KL Kliewer et al. Lancet Gastroenterol Hepatol 2023; 8: 803–15. Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial

Background/Methods:  Benralizumab is an eosinophil-depleting monoclonal antibody that targets the interleukin-5 receptor α. This was a “single-site, randomised, double-blind, placebo-controlled, phase 2 trial at Cincinnati Children’s Hospital Medical Center (Cincinnati, OH, USA). Individuals aged 12–60 years with symptomatic, histologically active eosinophilic gastritis (peak gastric eosinophil count ≥30 eosinophils per high-power field [eos/hpf] in at least five hpfs) and blood eosinophilia (>500 eosinophils per μL [eos/μL]) were randomly assigned (1:1, block size of four) to benralizumab 30 mg or placebo.” 26 patients were enrolled.

Key findings:

• Improved eosinophil counts: Changes from baseline to week 12 were significantly greater in the benralizumab group versus the placebo group for peak gastric eosinophil counts (mean –137 eos/hpf [95% CI –186 to –88] vs –38 eos/hpf [–94 to 18]; p=0·0080)
• Patients were followed up to 88 weeks in open-label extension periods. Even though banalizumab depleted eosinophils in the blood and gastric tissue in most patients, there was minimal effect on the structural histological abnormalities, endoscopic severity, and gene expression profile compared with placebo.

My take: To improve eosinophilic gastritis will require more than targeting eosinophils. In addition, eosinophil counts are not a reliable marker for improvement in this disorder. This also suggests that eosinophil counts are not reliable as a stand-alone biomarker in other eosinophilic gastrointestinal disorders.

Related blog posts:

• Too Good To Be True: Two Lessons For Eosinophilic Esophagitis
• How many eosinophils indicate eosinophilic gastroenteritis or colitis?
• Updated Nomenclature for Eosinophilic Gastrointestinal Diseases
• Endoscopic Assessment of Eosinophilic Gastritis
• Two Studies for Eosinophiles
• New Treatment for Eosinophilic Gastritis and Duodenitis