Dupilumab Improves Esophageal Distensibility in Eosinophilic Esophagitis

The monoclonal antibody dupilumab (Dupixent) led to significant improvements in esophageal distensibility among patients with eosinophilic esophagitis, the randomized REMODEL trial showed.

At 24 weeks, patients taking dupilumab had an absolute change in esophageal distensibility plateau diameter from baseline of 1.28 mm versus -0.01 mm in those receiving placebo (least squares mean [LSM] difference 1.30, 95% CI 0.31-2.29, P<0.05), reported Evan S. Dellon, MD, MPH, of the University of North Carolina School of Medicine in Chapel Hill, at the annual Digestive Disease Week meeting.

Patients receiving dupilumab also experienced a 9.8% improvement in esophageal distensibility plateau diameter from baseline compared with a 1.4% improvement in the placebo group (LSM difference 7.78, 95% CI 1.13-14.43), another significant difference.

“The results from REMODEL demonstrate that there is the potential that [dupilumab] could modify the course of the disease as measured by increasing esophageal diameter compared to placebo, in addition to its already established ability to reduce endoscopic and histologic signs of disease and improve symptoms, but the long-term results of REMODEL will help to address that question more completely,” Dellon told MedPage Today. “Future data from this study will allow us to learn the longer-term impact of dupilumab on scarring and narrowing of the esophagus in EoE [eosinophilic esophagitis].”

Dupilumab is an FDA-approved monoclonal antibody that blocks interleukin (IL)-4 and IL-13, which drive the inflammation that causes build-up of eosinophils in the esophagus and esophageal remodeling. In the REMODEL trial, the researchers examined the drug’s effects on countering that remodeling. The EndoFLIP (endolumenal functional lumen imaging probe) tool was used to assess distensibility based on the diameter and pressure of the esophagus.

Mark Malamood, MD, director of benign esophagology at Temple Health Esophageal Disease Program in Philadelphia, told MedPage Today that dupilumab is already indispensable in clinical practice for eosinophilic esophagitis, so it is not surprising that it outperformed placebo here.

“What is new from this study is the confirmation of its effects on the fibrostenotic or ‘remodeling’ aspects of EoE,” said Malamood, who was not involved in the research. “Ongoing eosinophilic inflammation in EoE leads to persistent symptoms but also promotes development of esophageal fibrosis with subsequent luminal narrowing, reduced compliance, and eventual stricturing,” which typically require dilation and medical therapy to manage.

“This study suggests that some of these issues — namely luminal narrowing and reduced compliance — may be treatable with medical therapy alone,” he added.

Despite the small sample size limiting generalizability, the “finding that dupilumab can reverse at least some remodeling effects may shift it from a ‘treatment of last resort’ after failing proton pump inhibitors and/or topical steroids to a more first-line consideration — particularly in patients with evidence of remodeling at the time of diagnosis,” Malamood said.

The trial included 69 adults from 30 sites across the U.S., Brazil, Canada, Israel, and Switzerland. Mean age was 37, and 33% were women.

At baseline, mean EndoFLIP esophageal distensibility plateau diameter was 17.1 mm, mean total Eosinophilic Esophagitis Endoscopic Reference Score (EREFS) was 8.2 (scale 0-18), mean Eosinophilic Esophagitis Histology Scoring System (EoEHSS) grade total score was 1.3 (scale 0-3), and mean EoEHSS stage total score was 1.2 (scale 0-3). Mean peak eosinophil count was 79.6 eosinophils/high-power field (eos/hpf), and mean Dysphagia Symptom Questionnaire score was 29.2 (scale 0-84).

A total of 46 participants received 300 mg of dupilumab and 23 received placebo.

In a subgroup analysis of patients with a baseline esophageal distensibility plateau diameter less than 17 mm, those taking dupilumab had an absolute change from baseline of 1.76 mm compared with -0.49 mm in the placebo group (LSM difference 2.25, 95% CI 0.75-3.75).

Overall, 43% of patients receiving dupilumab experienced a ≥1 mm improvement in esophageal distensibility plateau diameter, compared with only 13% of those receiving placebo, while 28% versus 0% had a ≥2 mm improvement and 15% versus 0% had a ≥3 mm improvement.

The change from baseline in EREFS total score was -4.89 in the dupilumab group and 0.07 in the placebo group (LSM difference -4.96, 95% CI -6.06 to -3.85). Similar significant improvements were seen with dupilumab over placebo in the EREFS inflammatory subscore (-4.21 vs 0.05) and EREFS fibrostenotic subscore (-0.66 vs 0.13). Likewise, the change in EoEHSS grade score was -0.89 with dupilumab and -0.18 with placebo, while the change in EoEHSS stage score was -0.80 and -0.14, respectively. Both differences were significant.

Based on achieving a peak eosinophil count of ≤6 eos/hpf, 59% of dupilumab patients achieved histologic remission compared with 4% of placebo patients (OR 22.24, 95% CI 3.30-149.9). A histologic response (peak eosinophil count <15 eos/hpf) occurred in 78% and 4%, respectively (OR 57.67, 95% CI 7.90-421.04).

Treatment-emergent adverse events (TEAEs) occurred in 62% of dupilumab patients and 48% of placebo patients, most commonly injection site pain/swelling and headache. One dupilumab patient and one placebo patient required rescue treatment, and neither completed the treatment period. No serious TEAEs occurred in either group.