Mean Corpuscular Volume to White Blood Cell Ratio for Thiopurine Monitoring in Pediatric Inflammatory Bowel Disease

Objectives: Thiopurines, commonly used to treat inflammatory bowel disease (IBD), cause lymphopenia and red blood cell macrocytosis, requiring therapeutic monitoring. Mean corpuscular volume/white blood cell (MCV/WBC) ratio has been proposed as a surrogate for therapeutic monitoring. Our aim was to investigate MCV/WBC ratio for assessing clinical response to thiopurines among pediatric IBD patients. Methods: We performed a retrospective cross-sectional study at a tertiary care center using laboratory results and standardized physician global assessments (PGA) among pediatric patients taking thiopurines. Erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), fecal calprotectin, and 6-thioguanine nucleotides were assessed when available. The primary outcome was association between MCV/WBC ratio and clinical remission assessed by ESR, CRP, calprotectin, or PGA. We also used a composite outcome requiring all available data to be normal. Analyses were limited to one occurrence per patient, >60 days after starting thiopurine, and comparators were required to be within 14 days of one another. Results: 471 patients met inclusion criteria. MCV/WBC ratio poorly predicted quiescent disease as defined by PGA (area under receiver operating characteristic curve [AuROC] 0.55, 95% confidence interval [CI] 0.43–0.66). MCV/WBC ratio better predicted quiescent disease defined as normal CRP (AuROC 0.64, 95% CI 0.58–0.70) or normal ESR (AuROC 0.59, 95% CI 0.52–0.66). When the composite outcome measure was used, MCV/WBC ratio had an AuROC of 0.65 (95% CI 0.59- 0.70), indicating it is reasonably accurate in discriminating between clinical remission and active disease. Conclusions: MCV/WBC ratio is a non-inferior, easy, and low-cost alternative to thiopurine metabolite monitoring. Address correspondence and reprint requests to Jeremy Adler, 300 North Ingalls 6D18 Ann Arbor, MI 48109-5456 (e-mail: jeradler@umich.edu) Received 23 August, 2018 Accepted 28 December, 2018 Sources of support: We wish to thank Hannah K. Jary, MPH for her assistance in data management. No financial or material support was received. Conflicts of Interest and Source of Funding: All authors have no disclosures or conflicts of interest. No funding was received for this study. Authorship Statement: Jeremy Adler is the guarantor of this article. Prashanthi Kandavel and Jeremy Adler were involved in study concept and design, data collection, data analyses, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and study supervision. Sally J. Eder collected the data and critically reviewed the manuscript. Akbar K. Waljee was involved in analysis and critical revision of the manuscript. Noah E. Newman assisted in data analysis and critical revision of the manuscript. Emily P. Whitfield participated in study design and critically reviewed the manuscript. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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