Open AccessRole of Thiopurines in Pediatric Inflammatory Bowel Diseases
Author(s) -
Atia Ohad,
Ledder Oren,
BenMoshe Tehila,
LevTzion Raffi,
Rachmen Yelana,
Meyer Esther O.,
Beeri Rachel,
Renbaum Pinhas,
Shamasneh Ibrahim,
Shteyer Eyal,
Turner Dan
Publication year - 2020
Publication title -
journal of pediatric gastroenterology and nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 131
eISSN - 1536-4801
pISSN - 0277-2116
DOI - 10.1097/mpg.0000000000002566
Subject(s) - medicine , thiopurine methyltransferase , erythrocyte sedimentation rate , ulcerative colitis , gastroenterology , inflammatory bowel disease , white blood cell , prospective cohort study , adverse effect , mean corpuscular volume , therapeutic drug monitoring , absolute neutrophil count , toxicity , disease , pharmacokinetics , hematocrit , neutropenia
Objectives: Use of thiopurines for inflammatory bowel diseases (IBDs) is declining in some parts of the world. We aimed to explore outcomes of thiopurines and predictors of response in a real‐world prospective cohort of children with dose optimization. Methods: Children with IBD treated with thiopurines without biologics were enrolled. Dosing was guided by thiopurine S‐methyltransferase‐activity at baseline and by clinical response and toxicity at 4 months; 1 year into the study, therapeutic drug monitoring at 4 months was also considered in the decision making. The primary outcome was steroid‐free remission without treatment escalation by 12 months (SFR), using the intention‐to‐treat approach. Results: A total of 129 children were included (74% Crohn disease [CD] and 26% ulcerative colitis [UC]). SFR was achieved in 37 (39%) CD and 13 (39%) UC patients, and SFR with normal erythrocyte sedimentation rate/C‐reactive protein in 20 (21%) and 9 (27%), respectively. At 4 months, mean corpuscular volume/white blood cell ratio and Δ absolute neutrophil count weakly correlated with 6‐thioguanine ( r = 0.33, P = 0.02 and r = 0.32, P = 0.02, respectively). In CD, SFR was associated with 4‐month median weighted Pediatric Crohn Disease Activity Index (2.5 [IQR 0–7.5] in responders vs 5 in nonresponders [0–12.5], P = 0.048) and Δabsolute neutrophil count (1.7 [IQR 0.7–4.1] vs 0.05 [−2.3–0.9]; P = 0.03). Mild drug‐related adverse events were recorded in 30 children (22%), 3 required stopping the drug. Conclusions: In this real‐life prospective cohort using dose optimization, thiopurines were safe and effective in 21% of CD and 27% of UC patients, including normalization of C‐reactive protein and erythrocyte sedimentation rate. Thiopurines remain a viable option in the treatment algorithm of mild‐moderate pediatric IBD, especially in girls whose risk for lymphoma is lower.