Dupilumab Reduces Type 2 Biomarker Levels in Post Hoc Analysis

Monoclonal antibody biologic dupilumab (Dupixent) has been found to improve measures of fractional exhaled nitric oxide (FeNO) and blood eosinophils in asthmatic patients with comorbid chronic rhinosinusitis and with or without nasal polyposis (CRSwNP/CRSsNP).

In new post hoc data from the LIBERTY ASTHMA QUEST trial, presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting in San Francisco, CA, this week, investigators showed the Sanofi-Regeneron’s therapy’s capability in treating type 2 inflammation biomarkers in comorbid subgroups of patients with uncontrolled, moderate to severe asthma.

The phase 3 study assessed add-on dupilumab at doses of 200 mg and 300 mg once every 2 weeks versus placebo in asthmatic patients with either CRSwNP or CRSsNP, with a medical history or ongoing symptoms of CRS. CRS/NP was self-reported in 382 patients from the trial.

In the primary results of the LIBERTY ASTHMA QUEST trial, the interleukin-4 and -13 pathway inhibitor was assessed for its benefits in type 2 inflammation and health-related quality of life improvements in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis further assessed its particular effects on type 2 biomarkers—in a slightly different patient population.

Investigators assessed for changes from baseline over time for FeNO, total Immunoglobulin E (IgE), and eotaxin-3—a lung-based protein shown to attract eosinophils in patients with inflammatory conditions.

Baseline FeNO and eotaxin-3 levels were greater in patients with CRSwNP than in those without. By week 12 of treatment, all dupilumab-treated patient groups reported evident biomarker suppression. By week 52, both patients with CRSwNP and CRSsNP reported significant biomarker suppression. The 200 mg and 300 mg patients with CRSwNP reported median percentage changes of -46.2/-37.7 in FeNO; -74.8/76.8 in IgE; and -47.7/-50.9 in eotaxin-3, respectively (P ≤ .0001).

The 200 mg and 300 mg patients with CRSsNP reported median percentage changes of -31.0/-35.9 in FeNO; -67.3/-67.7 in IgE; and -31.8/-37.2 in eotaxin-3, respectively (P < .0001).

Investigators also observed common adverse injection-site reactions in patients treated with dupilumab groups, versus placebo (15%/18% vs 5%/10%).

The findings supporting the therapy’s benefit in treating type 2 biomarkers in this patient group were presented at AAAAI on the same day as additional post hoc LIBERTY ASTHMA QUEST data showed dupilumab significantly reduced severe asthma exacerbations and improved lung function in patients with moderate-to-severe asthma, both with and without comorbid allergic rhinitis.

In an interview with MD Magazine® while at AAAAI, study author Neil Graham, MD, MPH, explained, now that the drug has been indicated for the treatment of 2 different diseases associated with the same inflammatory pathways, the potential of dupilumab in the inflammatory field is fairly extensive.

“We always felt that would be the real proof of the pudding, because you have essentially 3 different conditions in the same patient, all of which we think are type 2—and we now know are type 2 because dupilumab works for all of them,” Graham said.

Graham said Sanofi-Regeneron is currently exploring the therapy for additional respiratory, dermatological, and food-allergic conditions, as well as eosinophilic esophagitis—a condition which currently has no marketed therapies.

“The science has come a long way just in the last 9 years I've been working in the area,” Graham said. “And this drug is positioned, we think very nicely, to meet most of those indications, potentially.”

The study, "Dupilumab Suppresses Type 2 Biomarkers in Asthma Patients With and Without Comorbid Chronic Rhinosinusitis With or Without Nasal Polyposis (CRS/NP): Post Hoc Analysis of LIBERTY ASTHMA QUEST," was published online in The Journal of Allergy and Clinical Immunology.