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.

BackgroundSmoking 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.MethodsThis 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 μg 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 (FEV1) area under the curve from 0 to 12 h, trough FEV1, 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.ResultsTreatment 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 FEV1 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.ConclusionsIn 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

Action of drugs on mucociliary clearance

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Impact of baseline clinical features on outcomes of nebulized glycopyrrolate therapy in COPD

Inhaled bronchodilators are central for the treatment of chronic obstructive pulmonary disease (COPD), as they can provide symptom relief and reduce the frequency and severity of exacerbations while improving health status and exercise tolerance. In 2017, glycopyrrolate (GLY) delivered via the eFlow® closed system (CS) nebulizer (nebulized GLY; 25 µg twice daily), was approved by the US Food and Drug Administration for maintenance treatment of moderate-to-very-severe COPD. This approval was based largely on results from the replicate, placebo-controlled, Phase III clinical trials- GOLDEN 3 and 4. In this review, we summarize key findings from secondary analyses of the GOLDEN 3 and 4 studies, and provide a comprehensive overview that may assist both pulmonologists and primary-care providers in their treatment decisions. Comorbidities are common among patients with COPD in clinical practice and may impact bronchodilator efficacy. This review highlights outcomes among subpopulations of patients with comorbidities (e.g., anxiety/depression, cardiovascular disease), and their impact on the efficacy of nebulized GLY. In addition, the efficacy and safety of nebulized GLY across various demographics (e.g., age, gender) and baseline disease characteristics (e.g., disease severity, rescue medication use) are discussed. Real-world outcomes with nebulized GLY, including device satisfaction, healthcare resource utilization, and exacerbations, are also presented. These secondary analyses and real-world data complement the primary results with nebulized GLY from Phase III studies and support the need for the inclusion of patients representative of real-world clinical practice in RCTs. In addition, these data suggest that RCTs for COPD therapies should be complemented with real-world observational studies