• Marc E Rothenberg, Evan S Dellon, Margaret H Collins, Albert J Bredenoord, Ikuo Hirano, Kathryn A Peterson, Laura Brooks, Julie M Caldwell, Harald Fjällbrant, Hanna Grindebacke, Calvin N Ho, Matthew Keith, Christopher McCrae, Dominic Sinibaldi, Wendy I White, Catherine J Datto, and MESSINA Trial Investigators.
• From the Divisions of Allergy and Immunology (M.E.R., J.M.C.) and Pathology and Laboratory Medicine (M.H.C.), Department of Pediatrics, and the Department of Pathology and Laboratory Medicine (M.H.C.), University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati; the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill (E.S.D.); the Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam (A.J.B.); the Kenneth C. Griffin Esophageal Center, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago (I.H.); the Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City (K.A.P.); Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development, AstraZeneca, Cambridge, United Kingdom (L.B.); Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (H.F., H.G.); and Patient Centered Science, BioPharmaceuticals Medical Evidence (C.N.H.), Late-stage Respiratory and Immunology (M.K., C.J.D.) and Translational Science and Experimental Medicine, Early Respiratory and Immunology (C.M.), BioPharmaceuticals Research and Development, and Data Sciences and AI (D.S.) and Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences (W.I.W.), Research and Development, AstraZeneca, Gaithersburg, MD.
• N. Engl. J. Med. 2024 Jun 27; 390 (24): 225222632252-2263.

BackgroundBenralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.MethodsIn a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24.ResultsA total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events.ConclusionsIn this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).Copyright © 2024 Massachusetts Medical Society.

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