Benralizumab (anti-IL5Rα) depletes gut tissue eosinophilia and improves symptoms in hypereosinophilic syndrome with gastrointestinal involvement
Sunday, March 4, 2018: 4:30 PM
South Hall A2 (Convention Center)
Fei Li Kuang, MD PhD, Hawaa Alao, Sheila Kumar, Astin Powers, Martha Quezado, Zengfeng Wang, JeanAnne Ware, Lauren Wetzler, Thomas Brown, Paneez Khoury, MD FAAAAI, Amy D. Klion, MD
RATIONALE: Hypereosinophilic syndrome (HES) with gastrointestinal (GI) involvement is defined by clinical symptoms, marked GI eosinophilia and a peripheral eosinophil count (AEC) ≥ 1500 cells/mm3. Although some patients respond to corticosteroids or dietary intervention, many are treatment-refractory or intolerant. The efficacy of eosinophil-targeted therapies, including benralizumab (anti-IL5Rα), is unknown in this patient population.

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.