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A3025 - Seebri™ Neohaler® (Glycopyrrolate) Versus Placebo in Patients with Moderate to Severe COPD: Analysis of Health-Related Quality of Life (HRQoL) from the GEM1 Study
Author Block: G. Feldman1, C. Dembek2, K. Rajagopalan2; 1South Carolina Pharmaceutical Research, Spartanburg, SC, United States, 2Sunovion Pharmaceuticals Inc., Marlborough, MA, United States.
Rationale: Chronic obstructive pulmonary disease (COPD), characterized by progressive loss of lung function, is known to adversely impact HRQoL. The aim of long-acting maintenance treatments, such as glycopyrrolate (a long-acting muscarinic antagonist), is to reduce COPD symptoms and frequency and severity of exacerbations, and improve HRQoL. The impact of twice-daily glycopyrrolate on HRQoL as measured by St. George’s Respiratory Questionnaire (SGRQ) is presented here. Methods: Data from GEM1, one of two 12-week, randomized, double-blind, placebo-controlled confirmatory trials evaluating the safety and efficacy of twice-daily glycopyrrolate 15.6 µg are presented. Stable, symptomatic patients ≥40 years old with moderate to severe COPD were included. The SGRQ, a 50-item patient-reported HRQoL measure, was collected at baseline and 12 weeks. The SGRQ comprises three components that measure: (i) distress due to respiratory symptoms (“Symptoms”); (ii) effects of disturbances to mobility and physical activity (“Activity”), and (iii) psychosocial impact of the disease (“Impacts”). Component scores and the total score are expressed as a mean of the specific items on a scale of 0-100; lower scores indicate improvement in HRQoL. A reduction of ≥4 units in SGRQ total score is defined as the minimum clinically important difference (MCID). Patients reaching MCID in total score are defined as responders. Change from baseline to week 12 in total and component scores was analyzed using a linear mixed model with treatment, baseline SGRQ, smoking status, and inhaled corticosteroid use as fixed effects, and center as a random effect. The proportion of patients achieving the MCID in SGRQ total score was analyzed using a logistic regression model. Results: In total, 441 patients (222 glycopyrrolate, 219 placebo) were enrolled. Statistically significant improvements were observed with glycopyrrolate versus placebo for the total score (least squares mean treatment difference [standard error] −2.8 [1.14], 95% confidence interval [CI] −5.0, −0.5, P=0.016), the Symptoms component (−3.8 [1.66], 95% CI −7.0, −0.5, P=0.025), and the Activity component (−4.2 [1.36], 95% CI −6.9, −1.5, P=0.002). Mean change in the Impacts component was greater with glycopyrrolate versus placebo; however, the difference was not statistically significant (−3.8 vs −1.8, P=0.128). A higher proportion of patients receiving glycopyrrolate achieved the MCID for total score (49.0%) versus placebo (40.6%; P=0.083). Conclusions: In one of two confirmatory studies, Seebri Neohaler (glycopyrrolate) demonstrated greater or significantly greater improvements in SGRQ total score and Symptoms, Activity, and Impacts components and had a higher proportion of patients attain MCID in total score versus placebo.