Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Firestone Institute for Respiratory Health, St. Joseph's Healthcare and Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Ann Am Thorac Soc. 2021 Dec;18(12):2007-2017. doi: 10.1513/AnnalsATS.202011-1386OC.
The SYGMA (Symbicort Given as Needed in Mild Asthma) studies evaluated the efficacy and safety of as-needed budesonide (BUD)-formoterol (FORM) in patients whose asthma was uncontrolled on as-needed inhaled short-acting bronchodilators (subgroup 1) or controlled on inhaled corticosteroids (ICS) or leukotriene receptor antagonists (subgroup 2). To assess the influence of prestudy treatment in a analysis of the SYGMA studies. In the SYGMA 1 (NCT022149199) and SYGMA 2 (NCT02224157) 52-week, double-blind, randomized, parallel-group studies, 6,735 patients with mild asthma were randomized to as-needed BUD-FORM, low-dose BUD + as-needed terbutaline (BUD maintenance), or as-needed terbutaline (SYGMA 1 only). Exacerbation rates and changes in symptom control and lung function were compared among treatments for both subgroups. In a pooled analysis of SYGMA 1 and 2, the annual severe exacerbation rate in subgroup 1 was significantly lower with as-needed BUD-FORM (0.08 [95% confidence interval (CI), 0.06-0.10]) than with BUD maintenance (0.10 [95% CI, 0.09-0.13]) (rate ratio [RR], 0.74 [95% CI, 0.56-0.98]; = 0.03), and similar results were shown in subgroup 2 with BUD-FORM (0.12 [95% CI, 0.10-0.14]) and BUD maintenance (0.10 [95% CI, 0.09-0.13]) (RR, 1.10 [95% CI, 0.86-1.41]; = 0.44). In SYGMA 1, the annual severe exacerbation rate in both subgroups was significantly lower with as-needed BUD-FORM than with as-needed terbutaline (subgroup 1: RR, 0.34 [95% CI, 0.20-0.58]; < 0.001; subgroup 2: RR, 0.37 [95% CI, 0.25-0.54]; < 0.001). The number needed to treat to prevent one severe exacerbation with as-needed BUD-FORM and BUD maintenance versus as-needed terbutaline were 20 and 34 in subgroup 1 and 13 and 12 in subgroup 2, respectively. These findings suggest that, for patients with mild asthma currently receiving short-acting β-agonists alone, as-needed low-dose ICS-FORM 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 short-acting β-agonist-only treatment.
SYGMA（按需给予布地奈德/福莫特罗治疗轻度哮喘）研究评估了按需给予布地奈德（BUD）-福莫特罗（FORM）在接受按需吸入短效支气管扩张剂治疗仍未控制哮喘（亚组 1）或接受吸入皮质激素（ICS）或白三烯受体拮抗剂（LTRA）治疗控制良好的哮喘患者中的疗效和安全性。在 SYGMA 研究的分析中评估了预研究治疗的影响。在 SYGMA 1（NCT022149199）和 SYGMA 2（NCT02224157）52 周、双盲、随机、平行分组研究中，6735 例轻度哮喘患者被随机分配接受按需给予 BUD-FORM、低剂量 BUD+按需给予特布他林（BUD 维持治疗）或按需给予特布他林（仅 SYGMA 1）。在两个亚组中比较了治疗之间的加重率以及症状控制和肺功能的变化。在 SYGMA 1 和 2 的汇总分析中，亚组 1 的年严重加重率显著低于 BUD 维持治疗（0.10 [95%置信区间（CI），0.09-0.13]）（RR，0.74 [95% CI，0.56-0.98]； = 0.03），而在亚组 2 中 BUD-FORM（0.12 [95% CI，0.10-0.14]）和 BUD 维持治疗（0.10 [95% CI，0.09-0.13]）（RR，1.10 [95% CI，0.86-1.41]； = 0.44）也显示出相似的结果。在 SYGMA 1 中，两个亚组的年严重加重率均显著低于按需给予 BUD-FORM（RR，0.34 [95% CI，0.20-0.58]； < 0.001；亚组 2：RR，0.37 [95% CI，0.25-0.54]； < 0.001）。与按需给予特布他林相比，按需给予 BUD-FORM 和 BUD 维持治疗预防一次严重加重的需要治疗人数分别为 20 和 34（亚组 1）和 13 和 12（亚组 2）。这些发现表明，对于目前单独接受短效 β-激动剂治疗的轻度哮喘患者，应优先选择低剂量 ICS-FORM 按需治疗，而不是维持 ICS 作为初始控制治疗。对于接受低剂量 ICS 维持治疗的哮喘控制良好的患者，按需给予 BUD-FORM 是替代维持 ICS 的选择，而无需每日治疗，且这两种选择均比切换为仅使用短效 β-激动剂治疗更安全。
