Abstract
Objective
The objective of this study was to determine whether the effectiveness of budesonide comparator is non-inferior to budesonide reference in the prevention of asthma exacerbations. Asthma-related hospitalizations and safety were also examined.
Methods
This study used a matched, historic cohort design. Data were drawn from the Clinformatics™ Data Mart US claims database and included a 1-year baseline, starting 1 year before the index prescription date, and a 1-year outcome period. Patients received budesonide comparator or reference treatment. The primary outcome was the rate of asthma exacerbations. Non-inferiority for budesonide comparator vs budesonide reference was established if the 95% confidence interval (CI) upper limit of mean difference in proportions between treatments was <15%. Secondary outcomes examined rate of asthma-related hospitalizations and adverse events (AEs).
Results
The budesonide comparator and reference-matched cohorts each included 3109 patients. The adjusted upper 95% CI for the difference in proportions of patients experiencing asthma exacerbations was 0.035 (3.5%), demonstrating non-inferiority. Cohorts did not significantly differ in the rate of asthma exacerbations (adjusted rate ratio [RR]=1.04, 95% CI: 0.95–1.14) or rate of asthma-related hospitalizations (adjusted RR=1.10, 95% CI: 0.99–1.24) after adjusting for baseline confounders. No asthma exacerbations occurred during the outcome period in 72.9% of budesonide comparator patients and 71.8% of budesonide reference patients. No asthma-related hospitalizations occurred in 77.9% of patients in the budesonide comparator cohort and 79.0% of patients in the budesonide reference cohort. The most frequent AEs were throat irritation (≤0.4% of patients) and hoarseness/dysphonia (0.02% of patients). AEs did not significantly differ between treatment cohorts.
Conclusion
In this real-life study, non-inferiority of the budesonide comparator vs reference was met for the primary end point of asthma exacerbation rates. Asthma-related hospitalization and AE rates did not differ between the two treatment cohorts. The budesonide comparator is an effective and safe treatment alternative for asthma exacerbations.
Acknowledgments
The authors thank Robert Rhoades, PhD, and Lynanne McGuire, PhD, of MedVal Scientific Information Services, LLC, for providing medical writing and editorial assistance and Priyanka Raju Konduru of Observational and Pragmatic Research Institute Pte Ltd (OPRI) for assistance with data extraction. This manuscript was prepared according to the International Society for Medical Publication Professionals’ Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3. Medical writing assistance was provided by MedVal Scientific Information Services, LLC, and was funded by Teva Branded Pharmaceutical Products R&D, Inc. (Frazer, PA). Teva provided a full review of the article. Funding for this study was provided by Teva Branded Pharmaceutical Products R&D, Inc. (Frazer, PA).
Author contributions
DBP, CM, GG, RM, VT, and SWYM contributed toward study concept and design. All authors involved in acquisition, analysis, or interpretation of data. All authors participated in drafting of manuscript. All authors made critical revisions of manuscript for important intellectual content. VT contributed toward statistical analysis. All authors gave the final approval of manuscript.
Disclosure
CM, RM, and VT were employed by OPRI at the time of the study; CM was a project leader. SWYM is an employee of OPRI. OPRI 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, REG, Takeda, Teva Pharmaceuticals, and Zentiva, a Sanofi company. EG is an employee of Teva Pharmaceuticals. GG was an employee of Teva Pharmaceuticals during the time of the study. DBP has board membership with Aerocrine, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Mundipharma, Napp, Novartis, and Teva Pharmaceuticals; consultancy agreements with Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Meda, Mundipharma, Napp, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through OPRI) from Aerocrine, AKL Research and Development Ltd, AstraZeneca, Boehringer Ingelheim, British Lung Foundation, Chiesi, Meda, Mundipharma, Napp, Novartis, Pfizer, REG, Takeda, Teva Pharmaceuticals, Theravance, UK National Health Service, Zentiva; payment for lectures/speaking engagements from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck, Mundipharma, Novartis, Pfizer, Skyepharma, Takeda, 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 enrolment 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, UK, and 74% of OPRI, Singapore; and is a peer reviewer for grant committees of the Efficacy and Mechanism Evaluation program, Health Technology Assessment, and Medical Research Council. DBP currently serves as Editor-in-Chief for Pragmatic and Observational Research. To be fully transparent and conform with COPE guidelines addressing an editor as author in own journal, the following procedures were implemented: 1) the addressee for the manuscript submission cover letter was journal editorial board member Professor Arora; 2) the manuscript peer review process was handled by journal editorial board member Dr John Haughney and was independent of the editor-in-chief (recognizing that it would not be possible to completely remove bias); and 3) the paper was sent out for review without any names included. The authors report no other conflicts of interest in this work.