title: A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study.
abstract: OBJECTIVE
  To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs).
  
  
  METHODS
  A total of 333 participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping.
  
  
  RESULTS
  There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.59) between the two study arms. ADRs were more common in older patients (p = 0.01). There was no increase in stopping azathioprine due to ADRs in TPMT heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia.
  
  
  CONCLUSIONS
  Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas TPMT heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.
authors.affiliation: Genetic Medicine, Manchester Academic Health Science Centre (MAHSC), University of Manchester and Central Manchester NHS Foundation Trust, UK. willian.newman@manchester.ac.uk
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
authors.forename: Katherine
authors.initials: K
authors.lastname: Payne
authors.forename: Karen
authors.initials: K
authors.lastname: Tricker
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Roberts
authors.forename: Emily
authors.initials: E
authors.lastname: Fargher
authors.forename: Sudeep
authors.initials: S
authors.lastname: Pushpakom
authors.forename: Jane E
authors.initials: JE
authors.lastname: Alder
authors.forename: Gary P
authors.initials: GP
authors.lastname: Sidgwick
authors.forename: Debbie
authors.initials: D
authors.lastname: Payne
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Elliott
authors.forename: Marco
authors.initials: M
authors.lastname: Heise
authors.forename: Robert
authors.initials: R
authors.lastname: Elles
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ramsden
authors.forename: Julie
authors.initials: J
authors.lastname: Andrews
authors.forename: J Brian
authors.initials: JB
authors.lastname: Houston
authors.forename: Faeiza
authors.initials: F
authors.lastname: Qasim
authors.forename: Jon
authors.initials: J
authors.lastname: Shaffer
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: David W
authors.initials: DW
authors.lastname: Ray
authors.forename: Ian
authors.initials: I
authors.lastname: Bruce
authors.forename: William E R
authors.initials: WE
authors.lastname: Ollier
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics / Q000517:prevention & control; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics*; D009503:Neutropenia / Q000235:genetics; D010641:Phenotype
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine