Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Predictors of Histologic Response using Antibodies Against Interleukin-5 in Eosinophilic Esophagitis
Vivli Data Request: 7817
Funding Source: None
Potential Conflicts of Interest: Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, Lupin and Ferring. None of the listed conflicts of interest are aware of or are involved in this research.
Summary of the Proposed Research:
Eosinophilic Esophagitis is a chronic immune condition of the esophagus characterized by inflammation and the presence of eosinophils (a type of white blood cell) in the esophagus. Eosinophilia is defined as an elevated number of eosinophils which results in inflammation. The typical onset of this disease occurs in childhood, with symptoms that vary depending on the age of onset. Severity of disease is evaluated based on features from endoscopy and histologic findings from biopsies obtained from endoscopy. Histology is the study of cells and tissue as they appear under a microscope. Treatments for eosinophilic esophagitis include topical steroids (used to treat many inflammatory conditions) and proton pump inhibitors (a group of medications that reduce acid production from cells that line the stomach), although few studies have been done prospectively in children. A recent study evaluated predictors of histologic response to steroid therapy among adult patients and identified baseline dilation was identified as the only predictor of histologic response to steroid treatment. Interleukin-5 (IL-5) is a protein produced by the immune system which are known to play a key role in allergic conditions. Anti IL-5 monoclonal antibody drugs reduce the effect of IL-5. However, it is unclear what factors may influence histologic response to anti-IL-5 therapy in pediatric patients. Therefore, this study aims to evaluate baseline clinical, histologic, and endoscopic predictors of histologic response among pediatric patients using data from a clinical trial evaluating mepolizumab (an anti-IL-5) for the treatment of eosinophilic esophagitis.
Given the importance of histologic features of disease in eosinophilic esophagitis, patients may benefit from the knowledge generated from this study as it may optimize treatment and disease management. For example, esophagogastroduodenoscopy (EGD) is a type of endoscopic procedure that allows physicians to evaluate the esophagus, stomach and part of the small intestine. EGDs are an invasive procedure and understanding potential predictors of response could potentially reduce the frequency of this procedure.
Statistical Analysis Plan:
In NCT00358449, a total of 59 patients were randomized and received mepolizumab, of which 58 received all three infusions. Patients with missing histologic data will be excluded from the primary analysis. However, if analyses are statistically infeasible, analyses will be performed on an intention-to-treat basis (i.e. patients with missing outcome data will be assumed to not have achieved histologic response).
Logistic regression will used to assess the relationship between baseline predictors and histologic response. Univariate analyses will be used to identify associations between predictors and histologic response. Variables with a p-value < 0.10 will be included in the multivariate model.
Continuous variables will be presented as means (and standard deviations [SD] or as medians and interquartile ranges [IQR]) in the case of skewed data. Dichotomous variables will be presented as proportions or percentages. Descriptive statistics will be used to summarize baseline characteristics of the study population, disease characteristics and outcomes of included patients. Differences between groups will be compared using the Mann-Whitney U test or the Chi-squared test. Data will be analyzed using Stata, which is available on the Vivli platform.
A Randomized, Double-blind, Parallel Group Clinical Trial to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Mepolizumab (SB240563)(0.55mg/kg, 2.5mg/kg or 10mg/kg) in Pediatric Subjects With Eosinophilic Esophagitis, Aged 2 to 17 Years (Study MEE103219)
Data Contributor: GlaxoSmithKline
Study ID: NCT00358449
Sponsor ID: MEE103219
Wong, E.C., Gleave, A.L., Marshall, J.K. and Narula, N., Predictors of histologic response to mepolizumab in pediatric eosinophilic esophagitis. European Journal of Gastroenterology & Hepatology, pp.10-1097. Doi: 10.1097/MEG.0000000000002623