Food allergy, anaphylaxis, dermatology, and drug allergy
Anti–IL-5 (mepolizumab) therapy for eosinophilic esophagitis

https://doi.org/10.1016/j.jaci.2006.09.007Get rights and content

Background

Eosinophilic esophagitis (EE) is characterized by high numbers of eosinophils in the esophagus and epithelial hyperplasia, and is being increasingly recognized. IL-5 promotes eosinophil trafficking to the esophagus, and positively regulates eosinophil growth, activation, survival, and tissue recruitment.

Objective

We hypothesized that the humanized monoclonal IgG1 antibody against human IL-5 (mepolizumab) may be useful in the control of EE.

Methods

An open-label phase I/II safety and efficacy study of anti–IL-5 in 4 adult patients with EE and longstanding dysphagia and esophageal strictures was conducted. Patients received 3 infusions of anti–IL-5 (750 mg intravenously monthly) without change in their current therapy. The levels of plasma IL-5, peripheral blood eosinophils, and CCR3+ cells in blood, quality of life measurements, and histological analysis of esophageal biopsies were determined before and 1 month after treatment.

Results

Peripheral blood eosinophilia and percent of CCR3+ cells decreased by 6.4-fold and 7.9-fold (P < .05), respectively, after anti–IL-5 treatment. Notably, mean and maximal esophageal eosinophilia decreased from 46 to 6 and from 153 to 28 eosinophils/high-power field (×400; average, 8.9-fold, P < .001, and 6-fold, P < .05), respectively. Patients reported a better clinical outcome and improved quality of life (P = .03). Therapy was generally well tolerated, and responsiveness to anti–IL-5 therapy did not correlate with plasma IL-5 levels.

Conclusion

Anti–IL-5 therapy is associated with marked decreases in peripheral blood and esophageal eosinophilia (including the number of CCR3+ blood cells) in patients with EE and improved clinical outcomes.

Clinical implications

Anti–IL-5 is a promising therapeutic intervention for EE.

Section snippets

Protocol

The study was conducted with the approval of the Institutional Review Board and the Food and Drug Administration and with informed consent from patients (clinicaltrials.gov, NCT00266565). Patients with EE had >24 peak eosinophils per hpf and no other pathology in other gastrointestinal segments. Patients, sequentially recruited, were monitored (for complete blood count, physical examination) every 2 weeks for a period of 28 weeks and were also evaluated at weeks 0, 8, and 20 by pulmonary

Patient characteristics

The subjects consisted of 2 male and 2 female patients with an age range of 18 to 41 years. Sequential patients with longstanding symptoms and histological diagnosis of EE but not other EGID were selected. Patients had EE symptoms for 9 or more years before enrollment (Table I, Table II summarize the clinical and pathological characteristics of the patients with EE before and after anti–IL-5 therapy). Patient 1, briefly described in another publication,27 had a progressive dysphagia to solid

Discussion

Eosinophilic esophagitis is a global disease that has been increasingly recognized over the last decade.10, 31 On the basis of the need for more effective therapy, we aimed to assess the safety and efficacy of anti–IL-5 as a new therapy for EE. Overall, our study demonstrates that anti–IL-5 therapy was associated with improvements in clinical symptoms, quality of life, endoscopic findings (in 3 of 4 patients), peripheral blood eosinophilia (6-fold reduction), and pathological features of EE

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    Citation Excerpt :

    Both of these medications are FDA approved for eosinophilic asthma, whereas mepolizumab is also approved for eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. An initial report using mepolizumab in 4 adult patients revealed prominent decreases in both peripheral blood and esophageal tissue eosinophil levels, including improvements in clinical symptoms.25 A subsequent small randomized trial in 11 adults, using 2 doses of 750 mg intravenously and then 2 doses of 1500 mg if no initial improvement was observed, revealed a significant reduction in esophageal eosinophil levels in the active group compared with placebo (54% decrease vs 5%; P = .03) though only a nonsignificant mild improvement in symptoms.26

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Supported by grants from the Food and Drug Administration #FD-R 002313 and the Burroughs Wellcome Fund (M. E. Rothenberg), the Campaign Urging Research for Eosinophilic Diseases Foundation, and the Buckeye Foundation. M. L. Stein is a recipient of a fellowship from the American Physicians Fellowship for Medicine in Israel.

Disclosure of potential conflict of interest: M. E. Rothenberg has consultant arrangements with GlaxoSmithKline, Ception Therapeutics, Cambridge Antibody Technology, and MedaCorp; owns stock in Ception Therapeutics; has received grant support from Cambridge Antibody Technology; is on the speakers' bureau for Merck; and has received honoraria from GlaxoSmithKline, Ception Therapeutics, Merck, and Tanox. M. H. Collins and A. H. Assa'ad have consulting arrangements with and have received grant support from GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest.

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