Introduction
Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease with increasing incidence and prevalence. Patients with EoE usually present with symptoms of dysphagia that impact their quality of life. In the 3-part, Phase 3 LIBERTY EoE TREET study (NCT03633617), dupilumab improved histologic, symptomatic, and endoscopic aspects of EoE up to 52 weeks.
Aims & Methods
The aim of this analysis was to assess the effect of dupilumab on symptoms of dysphagia in the 28-week extended treatment period of LIBERTY EoE TREET in patients who switched from placebo to dupilumab at 24 weeks. In Parts A and B, patients received dupilumab 300 mg or placebo weekly (qw) for 24 weeks. Patients who completed Parts A and B entered Part C - a 28-week extended treatment period in which all patients received dupilumab 300 mg qw; patients entering Part C remained blinded to their treatment in Parts A and B. Dysphagia Symptom Questionnaire (DSQ) score and number of days with dysphagia (assessed using the DSQ) were calculated over a 14-day period. Percent change in DSQ score and in number of days with dysphagia from Week 24 through Week 52 vs the Week 24 baseline were assessed for patients who switched from placebo to dupilumab 300 mg qw at Week 24 and or continued on dupilumab 300 mg.
Results
Mean (SD) DSQ score after 24 weeks of placebo was 24.7 (19.6) and 21.5 (18.4) in Parts A (n=37) and B (n=37), respectively. Significant improvements in DSQ score were observed within 4 weeks of the switch to dupilumab 300 mg qw (mean percent reduction: 31.5% and 29.9%). After 28 weeks (at Week 52), mean percent reduction in DSQ score was 63.6% and 59.7%. After 24 weeks of placebo, mean (SD) days with dysphagia was 6.6 (4.7) and 6.0 (4.7) in Parts A and B, respectively. At Week 52, there was a 63.2% and 46.8% mean reduction in the number of days with dysphagia.
Conclusion
In patients who initially received 24 weeks of placebo, weekly treatment with dupilumab 300 mg resulted in rapid (within 4 weeks) and sustained (up to 28 weeks) improvement in symptoms of dysphagia as assessed by the DSQ score. The magnitude of the improvement in dysphagia observed after switching from placebo to dupilumab was similar to that seen at 4 weeks in patients who originally initiated dupilumab in Parts A and B of the study.
Disclosure
Dellon ES. Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Dr. Falk Pharma, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio – consultant. Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda – research funding. Allakos, Aqilion, Holoclara, Invea – educational grants.
Chehade M. Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, and Shire/Takeda ‒ consultant. Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Celgene/BMS, Danone, Regeneron Pharmaceuticals Inc., and Shire/Takeda ‒ research funding.
Bredenoord AJ. Alimentiv, Aqilion, AstraZeneca, Dr. Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., and Sanofi ‒ consultant. Dr Falk Pharma, Norgine, Nutricia, Sanofi, SST, Regeneron Pharmaceuticals Inc., and Thelial ‒ research funding. Alimentiv, Aqilion, AstraZeneca, Dr Falk Pharma, Eupraxia, Laborie, Medtronic, Reckitt, Regeneron Pharmaceuticals Inc., and Sanofi ‒ speaker fees.
Spergel JM. Allakos, DBV Technologies, Novartis, Regeneron Pharmaceuticals Inc., and Shire/Takeda – consultant. DBV Technologies and Regeneron Pharmaceuticals Inc. ‒ research grant support.
Xia C, McCann E, Khodzhayev A, Radwan A. Regeneron Pharmaceuticals Inc. – employees and shareholders.
Tilton ST, Pela T, Jacob-Nara JA. Sanofi – employee, may hold stock and/or stock options in the company.
