Introduction
Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease characterized by eosinophil-predominant inflammation of the esophagus and symptoms of esophageal dysfunction. Dupilumab is an approved treatment for EoE that demonstrated favorable efficacy and safety in randomized clinical trials. However, there are limited data assessing the use of dupilumab in patients with EoE in the real-world setting. This observational patient registry (EDESIA, NCT06693531) aims to provide long-term, prospective data on the use of dupilumab for the treatment of EoE in a large real-world cohort.
Aims & Methods
EDESIA consists of a screening period of up to 12 weeks, followed by a 3-year assessment period after dupilumab initiation, and targets to enroll 350 patients with EoE from 55 participating sites in the United States (US), including community and academic practice settings. Dupilumab was prescribed for EoE as per US prescribing information. This report analyzed characteristics, treatment patterns, and EoE outcomes among the first 100 patients with EoE aged ≥12 years recruited into the study. Real-world safety of dupilumab was also assessed.
Results
Of the 100 patients enrolled with expected 6-month follow-up to date, mean (standard deviation [SD]) age at study entry was 34.3 (13.5) years, 53% were male, and 96% were White. Mean (SD) duration of diagnosed EoE and age at EoE onset were 5.0 (4.8) and 29.9 (12.7) years, respectively. Over one-third of patients (34%) had food impaction during the 1-year screening period. Comorbid atopic conditions were common at baseline and included allergic rhinitis (64%), food allergy (43%), and asthma (33%). At a pretreatment endoscopy up to 1 year prior to dupilumab initiation (n = 75), 14.7%, 10.7%, and 8.0% met peak eosinophil count (PEC) thresholds of <15 eosinophils/high-power field (eos/hpf), ≤6 eos/hpf, and ≤1 eos/hpf, respectively. After dupilumab initiation, 27 patients underwent ≥1 follow-up endoscopy in the first 6 months; mean (SD) time to first follow-up endoscopy since first dose was 17.5 (7.1) weeks. At first follow-up endoscopy, 92.6%, 92.6%, and 59.3% of patients had PEC <15 eos/hpf, ≤6 eos/hpf, and ≤1 eos/hpf, respectively. For patients who had EoE Endoscopic Reference Score (EREFS) assessment at both endoscopies (n = 20), mean (SD) EREFS total score was 2.85 (2.37) at pretreatment, which reduced to 1.35 (1.27) at first follow-up endoscopy. Mean (SD) EoE Symptom Activity Index total score decreased (improved) from 36.4 (22.6) [n = 98] at pretreatment, to 22.3 (19.6) [n = 93] after 3 months and 17.7 (16.3) [n = 87] after 6 months from starting dupilumab. For the safety population (N = 100), 28% of patients reported ≥1 treatment-emergent adverse event (TEAE); arthralgia (4%), injection-site pruritus, injection-site reaction, abdominal pain, and oropharyngeal pain (all 2%) were the most common TEAEs. TEAEs were rated as mild, moderate, and severe in 22%, 3%, and 3% of cases, respectively. Three patients discontinued from dupilumab and one patient had a treatment interruption due to TEAEs. No deaths or serious TEAEs were reported.
Conclusion
This interim analysis of the first 100 patients with 6 months of follow-up enrolled in the EDESIA registry had findings that were consistent with those observed in randomized clinical studies, indicating dupilumab enabled improvements in histologic, endoscopic, and symptomatic measures in patients with EoE while being well tolerated. Future analyses with a larger sample size and longer follow-up are needed to confirm these findings.
Disclosure
Dellon ES: AbbVie, Adare Pharma Solutions/Ellodi Pharmaceuticals, Alfasigma, ALK, Allakos, Amgen, Anaptysbio, Apogee Therapeutics, Apollo, Aqilion, Arena/Pfizer, AstraZeneca, Bethanamist, Biocryst, Bryn, Calypso, Celgene/Receptos/Bristol Myers Squibb, Celldex, Cyted, Domain, Dr. Falk Pharma, EsoCap, Eupraxia, Ferring, GI Reviewers, GSK, Holoclara, Invea, Knightpoint, LucidDx, Nexstone Immunology/Uniquity Bio, Nutricia, Parexel/Calyx, Phathom Pharmaceuticals, Regeneron Pharmaceuticals Inc., Revolo, Robarts/Alimentiv, Roivant, Sanofi, Shire/Takeda, Target RWE, Third Harmonic Bio, Upstream Bio – consulting fees. Adare Pharma Solutions/Ellodi Pharmaceuticals, Allakos, Arena/Pfizer, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Celldex, Dr. Falk Pharma, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Regeneron Pharmaceuticals Inc., Revolo, Sanofi, Shire/Takeda, Uniquity – research funding. Durrani S, Xia C, Thomas R, Radwan A, deMarchi S: Regeneron Pharmaceuticals Inc. – employees and shareholders. Chehade M: Adare Pharma Solutions/Ellodi Pharmaceuticals, Allakos, Apogee Therapeutics, AstraZeneca, Bristol Myers Squibb, Nexstone Immunology/Uniquity Bio, Phathom Pharmaceuticals, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda – consulting fees. Adare Pharma Solutions/Ellodi Pharmaceuticals, Allakos, AstraZeneca, Celgene, Danone, Regeneron Pharmaceuticals Inc., Shire/Takeda – research funding. Jensen E: Regeneron Pharmaceuticals Inc., Takeda Pharmaceuticals – consulting fees; Regeneron Pharmaceuticals Inc. – research funding; Sanofi – educational grant. Bredenoord AJ: Alimentiv, Aqilion, AstraZeneca, Dr. Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., Sanofi – consulting fees. Alimentiv, Aqilion, AstraZeneca, Dr. Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., Sanofi ‒ speaker fees. Leung J: AbbVie, AstraZeneca, Boston Consulting Group, Branch Professional Education, Cowen, Devine, Eli Lilly, FirstThought, Genzyme Corporation, Guidepoint, Huron Consulting Services LLC, Millimet, Noble Insights, Regeneron Pharmaceuticals Inc., Ribon Therapeutics, Sanofi, Shire Pharmaceuticals, Slingshot, Sophos, Takeda, Tegus, Third Bridge – consulting fees. AbbVie, Regeneron Pharmaceuticals Inc., Sanofi ‒ speaker fees. McGowan E: AstraZeneca, Bristol Myers Squib, Sanofi, Takeda – consulting fees. Regeneron Pharmaceuticals Inc. – research funding. Peterson K: AGA, Alladapt, Amgen, Anaptys Bio, AstraZeneca, Bristol Myers Squibb, Celldex, Ellodi, Invea, Lucid, Nexstone, Regeneron Pharmaceuticals Inc., Sanofi, Takeda – consulting fees. NexEos Bio – stock and options. Regeneron Pharmaceuticals Inc., Takeda – speaker fees. Allakos, Chobani – (unrestricted) grant support. Spergel JM: Allakos, ARS Pharma, DBV Technologies, Merck, Novartis, Readysetfood, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda – consulting fees. Wechsler J: Bristol Myers Squibb, Ellodi, Regeneron/Sanofi – advisory board fees. AstraZeneca, Bristol Myers Squibb, Celldex, Regeneron/Sanofi – consulting fees. Campaign Urging Research for Eosinophilic Disorders (CURED) Foundation Research Scholar, Eosinophilic Gastrointestinal Disorders Program (Medical Director) – employee. InVea Therapeutics, Regeneron/Sanofi, Researched Nutritionals – grant support. Regeneron/Sanofi – speaker fees. Tilton S, Almansa C, Eren D: Sanofi – employees, may hold stock and/or stock options in the company. Schoepfer A: Adare Pharma Solutions, Aptalis, Dr. Falk Pharma – consulting fees. Aptalis, AstraZeneca, Dr. Falk Pharma, GSK, Nestlé, Novartis, Receptos/Bristol Myers Squibb, Regeneron Pharmaceuticals Inc. – research funding.
