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Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis - 03/03/23

Doi : 10.1016/j.jaci.2022.11.021 
Tanawin Nopsopon, MD, MPH a, b, c, Grace Lassiter, MD, MPH d, Ming-Li Chen, MD b, e, G. Caleb Alexander, MD, MS f, g, h, Corinne Keet, MD, PhD i, Hwanhee Hong, PhD j, Ayobami Akenroye, MBChB, MPH, PhD a, f, k,
a Division of Allergy and Clinical Immunology, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 
k Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Mass 
b Harvard T.H. Chan School of Public Health, Boston, Mass 
c Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 
d Department of Anesthesiology, NewYork-Presbyterian/Weill Cornell Medical Center 
e Chung Shan Medical University, Taichung, Taiwan 
f Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md 
g Center for Drug Safety and Effectiveness, Baltimore, Md 
h Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md 
i Division of Pediatric Allergy and Immunology, University of North Carolina, Chapel Hill, NC 
j Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 

Corresponding author: Ayobami Akenroye, MBChB, MPH, PhD, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, 60 Fenwood Rd, Boston, MA 02115.Division of Allergy and Clinical ImmunologyBrigham and Women’s Hospital60 Fenwood RdBostonMA02115

Graphical abstract




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Abstract

Background

It is unclear how the efficacy of tezepelumab, approved for the treatment of type 2 high and low asthma, compares to the efficacy of other biologics for type 2–high asthma.

Objectives

We sought to conduct an indirect comparison of tezepelumab to dupilumab, benralizumab, and mepolizumab in the treatment of eosinophilic asthma.

Methods

The investigators conducted a systematic review and Bayesian network meta-analyses. They identified randomized controlled trials indexed in PubMed, Embase, or Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 2000, and August 12, 2022. Outcomes included exacerbation rates, prebronchodilator FEV1, and the Asthma Control Questionnaire.

Results

Ten randomized controlled trials (n = 9201) met eligibility. Tezepelumab (relative risk: 0.63; 95% credible interval [CI]: 0.46-0.86) was associated with significantly lower exacerbation rates than benralizumab and larger improvements in FEV1 compared to mepolizumab (mean difference [MD]: 66; 95% CI: −33 to 170) and benralizumab (MD: 62; 95% CI: −22 to 150), though the 95% CI crossed the null value of 0. Mepolizumab improved the Asthma Control Questionnaire score the most, but this improvement was not significantly different from that of tezepelumab (tezepelumab vs mepolizumab; MD: 0.14; 95% CI: −0.10 to 0.38). For efficacy by clinically important thresholds, tezepelumab, mepolizumab, and dupilumab achieved a >99% probability of reducing exacerbation rates by ≥50% compared to placebo, but benralizumab had only a 66% probability of doing so. Tezepelumab and dupilumab had a probability of 1.00 of improving prebronchodilator FEV1 by ≥100 mL above placebo. Compared to mepolizumab, dupilumab had >90% chance for improving FEV1 by ≥50 mL, but none of the differences between biologics exceeded 100 mL.

Conclusions

In individuals with eosinophilic asthma, tezepelumab and dupilumab were associated with greater improvements (although below clinical thresholds) in exacerbation rates and lung function than benralizumab or mepolizumab.

Le texte complet de cet article est disponible en PDF.

Key words : Asthma, eosinophilic, tezepelumab, dupilumab, mepolizumab, benralizumab, network meta-analysis, Bayesian, mAb, comparative effectiveness

Abbreviations used : ACQ, CI, FDA, GRADE, MCID, NMA, RCT, RR, SUCRA, T2, TSLP


Plan


 A. Akenroye is supported by the National Institutes of Health/National Institutes on Minority Health and Health Disparities K99/R00 Maximizing Opportunities for Scientific and Academic Independent Careers Award (K99MD015767) and the Brigham and Women’s Hospital Minority Faculty Career Development Award.
 Disclosure of potential conflict of interest: G. C. Alexander is past Chair and a current member of US Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee; is a cofounding principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation, for whom he has served as a paid expert witness; and is a past member of OptumRx’s National Pharmacy and Therapeutics Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies. The rest of the authors declare that they have no relevant conflicts of interest.
 Systematic Review and Network Meta-analysis of the Efficacy of Mepolizumab, Benralizumab, and Dupilumab for the Treatment of Severe Asthma (CRD42021232084).


© 2022  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 151 - N° 3

P. 747-755 - mars 2023 Retour au numéro
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