Dupilumab promising as treatment for eosinophilic oesophagitis

Dupilumab at a 300 mg dose was tested as a weekly or bi-weekly regimen for patients with eosinophilic oesophagitis in the phase 3 LIBERTY EOE TREET trial. Although only 1 of the 2 co-primary study endpoints was reached, most secondary endpoints were in favour of dupilumab.

Symptoms of oesophageal dysfunction and a mostly eosinophil inflammation in the tissue are typical for eosinophilic oesophagitis (EoE), a chronic and progressive condition [1]. As the inflammation is T2-driven, dupilumab was a candidate for treatment and it was thus evaluated in the 3-part phase 3 LIBERTY EOE TREET trial (NCT03633617) [2].

Prof. Evan S. Dellon (University of North Carolina School of Medicine, NC, USA) presented the 24-week results of study part B, in which 240 adults and adolescents with EoE were treated with placebo or weekly or bi-weekly dupilumab 300 mg. The primary endpoint consisted of 2 measures: the rate reaching an oesophageal intraepithelial eosinophil count (eosC) ≤6/high-power field (hpf) on one hand, and the absolute change in dysphagia assessed by the self-reported Dysphagia Symptom Questionnaire (DSQ) score on the other. The percent change of DSQ was among the secondary endpoints. At baseline the mean eosC/hpf ranged from 84.3 to 89.2 in the 3 study groups, reflecting severe inflammation. The mean DSQ score was 36.7. A prior history of dilative treatment was present in 35.4%, while 73.3% had already been treated with swallowed topical steroids.

Looking at the components of the primary endpoint at week 24, the ratios of achieving an eosC ≤6/hpf were 58.8% with a weekly and 60.5% with a bi-weekly dose in the dupilumab groups compared with 6.3% for placebo (P<0.0001 for both comparisons). Patients receiving weekly dupilumab also had better improvement in patient-reported DSQ scores. However, significance was not reached in the bi-weekly dupilumab group versus placebo for absolute nor percental difference: weekly dupilumab -23.78 and bi-weekly dupilumab -14.37 versus placebo -13.86 (P<0.0001 and P=0.8, respectively).

In terms of secondary outcomes, dupilumab demonstrated significant superiority over placebo. Percentages for reaching a peak eosC <15 were 82.5 (weekly dupilumab)/79.0% (bi-weekly dupilumab) versus 7.6% (placebo). Also, absolute LS means of Endoscopic Reference Score (ERFS), EoE Histologic Scoring System (HSS) grade, and EoE-HSS stage scores were significantly more ameliorated by the study drug (P<0.0001 for all comparisons). In the assessment for gene signatures in type 2 inflammation and EoE diagnostic panel, a positive influence by dupilumab was also observed. There was overall good tolerability of the study drug.

In summary, Prof. Dellon expressed that weekly dupilumab 300 mg improved clinical, symptomatic, histologic, endoscopic, and molecular aspects of EoE and was well tolerated up to 24 weeks.

1. Dellon ES, et al. Gastroenterology. 2018 Oct;155(4):1022–1033.e10.
2. Dellon ES, et al. Clinical and histological improvements with weekly dupilumab treatment in adult and adolescent patients with eosinophilic esophagitis at week 24: weekly and every 2 weeks’ results from part B of 3-part LIBERTY EOE TREET study. Lecture 867a, Digestive Disease Week 2022, 21–24 May, San Diego, CA, USA.

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Posted on 14 June 2022