Efficacy and safety of glycopyrrolate in patients with COPD by reversibility: pooled analysis of GEM1 and GEM2 12-week studies

Abstract

Purpose

Bronchodilator reversibility has been reported in patients with COPD, although correlations between reversibility and treatment response are unclear. The effect of reversibility on lung function, health status, and dyspnea was assessed in patients with moderate-to-severe COPD receiving glycopyrrolate (GLY) 15.6 µg twice daily vs placebo in the Glycopyrrolate Effect on syMptoms and lung function 1 and 2 (GEM1 and GEM2) replicate, 12-week, placebo-controlled studies.

Patients and methods

Reversibility was defined as a post-bronchodilator increase of ≥12% and ≥0.200 L in FEV₁. FEV₁ area under the curve from 0 to 12 hours (AUC0–12 h), trough FEV₁, 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 by reversibility status. Incidences of adverse events and serious adverse events were also assessed.

Results

Data from 846 patients enrolled in GEM1 and GEM2 with known reversibility status were pooled for post hoc analysis. GLY significantly improved FEV₁ AUC0–12 h, trough FEV₁, SGRQ and CAT total scores, and rescue medication use compared with placebo in reversible and nonreversible patients. Significant improvements in TDI focal score and daily symptom scores with GLY over placebo were observed only among reversible patients. Improvements in FEV₁ AUC0−12 h (0.165 vs 0.078 L; P<0.001) and trough FEV₁ (0.173 vs 0.070 L; P<0.001) were clinically relevant (based on minimal clinically important differences) and significantly greater in reversible compared with nonreversible patients receiving GLY. The safety profile of GLY was not affected by reversibility status.

Conclusion

In this post hoc analysis, GLY was associated with significant improvements in lung function and patient-reported outcomes compared with placebo, mostly independent of reversibility status. In patients receiving GLY, improvements in lung function were greater in reversible compared with nonreversible patients. Reversibility status did not meaningfully impact the safety profile of GLY.

Keywords:

• bronchodilator
• COPD
• glycopyrrolate
• reversibility

Supplementary material

Table S1 LSM change from baseline in trough FEV₁ (L) by reversibility status and ICS use at baseline (FAS)

Acknowledgments

This post hoc analysis was funded by Sunovion Pharmaceuticals Inc. Medical writing support was provided by Hashem Dbouk, PhD, of FireKite, an Ashfield company, part of UDG Healthcare plc, and funded by Sunovion Pharmaceuticals Inc.

Disclosure

JAO has served on advisory boards for Sunovion Pharmaceuticals Inc., AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Mylan, and Theravance, and has provided expert witness testimony for Wallace & Graham; Levy Konigsberg; Goldenberg Heller & Antognoli; Simon Greenstone Panatier Bartlett; Williams Kherkher Hart; Gori Julian & Associates; Simmons Hanly Conroy; and Elrod Pope. AB, TG, BP, AO-G, SSh, and SSa are employees of Sunovion Pharmaceuticals Inc. The authors report no other conflicts of interest in this work.