Evan S Dellon, Matthew P Kosloski, Arsalan Shabbir, Lila Glotfelty, Christine Xu, Mohamed A Kamal
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引用次数: 0
Abstract
Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.
Methods: Results for the phase 3 LIBERTY EoE TREET study co-primary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.
Results: A steep initial relationship then plateau was observed between higher dupilumab steady state trough concentrations (Ctrough) and decreased eosinophilic infiltration at Week 24, while a graded exposure-response relationship was observed for symptomatic improvement at Week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation.
Conclusions: The dupilumab 300 mg qw regimen approved for adults and adolescents with EoE weighing ≥40 kg is supported by dose- and exposure-response relationships.
期刊介绍:
Clinical and Translational Gastroenterology (CTG), published on behalf of the American College of Gastroenterology (ACG), is a peer-reviewed open access online journal dedicated to innovative clinical work in the field of gastroenterology and hepatology. CTG hopes to fulfill an unmet need for clinicians and scientists by welcoming novel cohort studies, early-phase clinical trials, qualitative and quantitative epidemiologic research, hypothesis-generating research, studies of novel mechanisms and methodologies including public health interventions, and integration of approaches across organs and disciplines. CTG also welcomes hypothesis-generating small studies, methods papers, and translational research with clear applications to human physiology or disease.
Colon and small bowel
Endoscopy and novel diagnostics
Esophagus
Functional GI disorders
Immunology of the GI tract
Microbiology of the GI tract
Inflammatory bowel disease
Pancreas and biliary tract
Liver
Pathology
Pediatrics
Preventative medicine
Nutrition/obesity
Stomach.