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.

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.

我们的目标是检查维持性吸入性皮质类固醇加布地奈德-福莫特罗缓解治疗或特布他林缓解治疗在轻度至中度哮喘患者中的临床疗效和安全性。

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.

这是一项开放标签、平行组、随机对照的4期试验，于新西兰惠灵顿医院及两家社区基础初级保健机构进行。

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.

符合条件的参与者年龄在16-75岁之间，自我报告有医生诊断的哮喘病史，仅使用缓解治疗药物或维持吸入性皮质类固醇与短效β2受体激动剂缓解治疗，并已在全科医生处注册登记。

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.

参与者必须报告在入组前的12周内至少有两次每周平均使用缓解药物，并且在筛选时有气道炎症的证据（FeNO ≥25 ppb）。

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.

参与者按1:1的比例随机分配至布地奈德-福莫特罗（布地奈德200微克和福莫特罗6微克）缓解治疗组或特布他林250微克缓解治疗组，使用计算机生成的序列，以四和六的区块大小进行分层，按地区、基线吸入性皮质类固醇维持剂量和过去12个月内的严重哮喘加重史进行分层。

All participants received maintenance budesonide 200 μg.

所有参与者接受了布地奈德200微克的维持治疗。

During a 26-week treatment period, participants attended visits at weeks 0 (screening and randomisation), 13, and 26.

在为期26周的治疗期间，参与者在第0周（筛查和随机化）、第13周和第26周进行了随访。

The primary outcome was FeNO at week 26, measured in the intention-to-treat(ITT) population.

主要结果是第26周的呼出气一氧化氮分数(FeNO)，在意向治疗(ITT)人群中测量。

This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12622001304729 (completed).

该试验已在澳大利亚新西兰临床试验注册处注册，注册号为ACTRN12622001304729（已完成）。

Results

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).

2023年3月28日至2024年8月27日期间，共有290名参与者接受了资格评估，其中109人不符合条件，余下的181人被随机分配至布地奈德-福莫特罗组（n=93）或特布他林缓解治疗组（n=88；意向治疗人群）。

Participants had a mean age of 33·91 years (SD 15·54). 119 (66%) of 181 participants were female and 62 (34%) were male.

参与者的平均年龄为33.91岁（标准差15.54）。在181名参与者中，有119名（66%）为女性，62名（34%）为男性。

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.

基线时，布地奈德-福莫特罗组的几何平均FeNO为62.18 ppb（标准差1.86），第26周时为39.65 ppb（2.12），而特布他林组基线时为68.03 ppb（1.97），第26周时为52.98 ppb（2.27）。

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).

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周时使几何平均FeNO的平均降低率为18.50%（95% 置信区间 2.72-31.73; p=0.024）。布地奈德-福莫特罗组的93名参与者中有77人（83%），而特布他林组的88名中有69人（78%）至少发生了一次不良事件（相对风险1.06 [95% 置信区间 0.91-1.22]; p=0.46）。

There were no deaths in the study.

研究中没有发生死亡事件。

interpretation

Budesonide-formoterol reliever therapy resulted in a reduction in FeNO compared with terbutaline reliever in adults with asthma using maintenance inhaled corticosteroids.

在使用维持吸入性皮质类固醇治疗的成人哮喘患者中，布地奈德-福莫特罗缓解治疗相较于特布他林缓解治疗，导致呼出气一氧化氮（FeNO）水平降低。

Budesonide-formoterol reliever is a safe and effective alternative to short-acting β2-agonist reliever therapy for adults using maintenance inhaled corticosteroids.

布地奈德-福莫特罗缓解剂是对于使用维持吸入性皮质类固醇的成人来说，一种安全且有效的短效β2受体激动剂缓解治疗的替代品。

funding

AstraZeneca.

阿斯利康。