Long-term Efficacy of Dupilumab Versus Tezepelumab in Asthma: A Matching-Adjusted Indirect Comparison.

Abstract

Dupilumab is approved for moderate-to-severe asthma with an eosinophilic phenotype in the United States and for severe asthma with type 2 inflammation in ex-US countries. Tezepelumab is globally approved for severe asthma. However, their long-term relative efficacy is unknown. To estimate the long-term relative efficacy of dupilumab versus tezepelumab using an unanchored matching-adjusted indirect comparison. Individual patient data for dupilumab from TRAVERSE (N = 1368) and associated parent randomized controlled trials (RCTs) were reweighted to match aggregate tezepelumab data from DESTINATION (N = 475) and associated parent RCTs for prognostic factors and treatment effect modifiers. Outcomes included annualized exacerbation rate (AER) of all asthma exacerbations, AER of asthma exacerbations leading to hospitalization and/or emergency room (ER) visits (baseline of RCTs until the end of TRAVERSE/DESTINATION), and change from baseline (CFB) in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV₁) (baseline of RCTs to week 100/104). Sensitivity analysis (SA) explored key characteristics from the primary analysis. Dupilumab demonstrated a significantly lower AER of all asthma exacerbations (mean difference [MD]: -0.269, 95% confidence interval [CI]: -0.372; -0.166, P < .0001) and a comparable AER of asthma exacerbations leading to hospitalization and/or ER visits (MD: 0.006, 95% CI: -0.016; 0.027, P = .62) compared with tezepelumab. Dupilumab exhibited numerically greater improvement in pre-BD FEV₁ (MD: -0.064L, 95% CI: -0.132; 0.005, P = .07), with a significantly higher CFB in SA (MD: -0.153L; 95% CI: -0.207; -0.099, P < .0001). In the matched cohort, long-term dupilumab treatment resulted in a lower AER of all asthma exacerbations relative to tezepelumab, with lung function improvements observed in SA.