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Dupilumab treatment provides greatest benefit among mAbs in moderate to severe asthma

Dupilumab treatment produced the lowest incidence of asthma exacerbations and greatest improvements in FEV1 among three currently used mAbs

Dupilumab treatment for 12 months leads to the lowest number of exacerbations and better improvements in FEV1 compared to two commonly used monoclonal antibodies (mAbs), omalizumab or mepolizumab, in adults with moderate to severe asthma, according to comparative analysis by US researchers.

The prevalence of severe asthma varies between 3.6 and 6.1% of all patients with the disease. Individuals with moderate to severe asthma have the opportunity of being treated with several monoclonal antibodies, which target key inflammatory cytokines involved in disease pathogenesis. All of these currently approved biologic therapies have been shown to improve asthma-related outcomes in individuals with asthma uncontrolled with conventional therapy. However, for patients with more than one phenotype such as allergic and eosinophilic asthma, trying to identify the most suitable agent is less clear. In the absence of direct head-to-head comparative trials, researchers can often utilise observational data to emulate a hypothetical pragmatic randomised trial, which is referred to as the target trial.

In the current analysis, the research team emulated a hypothetical randomised trial, making use electronic health records from a large US-based academic health care system. They included adult participants with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL with the objective of comparing the effectiveness of dupilumab treatment with omalizumab or mepolizumab in patients with moderate to severe asthma. The main outcomes of interest were the incidence of asthma-related exacerbations and the change in baseline FEV1 value over 12 months of follow-up.

Dupilumab treatment and asthma outcomes over 12 months

In all, 68 individuals received dupilumab treatment 68 received omalizumab and 65 received mepolizumab.

Over the 12 month period of follow-up, asthma-related exacerbations occurred in 25.0% of those receiving dupilumab treatment compared to 43.1% for mepolizumab (adjusted hazard ratio, aHR = 0.35, 95% CI 0.18 – 0.71). Compared to omalizumab group, asthma exacerbations occurred in 39.7% of patients, giving a corresponding adjusted hazard ratio of 0.42 (95% CI 0.20 – 0.87).

The change in FEV1 for the different agents were 0.11 L (95% CI -0.003 to 0.222 L) for dupilumab versus mepolizumab and 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab.

In patients with eosinophil counts of at least 300 cells/μL, the HR for dupilumab compared to mepolizumab was 0.26 (95% CI 0.10 – 0.67) and 0.24 (95% CI 0.09 – 0.63) for dupilumab vs omalizumab.

Based on these findings, the authors concluded that among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than either omalizumab or mepolizumab.

Akenroye AT et al. Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation. J Allergy Clin Immunol 2023