Abstract
Introduction Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. Methods This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs. Results After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death. Conclusion This matched cohort study of real-life management of COPD patients supports the salbutamol comparator as non-inferior to the reference product, providing an effective treatment alternative for COPD exacerbations. Comparator and reference safety profiles were similar.
| Original language | English |
|---|---|
| Article number | e0191404 |
| Journal | PloS ONE |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 24 Jan 2018 |
Bibliographical note
This study was sponsored and funded by Teva Branded Pharmaceutical Products, R&D, Inc (Frazer, PA). The study was designed by academic investigators and by representatives of the sponsor, Teva Branded Pharmaceutical Products, R&D, Inc. Statistical analysis was completed by investigator VT. All authors contributed to the interpretation of data and writing or critically reviewing and revising the manuscript. All authors had access to the data and take complete responsibility for the integrity of the data and accuracy of the data analysis. The corresponding author had full access to all of the data and had final responsibility to submit for publication. This manuscript was prepared according to the International Society for Medical Publication Professionals’ Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.Data Availability: All relevant data are within the paper, and unmatched data for all outcomes is provided in the Supporting Information files. The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink (www.cprd.com) and the UK Optimum Patient Care Research Database (www.opcrd.co.uk). The authors do not have permission to give public access to these databases; however, researchers may request access for their own purposes. The CPRD has broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymized research data (Research Ethics Committee reference: 15/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) Committee—the independent scientific advisory committee for the OPCRD, commissioned by the Respiratory Effectiveness Group—and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP/SDPP/7645).