Ipratropium/Salbutamol Comparator Versus Originator for Chronic Obstructive Pulmonary Disease Exacerbations: USA Observational Cohort Study Using the Clinformatics™ Health Claims Database

Introduction: Affordable treatment alternatives are needed to prevent and treat chronic obstructive pulmonary disease (COPD) exacerbations and reduce the economic burden of COPD. This study evaluated whether the effectiveness of Steri-Neb™ (Teva Pharmaceuticals, Inc.), the comparator ipratropium/salbutamol (I/S) nebulizer solution, is non-inferior to DuoNeb^® (Mylan Specialty L.P.), the originator with the same chemical composition, the first FDA-approved product of this kind, for the prevention of COPD exacerbations. I/S comparator versus originator safety also was examined. Both the I/S comparator and the originator are indicated (EU/USA) for bronchospasm management in patients with COPD. Methods: This matched, historical USA cohort study used Clinformatics™ claims data and included a 1-year baseline, starting 1 year before the index prescription date, and 1-year outcome period. Patients received either I/S comparator or originator treatment. The primary outcome was rate of moderate and severe COPD exacerbations. Non-inferiority for I/S comparator versus originator was satisfied if the 95% confidence interval (CI) upper limit for mean difference in proportions between treatments was <15%. The secondary outcome examined safety through rate of adverse events (AEs). Results: After matching, 550 I/S comparator and 1535 originator patients were included. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate and severe exacerbations between I/S comparator and originator cohorts was 0.092 (9.2%), and for severe exacerbations was 0.040 (4.0%), demonstrating non-inferiority. No significant differences were found in rates of moderate and severe exacerbations (rate ratio [RR] 0.96; 95% CI 0.89, 1.04), severe exacerbations (RR 1.00; 95% CI 0.81, 1.24), or any AE (RR 1.06; 95% CI 0.92, 1.22) after adjusting for baseline confounders. Conclusion: The real-world clinical outcomes of this matched cohort study support the I/S comparator as non-inferior to the originator, providing an effective and safe treatment alternative for COPD exacerbations. Study Registration: European Network Centres for Pharmacoepidemiology and Pharmacovigilance: ENCePP/SDPP/7753. Funding: Teva Branded Pharmaceutical Products, R&D, Inc.