Evan S Dellon1, Nirmala Gonsalves2, Marc E Rothenberg3, Ikuo Hirano2, Mirna Chehade4, Kathryn A Peterson5, Gary W Falk6, Joseph A Murray7, Lauren T Gehman8, Alan T Chang8, Bhupinder Singh8, Henrik S Rasmussen8, Robert M Genta9. 1. University of North Carolina, Chapel Hill, North Carolina. Electronic address: edellon@med.unc.edu. 2. Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 3. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. 4. Icahn School of Medicine at Mount Sinai, New York, New York. 5. University of Utah, Salt Lake City, Utah. 6. University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 7. Mayo Clinic Rochester, Rochester, Minnesota. 8. Allakos, Inc, Redwood City, California. 9. Baylor College of Medicine, Houston, Texas.
Abstract
BACKGROUND & AIMS: Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD. METHODS: Subjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings. RESULTS: Of 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis-an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts. CONCLUSIONS: In an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. (ClinicalTrials.gov, Number: NCT03496571).
BACKGROUND & AIMS: Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD. METHODS: Subjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings. RESULTS: Of 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis-an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts. CONCLUSIONS: In an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. (ClinicalTrials.gov, Number: NCT03496571).
Authors: Tetsuo Shoda; Ting Wen; Julie M Caldwell; Margaret H Collins; John A Besse; Garrett A Osswald; J Pablo Abonia; Nicoleta C Arva; Dan Atkins; Kelley E Capocelli; Evan S Dellon; Gary W Falk; Nirmala Gonsalves; Sandeep K Gupta; Ikuo Hirano; Vincent A Mukkada; Philip E Putnam; Rachel M Sheridan; Amanda K Rudman Spergel; Jonathan M Spergel; Joshua B Wechsler; Guang-Yu Yang; Seema S Aceves; Glenn T Furuta; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2019-11-16 Impact factor: 10.793
Authors: M M Walker; N J Talley; M Prabhakar; C J Pennaneac'h; P Aro; J Ronkainen; T Storskrubb; W S Harmsen; A R Zinsmeister; L Agreus Journal: Aliment Pharmacol Ther Date: 2009-01-17 Impact factor: 8.171
Authors: Ameesh Shah; Amir F Kagalwalla; Nirmala Gonsalves; Hector Melin-Aldana; B U K Li; Ikuo Hirano Journal: Am J Gastroenterol Date: 2009-02-10 Impact factor: 10.864
Authors: Craig C Reed; Robert M Genta; Bradford A Youngblood; Joshua B Wechsler; Evan S Dellon Journal: Clin Gastroenterol Hepatol Date: 2020-08-12 Impact factor: 13.576
Authors: Evan S Dellon; Nirmala Gonsalves; J Pablo Abonia; Jeffrey A Alexander; Nicoleta C Arva; Dan Atkins; Stephen E Attwood; Marcus K H Auth; Dominique D Bailey; Luc Biederman; Carine Blanchard; Peter A Bonis; Paroma Bose; Albert J Bredenoord; Joy W Chang; Mirna Chehade; Margaret H Collins; Carlo Di Lorenzo; Jorge Amil Dias; Ranjan Dohil; Christophe Dupont; Gary W Falk; Cristina T Ferreira; Adam T Fox; Robert M Genta; Thomas Greuter; Sandeep K Gupta; Ikuo Hirano; Girish S Hiremath; Jennifer L Horsley-Silva; Shunji Ishihara; Norihisa Ishimura; Elizabeth T Jensen; Carolina Gutiérrez-Junquera; David A Katzka; Paneez Khoury; Yoshikazu Kinoshita; Kara L Kliewer; Sibylle Koletzko; John Leung; Chris A Liacouras; Alfredo J Lucendo; Lisa J Martin; Emily C McGowan; Calies Menard-Katcher; David C Metz; Talya L Miller; Fouad J Moawad; Amanda B Muir; Vincent A Mukkada; Simon Murch; Quan M Nhu; Ichiro Nomura; Samuel Nurko; Yoshikazu Ohtsuka; Salvatore Oliva; Rok Orel; Alexandra Papadopoulou; Dhyanesh A Patel; Robert D Pesek; Kathryn A Peterson; Hamish Philpott; Philip E Putnam; Joel E Richter; Rachel Rosen; Melanie A Ruffner; Ekaterina Safroneeva; Philipp Schreiner; Alain Schoepfer; Shauna R Schroeder; Neil Shah; Rhonda F Souza; Stuart J Spechler; Jonathan M Spergel; Alex Straumann; Nicholas J Talley; Nikhil Thapar; Yvan Vandenplas; Rajitha D Venkatesh; Mario C Vieira; Ulrike von Arnim; Marjorie M Walker; Joshua B Wechsler; Barry K Wershil; Benjamin L Wright; Yoshiyuki Yamada; Guang-Yu Yang; Noam Zevit; Marc E Rothenberg; Glenn T Furuta; Seema S Aceves Journal: Clin Gastroenterol Hepatol Date: 2022-02-16 Impact factor: 13.576
Authors: Marc E Rothenberg; Shawna K B Hottinger; Nirmala Gonsalves; Glenn T Furuta; Margaret H Collins; Nicholas J Talley; Kathryn Peterson; Calies Menard-Katcher; Macie Smith; Ikuo Hirano; Robert M Genta; Mirna Chehade; Sandeep K Gupta; Jonathan M Spergel; Seema S Aceves; Evan S Dellon Journal: J Allergy Clin Immunol Date: 2021-12-22 Impact factor: 10.793