Mepolizumab in the treatment of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a clinical entity characterized by eosinophilic infi ltration limited to the esophageal epithelium without signifi cant eosinophilic infl ammation of the remainder of the upper gastrointestinal tract mucosa. It can occur in isolation or as part of an atopic spectrum together with asthma, allergic rhinitis and/or atopic dermatitis. EE was fi rst described in the literature in the 1970s [1,2]. The healthy esophageal epithelium is devoid of eosinophils. In 1982, Winter et al. reported that mild eosinophilic infl ammation of the esophagus is indicative of gastroesophageal ref lux disease (GERD) [3]. A retrospective study by Attwood and colleagues [4], published in 1993, showed that the presence of high concentrations of eosinophils in esophageal biopsies from patients with dysphagia, normal endoscopy and normal 24-h esophageal pH monitoring represented a distinctive clinicopathologic syndrome. This observation was further elucidated by Kelly et al. in 1995, with resultant increasing awareness of EE [5]. Presently, EE is defi ned as a primary disorder of the esophagus, characterized by esophageal and/or upper gastrointestinal tract symptoms in association with esophageal mucosal biopsy specimens containing 15 or more intraepithelial eosinophils per high power fi eld in one or more fi elds and in the absence of pathologic GERD as evidenced by a normal pH monitoring study of the distal esophagus or lack of response to acid-suppressive therapy [6]. Recent data appears to challenge this defi nition with the possibility of GERD coexisting with EE in a subset of patients [7,8]. While the epidemiology of EE remains to be extensively studied, it has been reported in several countries. In the USA, a national pathology database was used to identify EE cases from a cohort of 74,162 patients undergoing esophagogastroduodenoscopies (EGDs) in 26 states; 363 cases of EE were identifi ed, with all age groups being represented [9]. In addition to its widespread occurrence, EE appears to have an accelerating incidence that cannot be fully accounted for by increased recognition. A large population-based study using a single institution’s pathology database in Hamilton County, OH, USA, found 103 children with EE [10]. Of these, only three patients (2.8%) were identifi ed prior to the year 2000. The overall incidence per 10,000 population was estimated to be 1.28 in 2003, suggesting a 0.37 (29%) increase in the frequency from 2000 [10]. Another population-based study conducted in Olmsted County, MN, USA, over a period of 30 years estimated the prevalence of EE in 2007 to be 10.4 per 10,000 population [11]. A male predominance with a male:female ratio of 2:1 has been reported in both pediatric and adult Mepolizumab is a humanized monoclonal antibody that binds specifi cally to and inactivates a protein cell messenger termed IL-5, which plays a major role in the proliferation, maturation, activation and survival of eosinophils. As a result, mepolizumab has been studied in a number of eosinophil-associated diseases, such as asthma, hypereosinophilic syndrome and eosinophilic esophagitis (EE). EE is a clinical entity characterized by eosinophilic infi ltration of the esophagus (≥15 eosinophils/high power fi eld in one or more fi elds) in the absence of gastroesophageal refl ux. EE is on the rise, and this can not be fully accounted for by increased recognition. Currently, available therapies, although successful in many cases, can be disappointing in some patients, whether from lack of response, negative impact on quality of life, or signifi cant toxicity. In order to better defi ne EE therapy, investigators are evaluating novel drugs, including anti-IL-5 agents such as mepolizumab. Mepolizumab has been demonstrated to signifi cantly reduce mean blood and tissue eosinophil count. It is well-tolerated and no drug-related serious adverse events have been described in the published literature to date. Mepolizumab is currently under clinical investigation and is not yet available for general use.