布地奈德-福莫特罗对比特布他林缓解剂用于维持ICS的成人哮喘：一项IV期试验
2026/03/30
摘要
背景：目前，支持维持性吸入性皮质类固醇对2型气道炎症影响的循证证据依然有限，且相关随机对照试验（RCT）数据较为缺乏。因此，基于吸入性类固醇-福莫特罗缓解剂方案的临床疗效和有效性尚不明确。本研究旨在比较轻中度哮喘患者中，维持性吸入性皮质类固醇联合布地奈德-福莫特罗缓解剂或特布他林缓解剂的临床疗效与安全性。
研究方法：本研究是一项开放标签、平行组、随机对照的IV期临床试验，在惠灵顿医院及新西兰两家社区基层初级保健机构开展。符合条件的参与者年龄在16至75岁之间，有医生诊断的哮喘并在全科医生处注册。参与者既往仅使用缓解疗法，或使用维持性吸入性类固醇联合短效β2受体激动剂缓解疗法。参与者在入组前12周内平均每周需使用缓解剂两次或以上，并在筛查时存在气道炎症的证据（呼出气一氧化氮[FeNO] ≥ 25 ppb）。按照计算机生成的随机序列将参与者进行1:1随机分配到区组大小为4和6的组别中，接受布地奈德-福莫特罗（布地奈德200 μg/福莫特罗6 μg）缓解剂或特布他林（250 μg）缓解剂，随机化分层因素包括地区、基线吸入性皮质类固醇维持剂量以及过去12个月内是否有重度哮喘急性发作史。所有参与者均接受维持剂量布地奈德（200 μg）。在为期26周的治疗期间，参与者在第0周（筛查与随机分组）、第13周和第26周进行随访。主要结局指标为第26周的FeNO值，在意向性治疗（ITT）人群中进行评估。该试验已在澳大利亚新西兰临床试验注册中心注册（注册号：ACTRN12622001304729，已完成）。
研究结果：在2023年3月28日至2024年8月27日期间，共评估290名参与者的合格性，其中109人不符合入组标准，最终181名参与者被随机分配至布地奈德-福莫特罗组（n=93）或特布他林缓解组（n=88；ITT人群）。参与者的平均年龄为33.91岁（标准差为15.54岁）。181名参与者中，女性119人（66%），男性62人（34%）。布地奈德-福莫特罗组FeNO均值为62.18 ppb（标准差为1.86），第26周时为39.65 ppb（标准差为2.12）；特布他林组FeNO均值为68.03 ppb（标准差为1.97），第26周时为52.98 ppb（标准差为2.27）。与特布他林缓解治疗相比，布地奈德-福莫特罗缓解治疗在第26周时均数FeNO降低18.50%（95% CI 2.72–31.73；p = 0.024）。布地奈德-福莫特罗组93名参与者中有77人（83%）发生不良事件，特布他林组88人中有69人（78%）至少发生一次不良事件（相对风险为1.06 [95% CI 0.91–1.22]；p = 0.46）。研究中未报告死亡病例。
结果解读：在接受维持性吸入性类固醇治疗的成人哮喘患者中，布地奈德-福莫特罗缓解剂相较于特布他林缓解剂可有效降低FeNO水平。布地奈德-福莫特罗缓解剂是接受维持性吸入性类固醇治疗的成人哮喘患者替代短效β2受体激动剂缓解疗法的安全且有效的选择。
Background: Recommendations for the use of inhaled corticosteroid-formoterol reliever-based regimens are limited by the absence of randomised controlled trials (RCTs) in patients with asthma using maintenance inhaled corticosteroids, and scarce evidence for the effect on type 2 airway inflammation. We aimed to examine the clinical efficacy and safety of maintenance inhaled corticosteroids plus budesonide-formoterol reliever or terbutaline reliever in patients with mild-to-moderate asthma.
Methods: This open-label, parallel-group, randomised, controlled, phase 4 trial was conducted at Wellington Hospital and two community-based primary care facilities in New Zealand. Eligible participants were aged 16-75 years, had a self-reported doctor's diagnosis of asthma, were using reliever only therapy or maintenance inhaled corticosteroids with short-acting β2-agonist reliever therapy, and were registered with a general practitioner. Participants had to have reported mean reliever use on two or more occasions per week in the 12 weeks before enrolment and had evidence of airway inflammation (FeNO ≥25 parts per billion [ppb]) at screening. Participants were randomly assigned (1:1) to budesonide-formoterol (budesonide 200 μg and formoterol 6 μg) reliever or terbutaline 250 μg reliever therapy using a computer-generated sequence in block sizes of four and six, stratified by region, baseline inhaled corticosteroids maintenance dose, and history of severe asthma exacerbation in the previous 12 months. All participants received maintenance budesonide 200 μg. During a 26-week treatment period, participants attended visits at weeks 0 (screening and randomisation), 13, and 26. The primary outcome was FeNO at week 26, measured in the intention-to-treat (ITT) population. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12622001304729 (completed).
Findings: Between March 28, 2023, and Aug 27, 2024, 290 participants were assessed for eligibility, 109 were ineligible, and 181 were randomly assigned to budesonide-formoterol (n=93) or terbutaline reliever therapy (n=88; ITT population). Participants had a mean age of 33·91 years (SD 15·54). 119 (66%) of 181 participants were female and 62 (34%) were male. Geometric mean FeNO was 62·18 ppb (SD 1·86) at baseline and 39·65 ppb (2·12) at week 26, for the budesonide-formoterol group and 68·03 ppb (1·97) at baseline and 52·98 ppb (2·27) at week 26 for the terbutaline group. Budesonide-formoterol reliever therapy resulted in a mean reduction in geometric mean FeNO of 18·50% (95% CI 2·72-31·73; p=0·024) at week 26 compared with terbutaline reliever therapy. 77 (83%) of 93 participants in the budesonide-formoterol group versus 69 (78%) of 88 in the terbutaline group had at least one adverse event (relative risk 1·06 [95% CI 0·91-1·22]; p=0·46). There were no deaths in the study.
Interpretation: Budesonide-formoterol reliever therapy resulted in a reduction in FeNO compared with terbutaline reliever in adults with asthma using maintenance inhaled corticosteroids. Budesonide-formoterol reliever is a safe and effective alternative to short-acting β2-agonist reliever therapy for adults using maintenance inhaled corticosteroids.
背景：目前，支持维持性吸入性皮质类固醇对2型气道炎症影响的循证证据依然有限，且相关随机对照试验（RCT）数据较为缺乏。因此，基于吸入性类固醇-福莫特罗缓解剂方案的临床疗效和有效性尚不明确。本研究旨在比较轻中度哮喘患者中，维持性吸入性皮质类固醇联合布地奈德-福莫特罗缓解剂或特布他林缓解剂的临床疗效与安全性。
研究方法：本研究是一项开放标签、平行组、随机对照的IV期临床试验，在惠灵顿医院及新西兰两家社区基层初级保健机构开展。符合条件的参与者年龄在16至75岁之间，有医生诊断的哮喘并在全科医生处注册。参与者既往仅使用缓解疗法，或使用维持性吸入性类固醇联合短效β2受体激动剂缓解疗法。参与者在入组前12周内平均每周需使用缓解剂两次或以上，并在筛查时存在气道炎症的证据（呼出气一氧化氮[FeNO] ≥ 25 ppb）。按照计算机生成的随机序列将参与者进行1:1随机分配到区组大小为4和6的组别中，接受布地奈德-福莫特罗（布地奈德200 μg/福莫特罗6 μg）缓解剂或特布他林（250 μg）缓解剂，随机化分层因素包括地区、基线吸入性皮质类固醇维持剂量以及过去12个月内是否有重度哮喘急性发作史。所有参与者均接受维持剂量布地奈德（200 μg）。在为期26周的治疗期间，参与者在第0周（筛查与随机分组）、第13周和第26周进行随访。主要结局指标为第26周的FeNO值，在意向性治疗（ITT）人群中进行评估。该试验已在澳大利亚新西兰临床试验注册中心注册（注册号：ACTRN12622001304729，已完成）。
研究结果：在2023年3月28日至2024年8月27日期间，共评估290名参与者的合格性，其中109人不符合入组标准，最终181名参与者被随机分配至布地奈德-福莫特罗组（n=93）或特布他林缓解组（n=88；ITT人群）。参与者的平均年龄为33.91岁（标准差为15.54岁）。181名参与者中，女性119人（66%），男性62人（34%）。布地奈德-福莫特罗组FeNO均值为62.18 ppb（标准差为1.86），第26周时为39.65 ppb（标准差为2.12）；特布他林组FeNO均值为68.03 ppb（标准差为1.97），第26周时为52.98 ppb（标准差为2.27）。与特布他林缓解治疗相比，布地奈德-福莫特罗缓解治疗在第26周时均数FeNO降低18.50%（95% CI 2.72–31.73；p = 0.024）。布地奈德-福莫特罗组93名参与者中有77人（83%）发生不良事件，特布他林组88人中有69人（78%）至少发生一次不良事件（相对风险为1.06 [95% CI 0.91–1.22]；p = 0.46）。研究中未报告死亡病例。
结果解读：在接受维持性吸入性类固醇治疗的成人哮喘患者中，布地奈德-福莫特罗缓解剂相较于特布他林缓解剂可有效降低FeNO水平。布地奈德-福莫特罗缓解剂是接受维持性吸入性类固醇治疗的成人哮喘患者替代短效β2受体激动剂缓解疗法的安全且有效的选择。
（南方医科大学南方医院 钟梓同 赵海金）
(Noble JH, Bean O, et, al. INFORM ASTHMA collaborators. Budesonide-formoterol versus terbutaline reliever in adults with asthma using maintenance inhaled corticosteroids in New Zealand (INFORM ASTHMA): an open-label, parallel-group, randomised, controlled, phase 4 trial. Lancet Respir Med. 2026 Feb;14(2):151-162. doi: 10.1016/S2213-2600(25)00327-3. Epub 2026 Jan 8. PMID: 41520676.)
Abstract(Noble JH, Bean O, et, al. INFORM ASTHMA collaborators. Budesonide-formoterol versus terbutaline reliever in adults with asthma using maintenance inhaled corticosteroids in New Zealand (INFORM ASTHMA): an open-label, parallel-group, randomised, controlled, phase 4 trial. Lancet Respir Med. 2026 Feb;14(2):151-162. doi: 10.1016/S2213-2600(25)00327-3. Epub 2026 Jan 8. PMID: 41520676.)
Background: Recommendations for the use of inhaled corticosteroid-formoterol reliever-based regimens are limited by the absence of randomised controlled trials (RCTs) in patients with asthma using maintenance inhaled corticosteroids, and scarce evidence for the effect on type 2 airway inflammation. We aimed to examine the clinical efficacy and safety of maintenance inhaled corticosteroids plus budesonide-formoterol reliever or terbutaline reliever in patients with mild-to-moderate asthma.
Methods: This open-label, parallel-group, randomised, controlled, phase 4 trial was conducted at Wellington Hospital and two community-based primary care facilities in New Zealand. Eligible participants were aged 16-75 years, had a self-reported doctor's diagnosis of asthma, were using reliever only therapy or maintenance inhaled corticosteroids with short-acting β2-agonist reliever therapy, and were registered with a general practitioner. Participants had to have reported mean reliever use on two or more occasions per week in the 12 weeks before enrolment and had evidence of airway inflammation (FeNO ≥25 parts per billion [ppb]) at screening. Participants were randomly assigned (1:1) to budesonide-formoterol (budesonide 200 μg and formoterol 6 μg) reliever or terbutaline 250 μg reliever therapy using a computer-generated sequence in block sizes of four and six, stratified by region, baseline inhaled corticosteroids maintenance dose, and history of severe asthma exacerbation in the previous 12 months. All participants received maintenance budesonide 200 μg. During a 26-week treatment period, participants attended visits at weeks 0 (screening and randomisation), 13, and 26. The primary outcome was FeNO at week 26, measured in the intention-to-treat (ITT) population. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12622001304729 (completed).
Findings: Between March 28, 2023, and Aug 27, 2024, 290 participants were assessed for eligibility, 109 were ineligible, and 181 were randomly assigned to budesonide-formoterol (n=93) or terbutaline reliever therapy (n=88; ITT population). Participants had a mean age of 33·91 years (SD 15·54). 119 (66%) of 181 participants were female and 62 (34%) were male. Geometric mean FeNO was 62·18 ppb (SD 1·86) at baseline and 39·65 ppb (2·12) at week 26, for the budesonide-formoterol group and 68·03 ppb (1·97) at baseline and 52·98 ppb (2·27) at week 26 for the terbutaline group. Budesonide-formoterol reliever therapy resulted in a mean reduction in geometric mean FeNO of 18·50% (95% CI 2·72-31·73; p=0·024) at week 26 compared with terbutaline reliever therapy. 77 (83%) of 93 participants in the budesonide-formoterol group versus 69 (78%) of 88 in the terbutaline group had at least one adverse event (relative risk 1·06 [95% CI 0·91-1·22]; p=0·46). There were no deaths in the study.
Interpretation: Budesonide-formoterol reliever therapy resulted in a reduction in FeNO compared with terbutaline reliever in adults with asthma using maintenance inhaled corticosteroids. Budesonide-formoterol reliever is a safe and effective alternative to short-acting β2-agonist reliever therapy for adults using maintenance inhaled corticosteroids.
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