David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.
Respir Res. 2019 Jul 2;20(1):135. doi: 10.1186/s12931-019-1112-0.
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.
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 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 (FEV) area under the curve from 0 to 12 h, trough FEV, 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.
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 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.
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.
吸烟是 COPD 的一个主要危险因素，可能会影响 COPD 治疗的效果；然而，很大一部分 COPD 患者在确诊后仍继续吸烟。
本研究对重复的 12 周、安慰剂对照的 GEM1 和 GEM2 研究的汇总数据进行了事后分析，评估了吸烟状况对格隆溴铵 15.6μg 每日两次与安慰剂治疗中重度 COPD 患者的疗效和安全性的影响。来自 GEM1 和 GEM2 的 867 名患者的数据被汇总进行分析，并按吸烟状况分组（57%为当前吸烟者，43%为戒烟者）。从 0 到 12 小时的用力呼气量（FEV）曲线下面积、谷值 FEV、用力肺活量、圣乔治呼吸问卷（SGRQ）总分、COPD 评估测试（CAT）评分、呼吸困难指数（TDI）焦点评分、每日症状评分和急救药物使用情况在当前吸烟者和戒烟者中进行评估。还评估了不良事件（AE）和严重不良事件（SAE）的发生率。
格隆溴铵治疗可显著改善所有肺功能指标，与吸烟状态无关。在当前吸烟者和戒烟者中，与未接受吸入性皮质类固醇（ICS）治疗的患者相比，接受 ICS 治疗的患者谷值 FEV 的变化较小。与安慰剂相比，格隆溴铵治疗后 SGRQ 总分和急救药物使用的变化显著更大，无论吸烟状态如何。与安慰剂相比，CAT 评分、TDI 焦点评分和每日症状评分的变化均显著改善，但仅在当前吸烟者中。与安慰剂相比，格隆溴铵治疗后患者报告的结局（PROs）的改善在当前吸烟者中数值上大于戒烟者。AE 和 SAE 的发生率与吸烟状态无关。
在 GEM1 和 GEM2 的这项事后分析中，使用格隆溴铵可显著改善肺功能，与基线吸烟状态无关；无论基线吸烟状态如何，接受背景 ICS 治疗的患者的改善程度较小。与安慰剂相比，格隆溴铵治疗可显著改善 PROs，且在当前吸烟者中变化程度数值上更大。格隆溴铵的安全性在当前吸烟者和戒烟者中相似。
