A Pilot Study of Omalizumab in Eosinophilic Esophagitis

Abstract

Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE) levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy.Trial RegistrationClinicalTrials.gov NCT01040598

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity

“…The positive predictive values for causative food identified by SPT ranged from 26% to 96%, with an average of 47% (16). Based on the assumption that IgE plays a key role in pathogenesis, a therapy with an antiIgE antibody for 12 weeks in pediatric and adult patients with EoE was initiated in a non-placebo-controlled study resulting in a remission rate of only 33% despite an effective reduction of IgE levels observed in the esophageal tissue (20). In a double-blind placebo-controlled study, anti-IgE treatment was not better than placebo in inducing EoE remission (21).…”

Systematic review of histological remission criteria in eosinophilic esophagitis

“…Among the interventional trials (randomized controlled trial studies [RCTs] or trials with historical controls), 80 (80%) compared treatment effect using histological remission as values within the range of 0 to ≤5 eosinophils/hpf. Among studies that examined the effectiveness of monoclonal antibody treatment in EoE subjects, 80% defined histological remission as peak esophageal eosinophil counts within the range of 0 to ≤5 24, 25, 26, 27, 28. Approximately 26% (N = 15) of the eligible studies examined remission among EoE patients who received only the diet elimination treatment formula (SFED, FFGED, ELED) compared to other forms of treatment, with the most common definitions falling within 0 to ≤5 eosinophils/hpf 29, 30, 31, 32, 33, 34 or 11 to ≤15 eosinophils/hpf 35, 36, 37, 38, 39, 40.…”

Eosinophilic esophagitis

“…Another class of antibodies against IgE (omalizumab) also did not show any histological or symptomatic improvement. 105 These agents are therefore not recommended for use in EoE. A small case series of anti TNF antibodies in EoE also did not show any benefit.…”