GASTROENTEROLOGY ARTICLE OF THE WEEK
December 15, 2005
Lichtenstein GR. Use of laboratory testing to guide 6-Mercaptopurine/Azathiprine therapy. Gastroenterology 2004;127:1558-64
1. 6MP and AZA:
a. must be cleaved by TMPT to 6-TG, the active metabolite
b. a low TPMT activity level reliably predicts myelosuppression if these individuals are treated with the usual dose of 6-MP or Aza.
c. approximately 11% of the population is heterozygote for TMPT mutations and 0.3% are homozygotes.
d. several randomized trials have demonstrated the usefulness of TMPT assay prior to starting 6-MP or AZA.
True or False
2. Patients with normal TMPT activity are not a risk of developing myelosuppression from 6-MP or AZA.
3. Starting AZA at a low dose and titrating upward achieves the same endpoint as starting at the target dose, however time to response is longer.
4. Titrating AZA levels to leukopenia correlates with improved clinical response in Crohn’s disease.
5. TMPT enzyme activity testing will only benefit the 1 in 300 patients who is homozygote for deficiency.
6. Patients who do not develop leukopenia after 6 months of therapy with AZA or 6-MP are not at risk of developing it in the future.
7. Levels of 6-TG correlate with clinical response in patients with Crohn’s disease
8. Monitoring for 6-MMP levels is a more reliable and safer way of detecting hepatotoxicity than monitoring liver enzymes levels
9. Target dose for AZA is 2.0 to 3.0 mg/kg, for 6-MP is 1.0 – 1.5mg/kg; these target doses can be used as initial therapy in patients heterozygotes for TPMT activity.