Positioning As-needed Budesonide–Formoterol for Mild Asthma: Effect of Prestudy Treatment in Pooled Analysis of SYGMA 1 and 2 Academic Article uri icon

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  • RATIONALE: The SYGMA studies evaluated the efficacy and safety of as-needed budesonide-formoterol (BUD-FORM) in patients whose asthma was uncontrolled on as-needed inhaled short-acting bronchodilators (Subgroup 1) or controlled on inhaled corticosteroid (ICS) or leukotriene receptor antagonist (Subgroup 2). OBJECTIVE: To assess the influence of pre-study treatment in a post hoc analysis of the SYGMA studies. METHODS: In the SYGMA 1 (NCT022149199) and SYGMA 2 (NCT02224157) 52-week, double-blind, randomized, parallel-group studies, 6,735 mild asthma patients were randomized to as-needed BUD-FORM, low-dose budesonide + as-needed terbutaline (BUD maintenance), or as-needed terbutaline (SYGMA 1 only). Exacerbation rates and changes in symptom control and lung function were compared between treatments for both Subgroups. RESULTS: In a pooled analysis of SYGMA 1 and 2, annual severe exacerbation rate was significantly lower in Subgroup 1 with as-needed BUD-FORM (0.08 [95% CI 0.06, 0.10]) vs BUD maintenance (0.10 [0.09, 0.13]) (rate ratio [RR] 0.74 [0.56, 0.98], p=0.03), and was similar in Subgroup 2 with BUD-FORM (0.12 [0.10, 0.14]) and BUD maintenance (0.10 [0.09, 0.13]) (RR 1.10 [0.86, 1.41], p=0.44). In SYGMA 1, the annual severe exacerbation rate was significantly lower in both Subgroups with as-needed BUD-FORM vs as-needed terbutaline (Subgroup 1: RR 0.34 [0.20, 0.58], p<0.001; Subgroup 2: RR 0.37 [0.25, 0.54], p<0.001). NNT to prevent one severe exacerbation with as-needed BUD-FORM and BUD maintenance vs as-needed terbutaline was 20 and 34 in Subgroup 1 and 13 and 12 in Subgroup 2, respectively. CONCLUSIONS: These findings suggest that, for patients with mild asthma currently taking SABA alone, as-needed low-dose ICS-formoterol should be preferred over maintenance ICS as initial controller treatment. For patients whose asthma is controlled on maintenance low-dose ICS, as-needed BUD-FORM is an alternative to maintenance ICS without the need for daily treatment, and both of these options are safer than switching to SABA-only treatment.


  • O'Byrne, Paul
  • Bateman, Eric D
  • O’Byrne, Paul M
  • FitzGerald, J Mark
  • Barnes, Peter J
  • Zheng, Jinping
  • Lamarca, Rosa
  • Puu, Margareta
  • Parikh, Himanshu
  • Alagappan, Vijay
  • Reddel, Helen K

publication date

  • December 2021