Treatment with dupilumab, a monoclonal antibody, significantly improves clinical outcomes and mediates the reversal of persistent airflow obstruction status in patients with uncontrolled asthma.
Asthma is associated with airflow obstruction, which is reversible either spontaneously or with the administration of bronchodilators or corticosteroids. Asthma patients with persistent airflow obstruction (PAO) tend to experience worse asthma outcomes compared to patients without PAO. Dupilumab is a monoclonal antibody known for reducing severe asthma exacerbations and improving pre-bronchodilator forced expiratory volume in one second (FEV1).
A randomized controlled trial investigated the efficacy of dupilumab in improving clinical outcomes among QUEST patients with PAO. The study findings, published in the journal Annals of Allergy, Asthma, and Immunology, indicate that dupilumab treatment in patients suffering from moderate-to-severe asthma improves clinical outcomes and mediates the reversal of PAO status in patients diagnosed with uncontrolled moderate-to-severe asthma.
Baseline Prevalence of Persistent Airflow Obstruction
Among a cohort of 1902 patients diagnosed with moderate-to-severe asthma who participated in the QUEST study, 54% of the patients who received dupilumab treatment and 55% of the patients who received placebo treatment exhibited PAO at baseline.
Improvement in Lung Function
There was a significant improvement in the pre-bronchodilator FEV1 in asthma patients with and without baseline PAO in the dupilumab group compared to the placebo group. The study results also indicated a similar improvement in post-bronchodilator FEV1 in asthma patients with and without baseline PAO. Based on the subgroup analyses, pre-bronchodilator FEV1 demonstrated greater improvement in patients aged < 18 years and 18–64 years in the dupilumab group. Greater improvement was observed in the post-bronchodilator FEV1 in dupilumab-treated patients who had a greater number of exacerbations in the previous year.
Improvement in Airflow Obstruction Status
A greater reversal of the status of PAO was observed in dupilumab-treated patients compared to placebo-treated patients. The inter-group differences in the changes in airflow obstruction status were statistically significant, representing the improved probability of modified PAO status in patients with baseline PAO.
Improvement in the Rate of Severe Exacerbations
Compared to the placebo, dupilumab significantly reduced the annualized rate of severe exacerbations (AER) in patients with baseline PAO. Based on the subgroup analyses, significantly greater reductions in the AER were associated with less time since asthma diagnosis, more exacerbations in the previous year, the absence of the phenotype corresponding to allergic asthma, and an older age at the onset of asthma.
Improvement in Asthma-Related Quality of Life
Measured using the Asthma Quality of Life Questionnaire, dupilumab treatment significantly improved patients’ asthma-related quality of life with and without baseline PAO.
Hanania, N. A., Castro, M., Bateman, E., Pavord, I. D., Papi, A., FitzGerald, J. M., Maspero, J. F., Katelaris, C. H., Singh, D., Daizadeh, N., Altincatal, A., Pandit-Abid, N., Soler, X., Siddiqui, S., Laws, E., Jacob-Nara, J. A., Rowe, P. J., Lederer, D. J., Hardin, M., & Deniz, Y. (2023). Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction. Annals of Allergy, Asthma, and Immunology, 130(2), 206-214.e202. https://doi.org/10.1016/j.anai.2022.10.018