Clinical remission attainment, definitions, and correlates among patients with severe asthma treated with biologics: a systematic review and meta-analysis.

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 I 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; I=93%) for the three-component definition and 30% (27-34; I=83%) for the four-component definition. Several pulmonary factors were associated with lower clinical remission rates, including worse FEV (odds ratio 0·09 [95% CI 0·01-0·92]; I=87%), worse asthma symptoms (0·23 [0·17-0·33]; I=0%), longer asthma duration (0·49 [0·32-0·76]; I=22%), and use of maintenance oral corticosteroids (0·57 [0·40-0·79]; I=49%). The presence of comorbidities, in particular depression (0·38 [0·23-0·61]; I=6%) and obesity (0·41 [0·31-0·54]; I=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.