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Weekly dupilumab 300 mg versus placebo demonstrated statistically significant, clinically meaningful improvements in histologic and endoscopic outcomes and symptoms in adults and adolescents with eosinophilic esophagitis.
Treatment with weekly dupilumab (Dupixent) reduced peak esophageal intraepithelial eosinophil (EOS) counts and reduced dysphagia symptoms compared with placebo in adult and adolescent patients with eosinophilic esophagitis (EoE), according to findings from a pooled analysis from parts A and B of the pivotal phase 3 LIBERTY-EoE-TREET study that were presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.
In the study, the monoclonal antibody dupilumab reduced esophageal EOS counts by 80.10% from baseline to week 24 compared with a 1.54% increase in the placebo arm. A decline of 6 or more in EOS per high powered field (HPF) was experienced by 59% of those in the dupilumab arm compared with 5.9% in the placebo group (P <.0001).
Patient reported outcomes were collected using the dysphagia symptom questionnaire (DSQ), in which a higher score indicates more severe dysphagia. The absolute change in DSQ from baseline to week 24 was -12.69 with placebo and -23.21 with dupilumab, representing -38.20% and -65.50% change from baseline, respectively.
"The pooled data from part A and part B of the 3-part, phase 3 LIBERTY-EoE-TREET study indicate that weekly dupilumab 300 mg versus placebo demonstrated statistically significant, clinically meaningful improvements in histologic and endoscopic outcomes and symptoms in adults and adolescents with EoE," lead author Evan Dellon, MD, MPH, FACG, Professor of Medicine and Adjunct Professor of Epidemiology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, said during a presentation of the results.
Based on findings from the LIBERTY-EoE-TREET study, the FDA approved dupilumab for adults and adolescents with EoE, provided they were aged 12 or more and weighed 40 kg or more. This approval, which followed a breakthrough therapy designation and a priority review, was granted in May 2022, and represented the first dedicated approval specifically for EoE.
In part A of the study, dupilumab, which blocks IL-4 and IL-13, was given at 300 mg subcutaneously every week from baseline through week 24. In part B, patients received dupilumab either weekly or every 2 weeks at 300 mg. Only those treated with the weekly dose were considered for the analysis (N = 122). Part C, which was not included in this analysis, continued treatment at different doses through week 52 and included a crossover from placebo to dupilumab.
Baseline demographics were similar between arms. In the dupilumab arm, mean DSQ score at baseline was 36.3. Peak EOS count in 3 regions was a mean of 86.9 EOS/HPF. The EoE Endoscopic Reference Score (EREFS) score was 6.7, the histologic scoring system (HSS) grade score was 1.3, and the HSS stage score was also 1.3. Most patients had a comorbid atopic or allergic condition and a third were on a food elimination diet at screening. “In general, this was a pretty inflamed, and difficult-to-treat population that was in this study,” said Dellon.
EREFS changed by -0.41 with placebo and by -3.95 for those treated with dupilumab, which indicated substantially more esophageal remodeling with treatment (P <.0001). At week 24, there was also a -0.82 absolute change from baseline in grade score by HSS with dupilumab compared with a -0.10 change with placebo. HSS stage score was similar, with a -0.09 change in the placebo group and a -0.79 change with dupilumab (P <.0001).
Treatment-emergent adverse events (TEAEs) were experienced by 74.4% of patients in the placebo arm and in 84.4% of those in the dupilumab group. TEAEs leading to discontinuation were experienced by 1.7% of those in the placebo arm and in 2.5% in the dupilumab group. The most common TEAEs in the placebo and dupilumab arms, respectively, were injection site reaction (17.9% vs 19.7%), injection site erythema (12.8% vs 9.8%), injection site swelling (2.6% vs 12.3%), and headache (11.1% vs 6.6%).
“There were no new safety signals noted when pooling the data,” said Dellon.
The oral abstract, “Dupilumab Improves Clinical, Symptomatic, Histologic, and Endoscopic Aspects of EoE up to 24 Weeks: Pooled Results From Parts A and B of Phase 3 LIBERTY-EoE-TREET,” was presented at ACG 2022.