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Meta-Analysis
. 2026 Jan;81(1):24-55.
doi: 10.1111/all.70031. Epub 2025 Sep 16.

Predictors of Response to Biologics for Severe Asthma: A Systematic Review and Meta-Analysis

Anna Rattu  1   2 , Piers Dixey  3   4 , David Charles  5 , Chris Brightling  6 , Kian Fan Chung  7 , Apostolos Bossios  8   9   10 , Arnaud Bourdin  11 , Ratko Djukanovic  1   12   13 , Sven-Erik Dahlén  14   15 , Louise Fleming  16 , Rekha Chaudhuri  17 , Erik Melén  18 , Antoine Deschildre  19   20 , Charles Pilette  21 , Gerard H Koppelman  22   23 , Andrew Exley  24 , Freja Anckers  25 , Sarah Miller  26 , Hanna Nielsen  25   27 , Clare Williams  28 , Ekaterina Khaleva  1   29 , Graham Roberts  1   30   31 ; 3TR consortium Respiratory Work Package
Affiliations
Meta-Analysis

Predictors of Response to Biologics for Severe Asthma: A Systematic Review and Meta-Analysis

Anna Rattu et al. Allergy. 2026 Jan.

Abstract

Biologics are effective for severe asthma, but not all patients benefit equally. There is an urgent need to understand which biologic works best for which patient. We systematically searched for predictors of response to biologics (except omalizumab) for severe asthma in four bibliographic databases and two trial registries from 1990 to 2024. Two reviewers screened records, extracted data, and assessed risk of bias using a modified CASP checklist. Data were synthesized narratively, and certainty of evidence assessed using the modified GRADE framework. Comparable studies were meta-analyzed using a random-effects model. From 5853 records, 21 studies were identified investigating predictors of anti-IL5/5Rα, 4Rα, and anti-TSLP response. We found predominantly 'moderate' to 'high' quality evidence that raised blood eosinophil counts (≥ 300 cells/μL), FeNO levels (> 40 ppb), lack of or low OCS dose (< 10 mg/day), and better asthma control predict biologic response. Evidence for the predictive value of other characteristics was limited and mostly 'low' quality. Key reasons for downgrading the evidence were heterogeneous response definitions and imprecision. No data were identified for the pediatric population or biologics targeting the non-T2 pathway. Outside of traditional inflammatory and clinical variables, there is an unmet need for universally applicable predictors of biologic response for severe asthma.

Keywords: biologics; predictive biomarkers; response; severe asthma.

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Conflict of interest statement

Anna Rattu declares funding from the European Commission's Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 831434 (3TR) and National Institute for Health and Care Research (NIHR) Southampton Biomedical Research Centre (BRC). Chris Brightling declares grants and consulting fees from 4D Pharma, Areteia, AstraZeneca (AZ), Chiesi, Genentech, GlaxoSmithKline (GSK), Mologic, Novartis, Regeneron Pharmaceuticals, Roche, and Sanofi paid to his institution; and support from the 3TR EU IMI2 project and NIHR BRC. Kian Fan Chung has received grants from MRC, EPSRC, and GSK paid to his institution; honoraria for speaking engagements for GSK, Novartis, AZ; remuneration for participation in Advisory Board meetings of GSK, AZ, Novartis, Roche, Merck, Trevi, Rickett‐Beckinson, Nocion, Shionogi, and participation in the Scientific Advisory Board of the Clean Breathing Institute supported by Haleon. Apostolos Bossios has received honoraria for lectures from AZ, GSK, Chiesi, and an institutional grant from AZ outside of the submitted work; is head of Assembly five for the European Respiratory Society (ERS), co‐chair of the Nordic Severe Asthma Network (NSAN), member of the steering committee of SHARP, ERS severe asthma Clinical Research Collaboration, and member of the Swedish National Airway Register steering committee. Arnaud Bourdin declares grants from Boehringer Ingelheim, AZ, and GSK; consulting fees from Boehringer Ingelheim, AZ, GSK, Novartis, Chiesi, Sanofi, Celltrion; honoraria from Sanofi, Regeneron, AZ, GSK, Novartis, Boehringer Ingelheim; support for attending meetings from AZ and Sanofi; participates in the advisory board for A.B. science. Ratko Djukanovic declares consulting fees for Synairgen plc, GSK, ZenasBio, Celltrion, ALK Abello; was past co‐chair of the ERS Clinical collaboration on severe asthma (SHARP); shares in Synairgen plc outside of the submitted work. Sven‐Erik Dahlén declares grants from AZ and GSK; consulting fees from Affibody, AZ, Cayman Chemical, GSK, Regeneron, and Sanofi; honoraria for lectures from AZ and Sanofi. Louise J Fleming has received a NIHR HTA grant outside of the submitted work; consulting fees from Sanofi, Regeneron, AZ, GSK; honoraria from AZ and Sanofi. All payments were made to the institution. Rekha Chaudhuri has received a grant from AZ for an investigator‐led study; lecture fees from GSK, AZ, TEVA, Chiesi, Sanofi; support for attending conferences from Chiesi, Sanofi, GSK; participation in Advisory Board Meetings for GSK, AZ, and Celltrion. Erik Melén declares advisory board fees from ALK and AZ outside the submitted work; lecture fees from ALK, AZ, Chiesi, and Sanofi outside the submitted study. Antoine Deschildre has received consulting fees from ALK, Stallergenes‐Greer, GSK, Sanofi, Regeneron, Aimmune Therapeutics, Celltrion, and Viatris; honoraria from Novartis, ALK, GSK, Sanofi, Aimmune Therapeutics, DBV Technologies, Viatris, and Stallergenes‐Greer; support for attending international congresses from Celltrion, ALK, Sanofi, Stallergenes‐Greer, Novartis, AZ, and Aimmune Therapeutics; participation on the Data Safety Monitoring Board for the BOOM study (ClinicalTrials.gov ID: NCT04045301). Charles Pilette has received grants from AZ, Chiesi, GSK, Sanofi; consulting fees from AstraZeneca, Chiesi, GSK; honoraria from ALK‐Abello, AstraZeneca, Chiesi, GSK, and Sanofi. All payments were made to his institution. Gerard H. Koppelman reports receiving research grants from the Netherlands Lung Foundation, Ubbo Emmius Foundation, Zon MW, H2020, and Vertex paid to his institution; consulting fees from AZ paid to his institution; institutional honoraria from AZ, Sanofi, and Boehringer Ingelheim; and is the chair and founder of the ExquAIro foundation. Andrew Exley declares being a minority shareholder in GSK. Ekaterina Khaleva has received grants from the Allergy and Inflammation Research (AAIR) charity and NIHR paid to her institution. Graham Roberts declares 3TR EU IMI2 funding and AZ fees paid to his institution. No other author has any conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
The database and registry search included omalizumab‐related terms, but records pertaining to omalizumab were excluded during screening. CT, clinical trials; EMA, European Medicines Agency; ICTRP, International Clinical Trials Registry Platform.
FIGURE 2
FIGURE 2
Elevated FeNO levels as a predictor of clinical response to Benralizumab. Elevated FeNO levels cut‐offs of 40–44 ppb. AUC, area under curve; CI, confidence intervals.
FIGURE 3
FIGURE 3
Better asthma control at baseline as a predictor of clinical response to mepolizumab. Asthma control measured using the Asthma Control Questionnaire. AUC, area under curve; CI, confidence intervals.
See this image and copyright information in PMC

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