Dupilumab Helps Treat Uncontrolled Asthma

Ian D. Pavord, MD

Dupilumab could yield higher rates of clinical remission for patients with moderate-to-severe uncontrolled asthma.

A team, led by Ian Pavord, MD, NIHR Oxford Biomedical Research Centre, University of Oxford, presented new data from an post hoc analysis of LIBERTY ASTHMA QUEST during the American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Annual Meeting.

The Study

In the study, the researchers assessed how dupilumab effects patients with uncontrolled, moderate-to-severe asthma using a multi-component endpoint that represented various dimensions of clinical asthma remission.

Asthma treatment response is categorized by improvement in more than 1 key asthma outcome, such as exacerbations, symptom control, or lung function.

Using clinical asthma remission components—no exacerbations/ 5-item Asthma Control Questionnaire [ACQ-5] total score <1.5/postbronchodilator FEV₁ >80%—the researchers assessed the status of each patient at week 24 and week 52.

The Results

Overall, there were 348 patients treated with either 200 mg or 300 mg of dupilumab every 2 weeks, as well as a control group that included 195 matched placebo treatments.

Each patient included in the study had baseline post-bronchodilator FEV₁ of at least 25 ppb, and eosinophils of at least 150 microL.

The investigators found a higher proportion of patients treated with dupilumab were exacerbation free compared to placebo (Week 24, 83.3% vs. 61.0%; Week 52, 72.7% vs. 46.2%).

In addition, more dupilumab-treated patients were exacerbation-free with an ACQ-5 score less than 1.5 compared to the placebo group (Week 24, 57.5% vs. 27.2%; Week 52, 43.1% vs. 21.5%).

The investigators also found 29.6% (n = 103) dupilumab-treated patients were exacerbation free at week 24 compared to 7.7% (n = 15) of the placebo group, with an ACQ-5 score of less than 1.5 and post-bronchodilator FEV1 of at least 80%, classified as clinical remission. At week 52, 20.1% (n = 70) in the dupilumab group achieved clinical remission, compared to 4.6% (n = 9) in the placebo group.

For the patients who did not achieve clinical remission, the dupilumab group still had fewer exacerbations compared to the placebo group (adjusted annualized rate of severe exacerbations at Week 24/Week 52, 0.63/0.56 vs 1.51/1.46) and improved lung function and asthma control (LS mean change at Week 24/Week 52: 0.20/0.22L vs 0.02/0.03L [FEV₁] and -1.33/-1.51 vs -1.00/-1.11 [ACQ-5 score]).

“Dupilumab treatment could enable patients with uncontrolled moderate-to-severe asthma to achieve a stringent and novel multicomponent endpoint representing clinical asthma remission,” the authors wrote. “Dupilumab substantially reduced exacerbations and improved lung function and asthma control in patients who did not achieve clinical remission.”

Dupilumab

Dupilumab is a fully human VelocImmune-derived monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, both known as central drivers of type 2 inflammation in multiple diseases.

In 2018, the US Food and Drug Administration (FDA) approved dupilumab as an add-on maintenance therapy for adults and adolescents aged 12 years or older, with uncontrolled moderate-to-severe asthma with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.

The study, “Dupilumab Treatment Leads to Clinical Asthma Remission in Patients With Uncontrolled Moderate-to-Severe Asthma With Type 2 Inflammation,” was published online by AAAAI 2021.