PMID- 24592889
OWN - NLM
STAT- MEDLINE
DCOM- 20150519
LR  - 20220129
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 78
IP  - 3
DP  - 2014 Sep
TI  - Thiopurine monitoring in children with inflammatory bowel disease: a systematic 
      review.
PG  - 467-76
LID - 10.1111/bcp.12365 [doi]
AB  - AIMS: The aim was to systematically review the evidence on the clinical 
      usefulness of thiopurine metabolite and white blood count (WBC) monitoring in the 
      assessment of clinical outcomes in children with inflammatory bowel disease 
      (IBD). METHODS: Medline, Embase, Cochrane Central Register of controlled trials 
      and http://www.clinicaltrials.gov were screened in adherence to the PRISMA 
      statement by two independent reviewers for identification of eligible studies. 
      Eligible studies were randomized controlled trials (RCTs), cohort studies and 
      large case series of children with inflammatory bowel disease (IBD) (<18 years) 
      who underwent monitoring of thiopurine metabolites and/or WBC. RESULTS: Fifteen 
      papers were identified (n = 1026). None of the eligible studies were RCTs. High 
      6-thioguanine nucleotide (6TGN) concentrations were not consistently associated 
      with leucopenia. Leucopenia was not associated with achievement of clinical 
      remission. A positive but not consistent correlation between 6TGN and clinical 
      remission was reported. Haematological toxicity could not be reliably assessed 
      with 6TGN measurements only. A number of studies supported the use of high 
      6-methylmercaptopurine ribonucleotides (6MMPR) as an indicator of hepatotoxicity. 
      Low thiopurine metabolite concentration may be indicative of non-compliance. 
      CONCLUSION: Thiopurine metabolite testing does not safely predict clinical 
      outcome, but may facilitate toxicity surveillance and treatment optimization in 
      poor responders. Current evidence favours the combination of thiopurine 
      metabolite/WBC monitoring and clinic follow-up for prompt identification of 
      haematologic/hepatic toxicity safe dose adjustment, and treatment modification in 
      cases of suboptimal clinical outcome or non-compliance. Well designed RCTs for 
      the identification of robust surrogate markers of thiopurine efficacy and 
      toxicity are required.
CI  - (c) 2014 The British Pharmacological Society.
FAU - Konidari, Anastasia
AU  - Konidari A
AD  - Department of Clinical and Molecular Pharmacology, Wolfson Centre for 
      Personalised Medicine, Institute for Translational Medicine, University of 
      Liverpool, Liverpool, UK.
FAU - Anagnostopoulos, Antonios
AU  - Anagnostopoulos A
FAU - Bonnett, Laura J
AU  - Bonnett LJ
FAU - Pirmohamed, Munir
AU  - Pirmohamed M
FAU - El-Matary, Wael
AU  - El-Matary W
LA  - eng
GR  - MR/L006758/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Purines)
SB  - IM
MH  - Chemical and Drug Induced Liver Injury/diagnosis/etiology
MH  - Child
MH  - Drug Monitoring/methods
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/metabolism/*therapeutic use
MH  - Inflammatory Bowel Diseases/*drug therapy
MH  - Leukocyte Count
MH  - Medication Adherence
MH  - Purines/adverse effects/metabolism/*therapeutic use
MH  - Treatment Outcome
PMC - PMC4243898
OTO - NOTNLM
OT  - drug monitoring
OT  - inflammatory bowel disease
OT  - thiopurine
EDAT- 2014/03/07 06:00
MHDA- 2015/05/20 06:00
PMCR- 2015/09/01
CRDT- 2014/03/06 06:00
PHST- 2013/08/07 00:00 [received]
PHST- 2014/02/14 00:00 [accepted]
PHST- 2014/03/06 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/05/20 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - 10.1111/bcp.12365 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2014 Sep;78(3):467-76. doi: 10.1111/bcp.12365.