Thiopurines in IBD
 • Steroid-sparing ...

Thiopurines in IBD


 • Steroid-sparing agents indicated for maintenance of remission in UC and CD

 • Not induction agents. Slow onset of action (~12 weeks)

 • In combination with aTNF -> increase aTNF levels and decrease Ab formation -> better outcomes


 • Thiopurine S-methyltransferase (TPMT)

 • 6-TGN: active metabolite. Associated to drug efficacy and Bone Marrow toxicity

 • 6-MMP: inactive metabolite. Associated to Hepatotoxicity

 • "Shunters" or "Hypermethylators": preferentially metabolyze 6MP towards 6-MMP


 • Based on TPMT activity. NUDT15 gene mutations associated to leukopenia (Asian populations)

 • Homozygous low activity: avoid thiopurines. Highest risk for severe and fatal myelosupression

 • Heterozygous or intermediate activity: decrease dose by 50%

 • Homozygous high or normal activity: AZA 2-3mg/kg and MP 1-1.5mg/kg

TDM (thiopurine metabolites):

 • 4 to 6 weeks after start and after dose changes/allopurinol addition

 • Reactive

 • when determination of compliance is needed

 • 6TG 235-450 associated to good clinical response. 

     - low 6TG/low 6MMP: increase dose by 25-50mg. 

     - low 6TG/high 6MMP ("shunter"): decrease dose by 25% and add allopurinol 100mg qd or

dose splitting

     - Absent or minimal 6TG and 6MMP: non-compliant. 

     - High 6TG and not responding: 

     - switch MOA. 6TG> 125 may be adequate to achieve good levels of IFX.


 • Serious Infections: lower rate when compared to aTNF. (*But less effective drugs). GI intolerance. Pancreatitis (dose-independent, 3%)

 • Bone marrow toxicity: linked to high 6TG>400. Monitor CBC q 1-2 weeks initially and then q3m

 • Hepatotoxicity: linked to high 6MMP > 5700

 • NMSC. Lymphomas are ↑ but uncommon (>aTNF). Risk becomes ↑ after 1y of exposure. Absolute risk ↑ > 50yo. HSTC lymphoma (potentially fatal): men < 35 yo on Rx > 2y are at ↑ risk. EBV seroconversion is a concern-most adults already EBV+

Dr. Jean Donet @JeanDonet

#Thiopurines #IBD #Inflammatory #BowelDisease #Management #Treatment
Contributed by

Dr. Gerald Diaz
Board Certified Internal Medicine Hospitalist, GrepMed Editor in Chief 🇵🇭 🇺🇸 - Sign up for an account to like, bookmark and upload images to contribute to our community platform. Follow us on IG: | Twitter:

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