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

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.

Keywords: Asthma; Bayesian; benralizumab; comparative effectiveness; dupilumab; eosinophilic; mAb; mepolizumab; network meta-analysis; tezepelumab.