P0395 - Retrospective Assessment of the Index of Severity for Eosinophilic Esophagitis Using Baseline Disease Characteristics Data from the LIBERTY EoE TREET Study

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

ED

Evan S. Dellon, MD, MPH

University of North Carolina School of Medicine
Chapel Hill, North Carolina

Evan S. Dellon, MD, MPH¹, Seema S. Aceves, MD, PhD², Changming Xia, PhD³, Tiffany Pela, PharmD, MPH⁴, Angela Khodzhayev, PharmD, MS³, Juby A. Jacob-Nara, MD, DHSc, MPH, MBA⁴, Amr Radwan, MBBCh, MA³
¹University of North Carolina School of Medicine, Chapel Hill, NC; ²University of California, San Diego Rady Children’s Hospital, San Diego, CA; ³Regeneron Pharmaceuticals Inc., Tarrytown, NY; ⁴Sanofi, Bridgewater, NJ

Introduction: The Index of Severity for Eosinophilic Esophagitis (EoE) (I-SEE) is a newly developed and as yet unvalidated clinical instrument designed to assess EoE disease severity, using disease features that are meaningful to clinicians and patients. I-SEE comprises three domains that reflect key clinicopathologic features of EoE: symptoms and clinical complications, inflammation, and fibrostenosis. The 3-part, double-blind, placebo-controlled, phase 3 LIBERTY EoE TREET study (NCT03633617) assessed the safety and efficacy of dupilumab in patients with EoE, and successfully supported registration of dupilumab for EoE. The aim of this post-hoc analysis was to retrospectively assess the I-SEE scoring system using baseline disease characteristics data from the LIBERTY EoE TREET study.

Methods: For this analysis, baseline data from patients who were randomized to placebo weekly (qw) and dupilumab 300 mg qw for 24 weeks in Parts A and B of the TREET study, were mapped to the I-SEE parameters and scored as described in the Table. Because several I-SEE components were not available in the existing trial data, we used an algorithm to map relevant data collected in the trial to the I-SEE criteria. Further, multiple elements of the complication subscore could not be summed in the current analysis and “Hospitalization due to EoE” could not be included, as we did not have the cause of prior hospitalizations.

Results: 81 patients enrolled in Part A (42 dupilumab; 39 placebo) and 159 patients in Part B (80 dupilumab; 79 placebo). At baseline (pre-treatment), mean (SD) I-SEE total scores were similar across groups in Part A (placebo: 11.9 [7.50]; dupilumab: 12.5 [6.49]) and Part B (placebo: 11.0 [5.65]; dupilumab: 10.9 [5.74]). These I-SEE scores generally place subjects in the moderate (7–14 points) to severe (≥15 points) range. Mean sub-domain scores were also similar between groups in both Parts A and B (Table).

Discussion: These results show that while it is possible to apply the I-SEE scoring system to EoE clinical trial data retrospectively, some of the I-SEE criteria could not be applied completely due to limitations around mapping the collected TREET data to the I-SEE criteria. This potentially reduced total I-SEE scores. Of note, the I-SEE score was consistent with the enrollment criteria of the TREET study that excluded the most severe esophageal strictures and recent esophageal dilation, features that drive severity in I-SEE.

Domains, mean (SD)	Part A		Part B
Domains, mean (SD)	Placebo (N=39)	Dupilumab qw (N=42)	Placebo (N=79)	Dupilumab qw (N=80)
Symptoms and clinical complications
Symptom Frequency (weekly=1; daily=2; multiple daily=4)	n=39 2.0 (1.01)	n=42 1.9 (1.00)	n=78 1.9 (1.00)	n=80 2.1 (1.00)
Complications (worst per patient: food impaction with ER visit ≥18 years old=2; endoscopy ≥18 years old=2; food impaction with ER visit < 18 years old=4; endoscopy < 18 years old=4; prior esophageal perforation=15; malnutrition with BMI < 5^th percentile=15; decreased growth trajectory=15)	n=39 1.2 (2.52)	n=42 2.1 (3.19)	n=79 1.2 (2.00)	n=80 1.4 (2.53)
Inflammatory features
Endoscopic (localized edema, furrows, or exudates=1; diffuse edema, furrows, or exudates=2)	n=39 1.8 (0.45)	n=42 1.7 (0.59)	n=79 1.9 (0.36)	n=80 1.8 (0.51)
Histologic (15–60 eos/hpf=1; >60 eos/hpf=2)	n=39 1.7 (0.48)	n=42 1.7 (0.48)	n=79 1.8 (0.43)	n=80 1.7 (0.45)
Fibrostenotic features
Endoscopic (EREFS rings 1 or 2, or rings 1 and stricture 1=1; EREFS rings 2 and stricture 1, or stricture 1 and estimated stricture diameter is < 14=2; crepe-paper mucosa=2; narrowing=2; dilation performed as rescue treatment=2; EREFS stricture 3=15; >1 prior dilation=15)	n=39 3.2 (6.10)	n=42 3.0 (5.90)	n=79 2.3 (5.17)	n=80 2.0 (4.72)
Histologic (basal zone hyperplasia or lamina propria fibrosis, or dyskeratotic epithelial cells/surface epithelial alteration if no lamina propria fibrosis=2)	n=39 2.0 (0.00)	n=42 2.0 (0.00)	n=79 1.9 (0.32)	n=80 2.0 (0.00)

Table: Mean (SD) I-SEE sub-domain score at baseline in Parts A and B of the TREET study.

Multiple Complication subscore elements were not summed. “Hospitalization due to EoE” was not included in Complications subscore, as the available data did not identify the cause of prior hospitalizations. BMI, body mass index; eos, eosinophils; ER, emergency room; EREFS, EoE endoscopic reference score; hpf, high-powered field; qw, weekly; SD, standard deviation.

Disclosures:

Evan Dellon: Abbott – Consultant. Abbvie – Consultant. Adare/Ellodi – Consultant, Grant/Research Support. Aimmune – Consultant. Akesobio – Consultant. Alfasigma – Consultant. ALK – Consultant. Allakos – Consultant, Grant/Research Support. Amgen – Consultant. Aqilion – Consultant. Arena/Pfizer – Consultant, Grant/Research Support. Aslan – Consultant. AstraZeneca – Consultant, Grant/Research Support. Avir – Consultant. Banner Pharmaceuticals – Grant/Research Support. Biorasi – Consultant. Calypso – Consultant. Celgene/Receptos/BMS – Consultant, Grant/Research Support. Celldex – Consultant. Eli Lilly – Consultant. EsoCap – Consultant. Eupraxia – Consultant. Ferring – Consultant. Gossamer Bio – Consultant. GSK – Consultant, Grant/Research Support. Holoclara – Consultant, Grant/Research Support. Invea – Consultant, Grant/Research Support. Knightpoint – Consultant. Landos – Consultant. LucidDx – Consultant. Meritage – Grant/Research Support. Miraca – Grant/Research Support. Morphic – Consultant. Nexstone Immunology – Consultant. Nutricia – Consultant, Grant/Research Support. Parexel/Calyx – Consultant. Phathom – Consultant. Regeneron Pharmaceuticals Inc. – Consultant, Grant/Research Support. Revolo Biotherapeutics – Consultant, Grant/Research Support. Robarts/Alimentiv – Consultant. Salix – Consultant. Sanofi – Consultant. Shire/Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Upstream Bio – Consultant.

Seema Aceves: AstraZeneca – Consultant. Bristol Meyer Squibb – Consultant. CURED – Grant/Research Support. Implicit Biosciences – Grant/Research Support. NIH – Grant/Research Support. Regeneron Pharmaceuticals Inc. – Consultant, Speakers Bureau. Sanofi – Consultant, Speakers Bureau. UCSD/Takeda – Intellectual Property/Patents.

Changming Xia: Regeneron Pharmaceuticals Inc. – Employee, Shareholder.

Tiffany Pela: Sanofi – Employee, Stock Options.

Angela Khodzhayev: Regeneron Pharmaceuticals Inc. – Employee, Shareholders.

Juby Jacob-Nara: Sanofi – Employee, Stock Options.

Amr Radwan: Regeneron Pharmaceuticals Inc. – Employee, Shareholder.

Evan S. Dellon, MD, MPH¹, Seema S. Aceves, MD, PhD², Changming Xia, PhD³, Tiffany Pela, PharmD, MPH⁴, Angela Khodzhayev, PharmD, MS³, Juby A. Jacob-Nara, MD, DHSc, MPH, MBA⁴, Amr Radwan, MBBCh, MA³. P0395 - Retrospective Assessment of the Index of Severity for Eosinophilic Esophagitis Using Baseline Disease Characteristics Data from the LIBERTY EoE TREET Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.