Ikuo Hirano1, Margaret H Collins2, David A Katzka3, Vincent A Mukkada4, Gary W Falk5, Robin Morey6, Nirav K Desai7, Lan Lan6, James Williams7, Evan S Dellon8. 1. Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address: i-hirano@northwestern.edu. 2. Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. 3. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. 4. Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. 5. Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 6. Takeda Development Center Americas, Inc, Lexington, Massachusetts. 7. Takeda Development Center Americas, Inc, Cambridge, Massachusetts. 8. Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Abstract
BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration. METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined. RESULTS: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Δ-3.9 [95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Δ-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity. CONCLUSIONS: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.
BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration. METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined. RESULTS: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Δ-3.9 [95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Δ-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity. CONCLUSIONS: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.
Authors: Evan S Dellon; Paneez Khoury; Amanda B Muir; Chris A Liacouras; Ekaterina Safroneeva; Dan Atkins; Margaret H Collins; Nirmala Gonsalves; Gary W Falk; Jonathan M Spergel; Ikuo Hirano; Mirna Chehade; Alain M Schoepfer; Calies Menard-Katcher; David A Katzka; Peter A Bonis; Albert J Bredenoord; Bob Geng; Elizabeth T Jensen; Robert D Pesek; Paul Feuerstadt; Sandeep K Gupta; Alfredo J Lucendo; Robert M Genta; Girish Hiremath; Emily C McGowan; Fouad J Moawad; Kathryn A Peterson; Marc E Rothenberg; Alex Straumann; Glenn T Furuta; Seema S Aceves Journal: J Allergy Clin Immunol Date: 2022-05-20 Impact factor: 14.290
Authors: Evan S Dellon; Paneez Khoury; Amanda B Muir; Chris A Liacouras; Ekaterina Safroneeva; Dan Atkins; Margaret H Collins; Nirmala Gonsalves; Gary W Falk; Jonathan M Spergel; Ikuo Hirano; Mirna Chehade; Alain M Schoepfer; Calies Menard-Katcher; David A Katzka; Peter A Bonis; Albert J Bredenoord; Bob Geng; Elizabeth T Jensen; Robert D Pesek; Paul Feuerstadt; Sandeep K Gupta; Alfredo J Lucendo; Robert M Genta; Girish Hiremath; Emily C McGowan; Fouad J Moawad; Kathryn A Peterson; Marc E Rothenberg; Alex Straumann; Glenn T Furuta; Seema S Aceves Journal: Gastroenterology Date: 2022-05-20 Impact factor: 33.883
Authors: Sandeep K Gupta; Malcolm Hill; Joanne M Vitanza; Robert H Farber; Nirav K Desai; James Williams; Ivy H Song Journal: J Pediatr Gastroenterol Nutr Date: 2022-06-06 Impact factor: 3.288
Authors: Stephan Miehlke; Christoph Schlag; Alfredo J Lucendo; Luc Biedermann; Cecilio Santander Vaquero; Christoph Schmoecker; Jamal Hayat; Petr Hruz; Constanza Ciriza de Los Rios; Albert Jan Bredenoord; Michael Vieth; Alain Schoepfer; Stephen Attwood; Ralph Mueller; Sarah Burrack; Roland Greinwald; Alex Straumann Journal: United European Gastroenterol J Date: 2022-04 Impact factor: 4.623