PMID- 29364929 OWN - NLM STAT- MEDLINE DCOM- 20180226 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 1 DP - 2018 TI - Real-life effectiveness and safety of salbutamol Steri-Neb vs. Ventolin Nebules(R) for exacerbations in patients with COPD: Historical cohort study. PG - e0191404 LID - 10.1371/journal.pone.0191404 [doi] LID - e0191404 AB - INTRODUCTION: Ventolin Nebules(R) (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting beta2-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. FAU - Price, David B AU - Price DB AUID- ORCID: 0000-0002-9728-9992 AD - Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom. AD - Observational & Pragmatic Research Institute, Singapore, Singapore. FAU - Gefen, Eran AU - Gefen E AD - Teva Pharmaceuticals, Petach Tikva, Israel. FAU - Gopalan, Gokul AU - Gopalan G AD - Teva Pharmaceuticals, Frazer, Pennsylvania, United States of America. FAU - McDonald, Rosie AU - McDonald R AD - Observational & Pragmatic Research Institute, Singapore, Singapore. FAU - Thomas, Vicky AU - Thomas V AD - Observational & Pragmatic Research Institute, Singapore, Singapore. FAU - Ming, Simon Wan Yau AU - Ming SWY AD - Observational & Pragmatic Research Institute, Singapore, Singapore. FAU - Davis, Emily AU - Davis E AD - Observational & Pragmatic Research Institute, Singapore, Singapore. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180124 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adrenergic beta-2 Receptor Agonists) RN - 0 (Bronchodilator Agents) RN - QF8SVZ843E (Albuterol) SB - IM MH - Administration, Inhalation MH - Adrenergic beta-2 Receptor Agonists/*administration & dosage/adverse effects MH - Adult MH - Aged MH - Aged, 80 and over MH - Albuterol/*administration & dosage/adverse effects MH - Bronchodilator Agents/*administration & dosage/adverse effects MH - Cohort Studies MH - Disease Progression MH - Female MH - Humans MH - Male MH - Middle Aged MH - Nebulizers and Vaporizers MH - Pulmonary Disease, Chronic Obstructive/*drug therapy/physiopathology MH - Treatment Outcome PMC - PMC5783390 COIS- Competing Interests: DBP has board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Mylan, Mundipharma, Napp, Novartis, Pfizer, Respiratory Effectiveness Group, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva; payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, and Teva Pharmaceuticals; payment for manuscript preparation from Mundipharma and Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from Aerocrine, AstraZeneca, Boehringer Ingelheim, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals; funding for patient enrollment or completion of research from Chiesi, Novartis, Teva Pharmaceuticals, and Zentiva; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia, Singapore, and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment. EG is an employee of Teva Pharmaceuticals. GG was an employee of Teva Pharmaceuticals during the time of the study. RM and SWYM are employees of Observational and Pragmatic Research Institute Pte Ltd, which conducted this study and has conducted paid research in respiratory disease on behalf of the following other organizations in the past 5 years: Aerocrine, AKL Research and Development Ltd, Almirall, AstraZeneca, British Lung Foundation, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Orion, Respiratory Effectiveness Group, Takeda, Teva Pharmaceuticals, and Zentiva, a Sanofi company. ED and VT were employed by Observational and Pragmatic Research Institute Pte Ltd, at the time of the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2018/01/25 06:00 MHDA- 2018/02/27 06:00 PMCR- 2018/01/24 CRDT- 2018/01/25 06:00 PHST- 2017/08/22 00:00 [received] PHST- 2018/01/04 00:00 [accepted] PHST- 2018/01/25 06:00 [entrez] PHST- 2018/01/25 06:00 [pubmed] PHST- 2018/02/27 06:00 [medline] PHST- 2018/01/24 00:00 [pmc-release] AID - PONE-D-17-30986 [pii] AID - 10.1371/journal.pone.0191404 [doi] PST - epublish SO - PLoS One. 2018 Jan 24;13(1):e0191404. doi: 10.1371/journal.pone.0191404. eCollection 2018.