Dupilumab was associated with higher effectiveness than omalizumab and mepolizumab in moderate to severe asthma, according to a study that used observational data to emulate a randomized trial.

“In the absence of head-to-head trials, this generates important evidence to inform clinical decisions,” the study authors wrote. “We conducted a retrospective cohort study that emulated a target trial to compare the effectiveness of omalizumab, dupilumab, and mepolizumab in reducing asthma-related exacerbations and improving lung function in individuals with asthma.”

The results of the study were published in the Journal of Allergy and Clinical Immunology.

The main objective of this study was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab by examining the incidence of asthma-related exacerbations and change in baseline forced expiratory volume per 1 second (FEV1) over a 12-month follow-up.

This study was based on electronic health records from a large US-based academic health system, which included 1024 participants 18 years and older with baseline immunoglobulin E (IgE) levels between 30 to 700 IU/mL and peripheral eosinophil counts of at least 150 cells/mL from March 2016 to August 2021.

In total, the study included 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab, after exclusion.

Throughout the 12-month follow-up, 31 exacerbations occurred over 68 person-years (0.46 exacerbations per person-year) in the dupilumab group, 63 over 68 person-years (0.93 per person-year) in the omalizumab group, and 86 over 65 person-years (1.32 per person-year) in the mepolizumab group.

Using adjusted incidence rate ratios (IRRs), the researchers found the following among the 3 groups:

  • Dupilumab vs mepolizumab (IRR, 0.28; 95% CI, 0.09-0.84)
  • Dupilumab vs omalizumab (IRR, 0.36; 95% CI, 0.12-1.09)
  • Omalizumab vs mepolizumab (IRR, 0.78; 95% CI, 0.32-1.91)

Additionally, the researchers compared baseline FEV1 scores among biologics groups:

  • Dupilumab vs mepolizumab (FEV1, 0.11; 95% CI, –0.033 to 0.222)
  • Dupilumab vs omalizumab (FEV1, 0.082; 95% CI, –0.040 to 0.204)
  • Omalizumab vs mepolizumab (FEV1, 0.026; 95% CI, –0.083 to 0.140)

As a result, the researchers found that dupilumab was associated with greater improvements in asthma-related exacerbations and FEV1 value compared with mepolizumab and omalizumab among patients with asthma and high eosinophil counts.

The researchers believe these results may be due to dupilumab’s mechanism of action, as it blocks the IL-13 signaling that may cause the airway hyperactivity, goblet cell hyperplasia, and smooth muscle dysfunction often seen with asthma.

Although this was an observational study with a small sample size population, the researchers of this study believe they reduced the study’s limitations by emulating a trial using real-world data and adjusting for these factors in their analysis.

They note that more research needs to be done on to fully evaluate the effectiveness of these biologics, as well as examine the overall safety of dupilumab.

“These data add to indirect comparisons of clinical trials to suggest that dupilumab may be a better choice for multiply eligible patients,” the researchers wrote. “Additional research including multiply eligible individuals or individuals who meet criteria for both eosinophilic and allergic asthma is needed to generate evidence about whether there is a hierarchy of phenotypes in these individuals—that is, whether the allergic phenotype should be targeted before the eosinophilic phenotype in these individuals or vice versa.”


Akenroye AT, Segal JB, Zhou G, et al. Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: a target trial emulation. J Allergy Clin Immunol. Published online February 2, 2023. doi:10.1016/j.jaci.2023.01.020

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