• Mirna Chehade, Evan S Dellon, Jonathan M Spergel, Margaret H Collins, Marc E Rothenberg, Robert D Pesek, Ikuo Hirano, Ruiqi Liu, Elizabeth Laws, Eric Mortensen, Renata Martincova, Arsalan Shabbir, Eilish McCann, Mohamed A Kamal, Matthew P Kosloski, Jennifer D Hamilton, Carin Samuely, Wei Keat Lim, Matthew F Wipperman, Annamaria Farrell, Naimish Patel, George D Yancopoulos, Lila Glotfelty, and Jennifer Maloney.
• From the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York (M.C.), and Regeneron Pharmaceuticals, Tarrytown (R.L., E. Mortensen, A.S., E. McCann, M.A.K., M.P.K., J.D.H., C.S., W.K.L., M.F.W., A.F., G.D.Y., J.M.) - both in New York; the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill (E.S.D.); the Division of Allergy and Immunology, Children's Hospital of Philadelphia, and the Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania - both in Philadelphia (J.M.S.); the Divisions of Pathology and Laboratory Medicine (M.H.C.) and Allergy and Immunology (M.E.R.), Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati; the Section of Allergy and Immunology, Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock (R.D.P.); the Kenneth Griffin Esophageal Center, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago (I.H.); Sanofi, Bridgewater, NJ (E.L., L.G.); Sanofi, Prague, Czech Republic (R.M.); and Sanofi, Cambridge, MA (N.P.).
• N. Engl. J. Med. 2024 Jun 27; 390 (24): 223922512239-2251.

BackgroundDupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.MethodsIn this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically.ResultsIn Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B.ConclusionsDupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.).Copyright © 2024 Massachusetts Medical Society.

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