Role of Thiopurines in Pediatric Inflammatory Bowel Diseases: A Real-Life Prospective Cohort Study

Ohad Atia, Oren Ledder, Tehila Ben-Moshe, Raffi Lev-Tzion, Yelana Rachmen, Esther O. Meyer, Rachel Beeri, Pinhas Renbaum, Ibrahim Shamasneh, Eyal Shteyer, Dan Turner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageAmerican English
Pages (from-to)825-832
Number of pages8
JournalJournal of Pediatric Gastroenterology and Nutrition
Issue number6
StatePublished - 1 Jun 2020

Bibliographical note

Funding Information:
O.L. received travel grant from Janssen, E.O. received consultation fee from Abbvie, and D.T. received last 3 years consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Biogen, Neopharm, Uniliver, Atlantic Health, Shire, Celgene, Lilly, Roche. The remaining authors report no conflicts of interest.

Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.


  • Crohn disease
  • azathioprine
  • children
  • mercaptopurine
  • ulcerative colitis


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