应用ICS-福莫特罗或ICS-沙美特罗维持治疗的哮喘患者中按需福莫特罗的安全性和有效性
2023/04/21
摘要
背景：根据需要，建议哮喘患者使用低剂量吸入皮质类固醇（ICS）-福莫特罗缓解剂，维持ICS福莫特罗。临床医生经常询问ICS-福莫特罗缓解剂是否可以与其他维持性ICS长效β2-激动剂（LABA）一起使用。
目的：评估RELEF研究中服用ICS-福莫特罗或ICS沙美特罗维持治疗患者所需福莫特罗的安全性和有效性。
方法：RELIEF（SD-037-0699）是一项为期6个月的开放标签研究，将18124名哮喘患者随机分为4.5μg福莫特罗或200μg沙丁胺醇，再加上维持治疗。这项事后分析包括使用ICS福莫特罗或ICS沙美特罗维持治疗的患者（n=5436）。主要安全性结果是严重不良事件（SAE）和/或导致停药的不良事件（DAE）的复合结果；主要有效性结果是首次发作的时间。
结果：对于两个维持组和两个缓解组，相似数量的患者具有≥1个SAE和/或DAE。在服用维持性ICS-沙美特罗而非ICS-福莫特罗的患者中，与需要的沙丁胺醇相比，需要的福莫特罗出现的非哮喘相关和非严重DAE明显更多（分别为p=0.0066和p=0.0034）。在服用ICS-福莫特罗维持治疗的患者中，与使用沙丁胺醇相比，使用所需福莫特罗的首次发作风险显著降低（HR 0.82；95%CI 0.70，0.95；p=0.007）。在服用ICS-沙美特罗维持治疗患者中，治疗组之间的首次发作时间没有显著差异（HR 0.95；95%CI 0.84，1.06；p=0.035）。
结论：在ICS-福莫特罗维持治疗中，而非ICS-沙美特罗，按需福莫特罗比按需沙丁胺醇显著降低了哮喘发作风险。使用ICS-沙美特罗维持治疗加上按需福莫特罗，可以看到更多的DAE。需要进一步的研究来评估这是否与所需的ICS-福莫特罗组合有关。
Safety and effectiveness of as-needed formoterol in asthma patients taking ICS-formoterol or ICS-salmeterol maintenance therapy
Helen K Reddel, Guy Brusselle, Rosa Lamarca, Per Gustafson, Gary P Anderson, Carin Jorup
Abstract
Background: As-needed low-dose inhaled corticosteroid (ICS)-formoterol reliever is recommended in asthma patients prescribed maintenance ICS-formoterol. Clinicians often ask whether ICS-formoterol reliever can be used with other maintenance ICS-long-acting β2-agonists (LABAs).
Objective: To evaluate safety and effectiveness of as-needed formoterol in patients taking maintenance ICS-formoterol or ICS-salmeterol from the RELIEF study.
Methods: RELIEF (SD-037-0699) was a 6-month, open-label study that randomized 18,124 patients with asthma to as-needed formoterol 4.5μg or salbutamol 200μg on top of maintenance therapy. This post hoc analysis included patients on maintenance ICS-formoterol or ICS-salmeterol (n=5,436). The primary safety outcome was a composite of serious adverse events (SAEs) and/or adverse events leading to discontinuation (DAEs); the primary effectiveness outcome was time-to-first exacerbation.
Results: For both maintenance groups and both relievers, similar numbers of patients had ≥1 SAE and/or DAE. In patients taking maintenance ICS-salmeterol, but not ICS-formoterol, significantly more non-asthma-related and non-serious DAEs occurred with as-needed formoterol versus as-needed salbutamol (p=0.0066 and p=0.0034, respectively). In patients taking maintenance ICS-formoterol, there was a significantly lower risk in time-to-first exacerbation with as-needed formoterol versus as-needed salbutamol (HR 0.82; 95% CI 0.70, 0.95; p=0.007). In patients taking ICS-salmeterol maintenance, time-to-first exacerbation was not significantly different between treatment arms (HR 0.95; 95% CI 0.84, 1.06; p=0.35).
Conclusions: As-needed formoterol significantly reduced exacerbation risk compared with as-needed salbutamol when added to maintenance ICS-formoterol, but not to maintenance ICS-salmeterol. More DAEs were seen with ICS-salmeterol maintenance therapy plus as-needed formoterol. Further research is needed to assess whether this is relevant to as-needed combination ICS-formoterol.
背景：根据需要，建议哮喘患者使用低剂量吸入皮质类固醇（ICS）-福莫特罗缓解剂，维持ICS福莫特罗。临床医生经常询问ICS-福莫特罗缓解剂是否可以与其他维持性ICS长效β2-激动剂（LABA）一起使用。
目的：评估RELEF研究中服用ICS-福莫特罗或ICS沙美特罗维持治疗患者所需福莫特罗的安全性和有效性。
方法：RELIEF（SD-037-0699）是一项为期6个月的开放标签研究，将18124名哮喘患者随机分为4.5μg福莫特罗或200μg沙丁胺醇，再加上维持治疗。这项事后分析包括使用ICS福莫特罗或ICS沙美特罗维持治疗的患者（n=5436）。主要安全性结果是严重不良事件（SAE）和/或导致停药的不良事件（DAE）的复合结果；主要有效性结果是首次发作的时间。
结果：对于两个维持组和两个缓解组，相似数量的患者具有≥1个SAE和/或DAE。在服用维持性ICS-沙美特罗而非ICS-福莫特罗的患者中，与需要的沙丁胺醇相比，需要的福莫特罗出现的非哮喘相关和非严重DAE明显更多（分别为p=0.0066和p=0.0034）。在服用ICS-福莫特罗维持治疗的患者中，与使用沙丁胺醇相比，使用所需福莫特罗的首次发作风险显著降低（HR 0.82；95%CI 0.70，0.95；p=0.007）。在服用ICS-沙美特罗维持治疗患者中，治疗组之间的首次发作时间没有显著差异（HR 0.95；95%CI 0.84，1.06；p=0.035）。
结论：在ICS-福莫特罗维持治疗中，而非ICS-沙美特罗，按需福莫特罗比按需沙丁胺醇显著降低了哮喘发作风险。使用ICS-沙美特罗维持治疗加上按需福莫特罗，可以看到更多的DAE。需要进一步的研究来评估这是否与所需的ICS-福莫特罗组合有关。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol Pract. 2023 Apr 11;S2213-2198(23)00398-7. doi: 10.1016/j.jaip.2023.03.046.)
(J Allergy Clin Immunol Pract. 2023 Apr 11;S2213-2198(23)00398-7. doi: 10.1016/j.jaip.2023.03.046.)
Safety and effectiveness of as-needed formoterol in asthma patients taking ICS-formoterol or ICS-salmeterol maintenance therapy
Helen K Reddel, Guy Brusselle, Rosa Lamarca, Per Gustafson, Gary P Anderson, Carin Jorup
Abstract
Background: As-needed low-dose inhaled corticosteroid (ICS)-formoterol reliever is recommended in asthma patients prescribed maintenance ICS-formoterol. Clinicians often ask whether ICS-formoterol reliever can be used with other maintenance ICS-long-acting β2-agonists (LABAs).
Objective: To evaluate safety and effectiveness of as-needed formoterol in patients taking maintenance ICS-formoterol or ICS-salmeterol from the RELIEF study.
Methods: RELIEF (SD-037-0699) was a 6-month, open-label study that randomized 18,124 patients with asthma to as-needed formoterol 4.5μg or salbutamol 200μg on top of maintenance therapy. This post hoc analysis included patients on maintenance ICS-formoterol or ICS-salmeterol (n=5,436). The primary safety outcome was a composite of serious adverse events (SAEs) and/or adverse events leading to discontinuation (DAEs); the primary effectiveness outcome was time-to-first exacerbation.
Results: For both maintenance groups and both relievers, similar numbers of patients had ≥1 SAE and/or DAE. In patients taking maintenance ICS-salmeterol, but not ICS-formoterol, significantly more non-asthma-related and non-serious DAEs occurred with as-needed formoterol versus as-needed salbutamol (p=0.0066 and p=0.0034, respectively). In patients taking maintenance ICS-formoterol, there was a significantly lower risk in time-to-first exacerbation with as-needed formoterol versus as-needed salbutamol (HR 0.82; 95% CI 0.70, 0.95; p=0.007). In patients taking ICS-salmeterol maintenance, time-to-first exacerbation was not significantly different between treatment arms (HR 0.95; 95% CI 0.84, 1.06; p=0.35).
Conclusions: As-needed formoterol significantly reduced exacerbation risk compared with as-needed salbutamol when added to maintenance ICS-formoterol, but not to maintenance ICS-salmeterol. More DAEs were seen with ICS-salmeterol maintenance therapy plus as-needed formoterol. Further research is needed to assess whether this is relevant to as-needed combination ICS-formoterol.
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