safety among COPD patients treated with glycopyrrolate inhalation powder: pooled analysis of GEM1 and GEM2 studies. PG - 135 LID - 10.1186/s12931-019-1112-0 [doi] LID - 135 AB - BACKGROUND: Smoking is a major risk factor for COPD and may impact the efficacy of COPD treatments; however, a large proportion of COPD patients continue to smoke following diagnosis. METHODS: This post-hoc analysis of pooled data from the replicate 12-week, placebo-controlled GEM1 and GEM2 studies assessed the impact of smoking status on the efficacy and safety of glycopyrrolate 15.6 mug twice daily vs placebo in patients with moderate-to-severe COPD. Data from 867 patients enrolled in GEM1 and GEM2 were pooled for analysis and grouped by smoking status (57% current smokers, 43% ex-smokers). Forced expiratory volume in 1 s (FEV(1)) area under the curve from 0 to 12 h, trough FEV(1), forced vital capacity, St George's Respiratory Questionnaire (SGRQ) total score, COPD assessment test (CAT) score, transition dyspnea index (TDI) focal score, daily symptom scores, and rescue medication use were assessed in current smokers and ex-smokers. Incidences of adverse events (AEs) and serious AEs (SAEs) were also assessed. RESULTS: Treatment with glycopyrrolate resulted in significant improvements in all lung function measures, independent of smoking status. In both current and ex-smokers, changes from baseline in trough FEV(1) were less marked in patients taking inhaled corticosteroids (ICS) than those not receiving ICS. Changes from baseline in SGRQ total score and rescue medication use were significantly greater with glycopyrrolate compared with placebo, regardless of smoking status. Changes in the CAT score, TDI focal score, and daily symptom scores significantly improved versus placebo, but only in current smokers. Improvements in patient-reported outcomes (PROs) with glycopyrrolate relative to placebo were numerically greater in current smokers than ex-smokers. The incidences of AEs and SAEs were similar regardless of smoking status. CONCLUSIONS: In this post-hoc analysis of GEM1 and GEM2, glycopyrrolate use led to significant improvements in lung function, independent of baseline smoking status; improvements were less marked among patients receiving background ICS, regardless of baseline smoking status. Improvements in PROs were greater with glycopyrrolate than placebo, and the magnitude of changes was numerically greater among current smokers. The safety profile of glycopyrrolate was comparable between current smokers and ex-smokers. FAU - Tashkin, Donald P AU - Tashkin DP AD - David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. dtashkin@mednet.ucla.edu. FAU - Goodin, Thomas AU - Goodin T AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. FAU - Bowling, Alyssa AU - Bowling A AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. FAU - Price, Barry AU - Price B AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. FAU - Ozol-Godfrey, Ayca AU - Ozol-Godfrey A AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. FAU - Sharma, Sanjay AU - Sharma S AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. FAU - Sanjar, Shahin AU - Sanjar S AD - Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20190702 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Bronchodilator Agents) RN - V92SO9WP2I (Glycopyrrolate) SB - IM MH - Administration, Inhalation MH - Aged MH - Bronchodilator Agents/*administration & dosage MH - Double-Blind Method MH - Female MH - Glycopyrrolate/*administration & dosage MH - Humans MH - Lung/*drug effects/physiology MH - Male MH - Middle Aged MH - *Patient Reported Outcome Measures MH - Tobacco Smoking/*drug therapy/physiopathology MH - Treatment Outcome MH - Vital Capacity/*drug effects/physiology PMC - PMC6604131 OTO - NOTNLM OT - Bronchodilator OT - COPD OT - Glycopyrrolate OT - LAMA OT - Lung function OT - Patient-reported outcomes OT - Safety OT - Smoking status COIS- DPT has received non-financial support from Sunovion Inc. during the conduct of this study and personal fees from Sunovion Inc., AstraZeneca, Boehringer Ingelheim, and Innoviva, outside the submitted work. TG, AB, BP, AO-G, SSh, and SSa are employees of Sunovion Pharmaceuticals Inc. EDAT- 2019/07/04 06:00 MHDA- 2020/01/07 06:00 PMCR- 2019/07/02 CRDT- 2019/07/04 06:00 PHST- 2019/02/06 00:00 [received] PHST- 2019/06/25 00:00 [accepted] PHST- 2019/07/04 06:00 [entrez] PHST- 2019/07/04 06:00 [pubmed] PHST- 2020/01/07 06:00 [medline] PHST- 2019/07/02 00:00 [pmc-release] AID - 10.1186/s12931-019-1112-0 [pii] AID - 1112 [pii] AID - 10.1186/s12931-019-1112-0 [doi] PST - epublish SO - Respir Res. 2019 Jul 2;20(1):135. doi: 10.1186/s12931-019-1112-0.