Safety of as-needed budesonide-formoterol in mild asthma: data from the two Phase III SYGMA studies

J. Mark FitzGerald*, Paul M. O’Byrne, Eric D. Bateman, Peter J. Barnes, Jinping Zheng, Stefan Ivanov, Rosa Lamarca, Ulrika Larsdotter, Ulrika Emerath, Gerreke Jansen, Margareta Puu, Vijay K. T. Alagappan, Filip Surmont, Helen K. Reddel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)
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Abstract

Introduction: Budesonide-formoterol taken as needed is an emerging treatment for mild asthma. Objective: We used data from the SYGMA studies to assess the safety of As-needed budesonide-formoterol compared with As-needed terbutaline and compared with maintenance budesonide. Methods: SYGMA 1 and 2 were 52-week, double-blind, parallel-group studies in patients aged ≥ 12 years with physician-assessed mild asthma. Patients were randomized to As-needed budesonide-formoterol 200/6 μg, twice-daily budesonide 200 μg as maintenance plus As-needed terbutaline 0.5 mg, and As-needed terbutaline 0.5 mg (SYGMA 1 only). Adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs (DAEs), and study-defined asthma-related discontinuations from corresponding treatment groups in both studies were pooled. SYGMA 1 data were used for comparisons with As-needed terbutaline alone. Results: The pooled analysis included 3366 patients in the As-needed budesonide-formoterol group and 3369 in the budesonide maintenance group, with AEs in 40.8% and 42.5% of patients, respectively. Common AEs included viral upper respiratory tract infection (viral URTI) and URTI. SAE, DAE, and asthma-related discontinuation rates were similar with As-needed budesonide-formoterol and maintenance budesonide. Potential local and systemic corticosteroid class effects were reported in ≤ 1% of patients for each budesonide-containing regimen. In SYGMA 1, AEs were more common in the As-needed terbutaline (n = 1277) than As-needed budesonide-formoterol (n = 1277) groups (42.7 vs. 38.0%), as were DAEs (2.9 vs. 0.8%) and asthma-related discontinuations (1.6 vs. 0.3%). Conclusions: Budesonide-formoterol anti-inflammatory reliever therapy is generally well-tolerated in patients with mild asthma and has a safety profile similar to that of daily budesonide. No new safety signals were identified. ClinicalTrial.gov Identifiers: NCT02149199 (SYGMA 1) and NCT02224157 (SYGMA 2).

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalDrug Safety
Volume44
Issue number4
DOIs
Publication statusPublished - Apr 2021
Externally publishedYes

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Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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