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Real-world efficacy of treatment with Benralizumab, Dupilumab, Mepolizumab and Reslizumab for severe asthma: A systematic review and meta-analysis

Real-world efficacy of treatment with Benralizumab, Dupilumab, Mepolizumab and Reslizumab for severe asthma: A systematic review and meta-analysis
Real-world efficacy of treatment with Benralizumab, Dupilumab, Mepolizumab and Reslizumab for severe asthma: A systematic review and meta-analysis

Background: severe asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates. 

Objective: this systematic review aims to evaluate the real-world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data. Methods: Clinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV 1) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). 

Results: a total of 21 studies examining biologicals in real-world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualzsed exacerbation rate significantly by −3.79 (95% confidence interval [CI] −4.53, −3.04), −3.17 (95% CI −3.74, −2.59) and −6.72 (95% CI −8.47, −4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV 1 (0.17 L 95% CI 0.11, 0.24) and FeNO (−14.23 ppb 95% CI −19.71, −8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV 1 (0.21 L 95% CI 0.08, 0.34). 

Conclusions: these data demonstrate that anti-IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.

FEV, FeNO, asthma, asthma control, benralizumab, dupilumab, exacerbations, mepolizumab, real-world studies, reslizumab
0954-7894
616-627
Charles, David
4c08fc1f-6b79-4bc7-9542-634798faeff8
Shanley, Jemma
a150043f-6a3d-4cd8-b58b-841b12a1bfbf
Temple, Sasha-Nicole
f04639e6-830d-44c8-8fb1-38457927af8e
Rattu, Anna
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Khaleva, Ekaterina
0143fad8-e8b7-4286-997b-368a23488ca8
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Charles, David
4c08fc1f-6b79-4bc7-9542-634798faeff8
Shanley, Jemma
a150043f-6a3d-4cd8-b58b-841b12a1bfbf
Temple, Sasha-Nicole
f04639e6-830d-44c8-8fb1-38457927af8e
Rattu, Anna
72725066-1768-4393-9cee-b416b2ced19d
Khaleva, Ekaterina
0143fad8-e8b7-4286-997b-368a23488ca8
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3

Charles, David, Shanley, Jemma, Temple, Sasha-Nicole, Rattu, Anna, Khaleva, Ekaterina and Roberts, Graham (2022) Real-world efficacy of treatment with Benralizumab, Dupilumab, Mepolizumab and Reslizumab for severe asthma: A systematic review and meta-analysis. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 52 (5), 616-627. (doi:10.1111/cea.14112).

Record type: Review

Abstract

Background: severe asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates. 

Objective: this systematic review aims to evaluate the real-world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data. Methods: Clinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV 1) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). 

Results: a total of 21 studies examining biologicals in real-world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualzsed exacerbation rate significantly by −3.79 (95% confidence interval [CI] −4.53, −3.04), −3.17 (95% CI −3.74, −2.59) and −6.72 (95% CI −8.47, −4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV 1 (0.17 L 95% CI 0.11, 0.24) and FeNO (−14.23 ppb 95% CI −19.71, −8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV 1 (0.21 L 95% CI 0.08, 0.34). 

Conclusions: these data demonstrate that anti-IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.

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Clin Experimental Allergy - 2022 - Charles - Real‐world efficacy of treatment with benralizumab dupilumab mepolizumab and - Version of Record
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e-pub ahead of print date: 16 February 2022
Published date: May 2022
Additional Information: Funding Information: D.C was supported by the University of Southampton's National Institute of Health Research Academic Foundation Programme. G.R is funded by University of Southampton and National Institute of Health Research via Southampton's Biomedical Research Centre. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434 (3TR). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA
Keywords: FEV, FeNO, asthma, asthma control, benralizumab, dupilumab, exacerbations, mepolizumab, real-world studies, reslizumab

Identifiers

Local EPrints ID: 455426
URI: http://eprints.soton.ac.uk/id/eprint/455426
ISSN: 0954-7894
PURE UUID: 7e29a924-a918-4079-9d6d-7482283fcebc
ORCID for Ekaterina Khaleva: ORCID iD orcid.org/0000-0002-2220-7745
ORCID for Graham Roberts: ORCID iD orcid.org/0000-0003-2252-1248

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Date deposited: 21 Mar 2022 17:51
Last modified: 17 Mar 2024 04:02

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Contributors

Author: David Charles
Author: Jemma Shanley
Author: Sasha-Nicole Temple
Author: Anna Rattu
Author: Ekaterina Khaleva ORCID iD
Author: Graham Roberts ORCID iD

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