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, 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

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).

Conflict of interest statement

Paul M. O’Byrne received grants and personal fees from AstraZeneca during the conduct of the study; grants and personal fees from GlaxoSmithKline; personal fees from Menarini; and grants from MedImmune, AllerGen NCE, Genentech, Novartis, Merck, and Bayer outside of the submitted work. J. Mark FitzGerald received grants and personal fees from AstraZeneca during the conduct of the study; grants paid to his institution from the Canadian Institute for Health Research, the National Institutes for Health, AllerGen NCE, AstraZeneca, Novartis, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi-Aventis outside the submitted work; and personal fees from GlaxoSmithKline, Novartis, Sanofi Regeneron, and Boehringer Ingelheim; and is a Member of the Global Initiative for Asthma (GINA) Science Committee and the GINA Board. Eric D. Bateman has received personal fees from AstraZeneca, ALK, Boehringer Ingelheim, Menarini, Novartis, Orion, Regeneron, and Sanofi-Genzyme and is a member of the GINA Science Committee and the GINA Board. Peter J. Barnes received grants and personal fees from AstraZeneca during the conduct of the study. Jinping Zheng has received personal fees from AstraZeneca. Stefan Ivanov, Rosa Lamarca, Ulrika Larsdotter, Ulrika Emerath, Gerreke Jansen, Margareta Puu, Vijay Alagappan, and Filip Surmont are all employees of AstraZeneca. Helen K. Reddel received personal fees and non-financial support from AstraZeneca during the conduct of the study; grants, personal fees, and non-financial support from AstraZeneca and GlaxoSmithKline; grants and personal fees from Novartis; and personal fees from Sanofi-Genzyme, Merck, Boehringer Ingelheim, Mundipharma, Chiesi, and TEVA outside of the submitted work; and is chair of the GINA Scientific Committee and a member of the GINA board.

Figures

Fig. 1
Fig. 1
Proportion of patients with high As-needed use of budesonide-formoterol or terbutaline (in the As-needed terbutaline group or budesonide maintenance group) on at least 1 day during the study in a SYGMA 1 [7] and b SYGMA 2 [5]. Data are from the full analysis sets in both studies. The number of inhalations in a day is the sum of day- and night-time As-needed inhalations

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Source: PubMed

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