Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD) might occur at a higher incidence than current estimates suggest, according to screening data from the phase-2 ENIGMA study presented at the 2020 American College of Gastroenterology (ACG) Annual Scientific Meeting.
The trial (ClinicalTrials.gov Identifier: NCT03496571) enrolled 113 adults who were screened with a daily, validated, 8-symptom EG/EoD questionnaire to identify patients with moderate to severe symptoms. The 88 patients who met the trial’s moderate-to-severe symptom criteria underwent upper endoscopy with gastric and duodenal biopsies. The investigators collected 12 total biopsies across the gastric antrum, gastric corpus, and duodenum.
EG was histologically defined as 30 or more eos/hpf in 5 or greater hpfs. EoD was histologically defined as 30 or more eos/hpf in a minimum of 3 hpfs. Fifteen (29%) of the 51 patients with no prior history of EG/EoD were diagnosed with moderate to severe EG/EoD. Additionally, 72 of the 88 met histologic criteria for EG/EoD.
“These data suggest that EG/EoD may be more common than previously reported, and that EG/EoD should be considered in patients with chronic, moderate to severe gastrointestinal [GI] symptoms,” the study authors stated. EG/EoD is presently thought to affect 45,000 to 50,000 patients in the United States; however, this number may be “significantly underestimated and new evidence suggests it may be as common as inflammatory bowel disease (IBD),” they added.
The 72 patients who met histologic criteria for EG/EoD were randomly assigned to receive 4 monthly infusions of AK002, an investigational anti–Siglec-8 monoclonal antibody. Twenty-two patients received low-dose AK002 (a 0.3 mg/kg dose followed by 3 doses at 1.0 mg/kg); 22 patients, high-dose AK002 (a 0.3 mg/kg dose, a 1.0 mg/kg dose, and 2 concluding doses at 3.0 mg/kg); and 22 patients, placebo. Patients who completed the first phase were eligible to participate in an open-label extension analysis.
At baseline, 57 of the patients had established EG/EoD, and 15 had newly received an EG/EoD diagnosis. Most of the patients who received a new EG/EoD diagnosis had a prior history of gastroesophageal reflux/ gastroesophageal reflux disease, peptic ulcer disease, or a functional GI disorder. Patients with established EG/EoD were found to have a higher symptom intensity for loss of appetite (4.6 vs 4.4), nausea (4.2 vs 3.0), and vomiting (0.8 vs 0.4), and lower symptom intensity for diarrhea (2.4 vs 3.8) compared with patients who were newly diagnosed, respectively.
At the study’s conclusion, all patients were observed to have responded similarly to AK002, regardless of when they received their EG/EoD diagnoses. At weeks 13 to 14, 20% and 13% of patients with newly diagnosed and established disease who were treated with a placebo reported a 50% or greater improvement in symptoms compared with 67% and 64% of AK002 recipients, respectively.
At 69 to 70 weeks of therapy, 100% of patients with newly diagnosed EG/EoD and 83% of patients with established EG/EoD reported a 50% or higher improvement in symptoms after high-dose AK002 therapy.
The most common adverse event was infusion-related reaction; most reactions were mild to moderate and tended to occur on the first infusion, but not thereafter. These reactions were not observed in 20 patients in the open-label expansion cohort who received a single dose of oral prednisone the night before their infusions. There were “no other significant adverse events” reported, according to the investigators.
This study was limited by its low sample size. It remains unclear whether AK002 treatment response would remain similar in a larger cohort study.
Nevertheless, the investigators deemed AK002 a safe and potentially promising intervention for EG/EoD, and stated that “upper endoscopy with multiple gastric and duodenal biopsies may be indicated for patients with chronic, nonspecific GI symptoms.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of authors’ disclosures
Peterson KA, Genta RM, Kamboj AP, Singh B, Rasmussen HS, Dellon ES. High discovery rate of previously undiagnosed patients with eosinophilic gastritis and duodenitis using a systematic endoscopic biopsy protocol screening data analysis from ENIGMA, a randomized controlled trial. Poster presented at: American College of Gastroenterology Annual Scientific Meeting; October 26-28, 2020. P2797.