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Meta-Analysis
. 2024 Apr 24;33(172):230238.
doi: 10.1183/16000617.0238-2023. Print 2024 Apr 30.

Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials

Christos Kyriakopoulos  1 , Athena Gogali  1 , Georgios Markozannes  2 , Konstantinos Kostikas  3
Affiliations
Meta-Analysis

Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials

Christos Kyriakopoulos et al. Eur Respir Rev. .

Abstract

Background: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab.

Methods: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety.

Results: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51-0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27-0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09-0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI -0.46--0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26-0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile.

Conclusions: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.

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Conflict of interest statement

Conflict of interest: A. Gogali has received consulting fees from Boehringer Ingelheim and Chiesi; and payment or honoraria for lectures, presentations or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK and Novartis. K. Kostikas has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis, Pfizer and Sanofi Genzyme; and payment or honoraria for lectures, presentations or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis, Pfizer and Sanofi Genzyme. K. Kostikas is a member of the GOLD Assembly. C. Kyriakopoulos and G. Markozannes declare no competing interests.

Figures

FIGURE 1
FIGURE 1
Systematic review and meta-analysis flow-diagram illustrating systematic search and screening strategy, including number of studies meeting eligibility criteria and number of excluded studies.
FIGURE 2
FIGURE 2
a) Forest plot of asthma exacerbations rate ratios comparing biologic agents and control treatments. b) Forest plot of hospitalisations due to asthma exacerbation rate ratios comparing biologic agents and control treatments. Sample sizes are given for participants receiving biologic agent and participants receiving standard of care treatment, included in the study, when data were available. Summary estimates presented separately for each biologic agent category. DL: DerSimonian and Laird method IL: interleukin; TSLP: thymic stromal lymphopoietin.
FIGURE 3
FIGURE 3
Forest plot of the mean change difference in forced expiratory volume in 1 s comparing biologic agents and control treatments. Sample sizes are given for the total number of participants and the participants receiving intervention included in the study. Summary estimates presented separately for each biologic agent category. DL: DerSimonian and Laird method; IL: interleukin; TSLP: thymic stromal lymphopoietin.
FIGURE 4
FIGURE 4
a) Forest plot of the mean change difference in asthma control questionnaire comparing biologic agents and control treatment. b) Forest plot of the mean change difference in asthma quality of life questionnaire (AQLQ) comparing biologic agents and control treatment. Sample sizes are given for the total number of participants and the participants receiving intervention included in the study. Summary estimates presented separately for each biologic agent category. DL: DerSimonian and Laird method; IL: interleukin; TSLP: thymic stromal lymphopoietin.
FIGURE 5
FIGURE 5
a) Forest plot of oral corticosteroids reduction to doses <5 mg·day−1 prednisolone risk ratios comparing biologic agents and control treatment. Sample sizes are given for participants receiving biologic agent and participants receiving standard of care treatment, included in the study, when data were available. Summary estimates presented separately for each biologic agent category. b) Forest plot of oral corticosteroids dose reduction >50% risk ratios comparing biologic agents and control treatment. Sample sizes are given for the total number of participants and the participants receiving intervention included in the study. Summary estimates presented separately for each biologic agent category. c) Forest plot of oral corticosteroids discontinuation risk ratios comparing biologic agents and control treatment. Sample sizes are given for the total number of participants and the participants receiving intervention included in the study. Summary estimates presented separately for each biologic agent category. d) Forest plot of the mean change difference of oral corticosteroids reduction (%) comparing biologic agents and control treatment. Sample sizes are given for the total number of participants and the participants receiving intervention included in the study. Summary estimates presented separately for each biologic agent category. DL: DerSimonian and Laird method; IL: interleukin; TSLP: thymic stromal lymphopoietin.
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