Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis
| Autor: | Kathryn A. Peterson, Gary W. Falk, Neil Stahl, Yehudith Assouline-Dayan, Ikuo Hirano, Margaret H. Collins, George D. Yancopoulos, Neil M.H. Graham, Jennifer D. Hamilton, Allen Radin, Evan S. Dellon, Marc E. Rothenberg, Qiong Zhao, Mirna Chehade, Bolanle Akinlade, Zhen Chen, Brian N. Swanson, Gianluca Pirozzi, Alain M. Schoepfer, Leda Mannent, Ekaterina Safroneeva |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Esophageal Mucosa 610 Medicine & health Antibodies Monoclonal Humanized Placebo Gastroenterology law.invention Placebos Young Adult 03 medical and health sciences 0302 clinical medicine Double-Blind Method Randomized controlled trial law 360 Social problems & social services Internal medicine Clinical endpoint Humans Medicine Patient Reported Outcome Measures Esophagus Eosinophilic esophagitis Hepatology business.industry Interleukin-4 Receptor alpha Subunit Eosinophilic Esophagitis Middle Aged Eosinophil medicine.disease Dupilumab Dysphagia Treatment Outcome 030104 developmental biology medicine.anatomical_structure Female 030211 gastroenterology & hepatology Esophagoscopy medicine.symptom Deglutition Disorders business |
| Zdroj: | Hirano, Ikuo; Dellon, Evan S; Hamilton, Jennifer D; Collins, Margaret H; Peterson, Kathryn; Chehade, Mirna; Schoepfer, Alain M; Safroneeva, Ekaterina; Rothenberg, Marc E; Falk, Gary W; Assouline-Dayan, Yehudith; Zhao, Qiong; Chen, Zhen; Swanson, Brian N; Pirozzi, Gianluca; Mannent, Leda; Graham, Neil M H; Akinlade, Bolanle; Stahl, Neil; Yancopoulos, George D; ... (2020). Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology, 158(1), pp. 111-122. Elsevier 10.1053/j.gastro.2019.09.042 |
| Popis: | BACKGROUND & AIMS Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin 4 (IL4) receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE. METHODS We performed a phase 2 study of adults with active EoE (2 dysphagia episodes of dysphagia/week with peak esophageal eosinophil density of 15 or more eosinophils per high-power field), from May 12, 2015 through November 9, 2016 at 14 sites. Subjects were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg; n=23) or placebo (n=24) for 12 weeks. The primary endpoint was change from baseline to week 10 in Straumann dysphagia instrument patient-reported outcome (SDI-PRO) score. We also assessed histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety. RESULTS The mean SDI-PRO score was 6.4 when the study began. In the dupilumab group, SDI-PRO scores were reduced by a mean value of 3.0 at week 10 compared with vs a mean reduction of 1.3 in the placebo group (P=.0304) At week 12, dupilumab reduced peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P |
| Databáze: | OpenAIRE |
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