Dupilumab (Dupixent) significantly reduced patient-reported dysphagia among adults with eosinophilic esophagitis enrolled in a randomized trial, investigators reported.
Treatment with this monoclonal antibody also improved histologic disease features and abnormal endoscopic features, compared with placebo, according to investigators in the phase 2 trial, which included 47 patients enrolled at 14 U.S. study sites.
Injection-site erythema and nasopharyngitis were more common among dupilumab-treated versus placebo-treated patients, and there were no serious adverse events or deaths observed, according to cofirst authors Ikuo Hirano, MD, of Northwestern University, Chicago, and Evan S. Dellon, MD, MPH, of the University of North Carolina at Chapel Hill.
“Dupilumab is the first targeted biologic agent to improve dysphagia, histologic and endoscopic measures of disease, as well as esophageal function, and have an acceptable safety profile in adult patients with active eosinophilic esophagitis,” said Dr. Hirano and Dr. Dellon and associates in the journal.
The report on the phase 2 trial included 47 adults with active eosinophilic esophagitis randomized to weekly subcutaneous injections of dupilumab at a dose of 300 mg or placebo. All participants had a score of 5 or higher on the Straumann Dysphagia Instrument (SDI), a patient-reported outcome measure.
Change in SDI score from baseline to week 10, the study primary endpoint, was significantly improved for dupilumab, according to investigators, who reported a least-squares mean change of –3.0 from baseline, versus –1.3 for placebo (P = .0304).
The original plan was to measure dupilumab’s effect on SDI out to week 12 of treatment, but because of technical problems with an electronic diary system used in the trial, there was significant data loss, and this primary endpoint was instead evaluated at week 10, investigators said in their report.
Improvements in SDI scores were apparent as early as week 1 after dupilumab treatment started, they added, noting that 39% of dupilumab-treated patients had an improvement in SDI score of at least 3, compared with just 13% of placebo-treated patients (P = .490).
Dupilumab also improved outcomes measured by the eosinophilic esophagitis histology scoring system (EoE-HSS), including a 68.3% improvement in severity and 54.6% in extent of disease from baseline to week 12, investigators said.
Likewise, dupilumab improved endoscopic outcomes at week 12 as measured by the eosinophilic esophagitis Endoscopic Reference Score (EREFS), and improved esophageal distensibility plateau, a measure of esophageal function, by 18%, compared with placebo, according to the report.
The Food and Drug Administration has approved dupilumab for use in atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis, and has granted orphan drug designation for its use in the treatment of eosinophilic esophagitis, according to Sanofi and Regeneron Pharmaceuticals.
Dupilumab antagonizes the interleukin (IL)–4 receptor-alpha component of the type 2 receptor, thereby inhibiting signaling of IL-4 and IL-13, the investigators noted in their report.
“These results demonstrate that interleukin-4 and interleukin-13 are central pathological mediators of esophageal inflammation and dysfunction in adult patients with active eosinophilic esophagitis,” said investigators in their report.
The anti-IgE monoclonal antibody omalizumab (Xolair) failed to improve dysphagia and histologic features of eosinophilic esophagitis, suggesting the pathogenesis of this disease is not mediated by IgE, they added.
A number of other targeted biologic agents, including the anti–IL-5 agents mepolizumab and reslizumab, have failed to significantly improve dysphagia versus placebo in patients with eosinophilic esophagitis, they added.
The research was sponsored by Sanofi and Regeneron. Several study coauthors indicated that they were current or former employees of those companies. Other study authors provided disclosures related to Adare, Allakos, Banner, Calypso, Enumeral, EsoCap, GlaxoSmithKline, Meritage, Regeneron, Robarts, and Shire, and among others.
SOURCE: Hirano I et al. Gastroenterology. 2019 Oct 5. .
AGA patient education on eosinophilic esophagitis can help your patients better understand the condition. Visit https://www.gastro.org/practice-guidance/gi-patient-center/topic/eosinophilic-esophagitis-eoe.