METHODS: Twenty symptomatic HES subjects on stable background therapy with persistent eosinophilia (AEC ≥1000 cells/mm3) were enrolled in a phase 2 double-blind placebo-controlled trial of benralizumab. Seven had gastrointestinal involvement and underwent upper and lower endoscopy at baseline and week 24 (after 3-6 months on active drug). Biopsies were reviewed by a single pathologist, and peak eosinophil count per high power field (eos/hpf) recorded. Anti-EPX staining was performed on selected sections. Clinical and laboratory parameters were assessed monthly.
RESULTS: Despite medical therapy (5/7) and/or dietary modification (4/7), all 7 subjects had severe symptoms with blood eosinophilia (geometric mean AEC 1619 cells/mm3; range 1000-5620/mm3). Baseline biopsies revealed eosinophilia in multiple GI segments: esophagus (4/7), stomach (6/7), duodenum (4/7) and colon (4/6). Post-treatment at week 24, AEC was 0 cells/mm3 in all subjects and endoscopies demonstrated dramatic depletion of eosinophils: median 0 eos/hpf in all upper GI segments (range 0-3 eos/hpf, n=7) and colon (range 0-1 eos/hpf, n=5). Most subjects reported improvement in their baseline GI symptoms (6/7) and two subjects attempted and were able to re-introduce previously avoided foods.
CONCLUSIONS: Benralizumab may be effective in HES with GI involvement. Larger scale clinical trials are needed to further evaluate efficacy.