Background

Clinical remission has emerged as an important treatment goal in severe asthma; however, studies have reported variable attainment due to differences in study populations, definitions, and methods. We aimed to perform a systematic review and meta-analysis of clinical remission attainment, definitions, and correlates among patients with severe asthma who have been treated with biologics.

Methods

In this systematic review and meta-analysis, we searched Web of Science, Embase, and MEDLINE, using the keywords “asthma” and “remission”, for studies published between database inception and June 13, 2024, that reported clinical remission among patients with severe asthma treated with biologics. Studies were eligible for inclusion in both the systematic review and meta-analysis if they were published in English language peer-reviewed journals and reported rates of clinical remission for patients treated with biologics for severe asthma. There were no limitations by study design. Two reviewers independently screened identified papers (AS and CR), with disagreements resolved through consensus or referral to a third reviewer (JB). Study-level data on study characteristics, clinical remission definitions, clinical remission attainment, and the potential correlates of clinical remission were extracted independently by two reviewers (AS and CR) using Covidence. We defined a three-component definition of clinical remission, which included use of maintenance oral corticosteroids, exacerbations, and asthma symptom burden, and a four-component definition, which additionally included lung function. We meta-analysed the rate of attainment of clinical remission and assessed the correlates of clinical remission using DerSimonian-Laird random-effects models. Statistical heterogeneity was assessed using the I² statistic. This study was registered with PROSPERO, CRD42024507233.

Findings

Our search identified 3014 potentially eligible studies, of which 1812 were screened. 25 studies were included, which reported 28 analyses of clinical remission attainment. 68 definitions of clinical remission were identified, of which 48 were unique. Little consensus was found between studies in terms of the clinical remission definition, particularly for symptoms and lung function. Eight analyses used the three-component definition of clinical remission and 25 used the four-component definition. The pooled proportion of patients who attained clinical remission was 38% (95% CI 29–47; I²=93%) for the three-component definition and 30% (27–34; I²=83%) for the four-component definition. Several pulmonary factors were associated with lower clinical remission rates, including worse FEV₁ (odds ratio 0·09 [95% CI 0·01–0·92]; I²=87%), worse asthma symptoms (0·23 [0·17–0·33]; I²=0%), longer asthma duration (0·49 [0·32–0·76]; I²=22%), and use of maintenance oral corticosteroids (0·57 [0·40–0·79]; I²=49%). The presence of comorbidities, in particular depression (0·38 [0·23–0·61]; I²=6%) and obesity (0·41 [0·31–0·54]; I²=0%), were important non-pulmonary barriers to clinical remission.

Interpretation

Clinical remission is an achievable goal for a minority of patients with severe asthma treated with biologics. Definitions of clinical remission varied substantially between studies, and materially affected attainment, suggesting an urgent need for further consensus-driven definitions. Longer disease duration, higher asthma severity, and the presence of comorbidities were identified as important barriers to clinical remission, suggesting that earlier intervention with effective treatments and a broader treatable traits approach might improve outcomes.

Funding

Health Data Research UK, Inflammation and Immunity driver project.

中文翻译：

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接受生物制剂治疗的重度哮喘患者的临床缓解达到、定义和相关性：系统评价和荟萃分析

 背景

临床缓解已成为严重哮喘的重要治疗目标;然而，由于研究人群、定义和方法的差异，研究报告了不同的成就。我们旨在对接受生物制剂治疗的严重哮喘患者的临床缓解达到情况、定义和相关性进行系统评价和荟萃分析。

 方法

在本系统综述和荟萃分析中，我们使用关键词 “asthma” 和 “remission” 检索了 Web of Science、Embase 和 MEDLINE，以获取从数据库建立到 2024 年 6 月 13 日发表的、报告了接受生物制剂治疗的严重哮喘患者临床缓解的研究。如果研究发表在英文同行评审期刊上，并且报告了接受生物制剂治疗的严重哮喘患者的临床缓解率，则这些研究有资格纳入系统评价和荟萃分析。研究设计没有限制。两名评价员独立筛选确定的论文 （AS 和 CR），通过协商一致或转介给第三位评价员 （JB） 解决分歧。两名评价员 （AS 和 CR） 使用 Covidence 独立提取了有关研究特征、临床缓解定义、临床缓解实现和临床缓解潜在相关性的研究水平数据。我们定义了临床缓解的三部分定义，其中包括使用维持口服皮质类固醇、恶化和哮喘症状负担，以及一个四部分定义，其中还包括肺功能。我们荟萃分析了临床缓解的实现率，并使用 DerSimonian-Laird 随机效应模型评估了临床缓解的相关性。使用 I² 统计量评估统计异质性。这项研究已在 CRD42024507233 年 PROSPERO 注册。

 发现

我们检索了 3014 项可能符合条件的研究，其中 1812 项被筛选。纳入 25 项研究，报告了 28 项临床缓解实现情况分析。确定了 68 个临床缓解定义，其中 48 个是唯一的。在临床缓解定义方面，特别是症状和肺功能方面，研究之间几乎没有达成共识。8 项分析使用临床缓解的三分量定义，25 项分析使用四分量定义。达到临床缓解的患者的合并比例为 38% （95% CI 29-47;I²=93%）用于三分量定义，30% （27-34;I²=83%）。几种肺部因素与较低的临床缓解率相关，包括较差的 FEV₁ （比值比 0·09 [95% CI 0·01–0·92];I²=87%），哮喘症状更严重 （0·23 [0·17–0·33];I²=0%），哮喘病程较长 （0·49 [0·32–0·76];I²=22%），以及使用维持口服皮质类固醇 （0·57 [0·40–0·79];I²=49%）。存在合并症，尤其是抑郁症 （0·38 [0·23–0·61];I²=6%）和肥胖 （0·41 [0·31–0·54];I²=0%），是临床缓解的重要非肺障碍。

 解释

对于少数接受生物制剂治疗的严重哮喘患者来说，临床缓解是一个可以实现的目标。临床缓解的定义因研究而异，并且对达标有重大影响，这表明迫切需要进一步的共识驱动的定义。更长的病程、更高的哮喘严重程度和合并症的存在被确定为临床缓解的重要障碍，这表明使用有效治疗和更广泛的可治疗特征方法进行早期干预可能会改善结果。

 资金

英国健康数据研究，炎症和免疫驱动项目。