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Insufficient Evidence for Pretesting TPMT Status

Low thiopurine S-methyltransferase enzyme activity linked to leukopenia and myelotoxicity

WEDNESDAY, June 22 (HealthDay News) -- There is insufficient evidence to support pretesting for thiopurine S-methyltransferase (TPMT) status before initiating thiopurine treatment, and estimates of the sensitivity of genotyping are imprecise, according to a review published in the June 21 issue of the Annals of Internal Medicine.

Ronald A. Booth, Ph.D., from the Ottawa Hospital Research Institute, and colleagues reviewed available literature to assess the sensitivity and specificity of TPMT genotyping for TPMT enzymatic activity, pretesting to reduce harm from thiopurine treatment, and the correlation between thiopurine toxicity and TPMT status in adults and children with chronic inflammatory diseases. Data were extracted from 54 observational studies and one randomized controlled trial, from six electronic databases.

The investigators found that available studies did not have sufficient evidence to address the effectiveness of TPMT pretesting. Genotyping sensitivity for identification of patients with low or intermediate enzymatic activity varied between 70.33 and 86.15 percent. Data to estimate genotype sensitivity for identifying patients with low to absent enzymatic activity were insufficient, though genotyping specificity approached 100 percent. Compared with noncarriers, both heterozygous and homozygous genotypes were significantly correlated with leukopenia. Low TPMT activity, but not intermediate or normal activity, was significantly correlated with myelotoxicity and leukopenia.

"The utility of pretesting for TPMT status before initiating thiopurine treatment remains in question, because insufficient evidence demonstrates that this strategy is effective to reduce harm or is superior to the established clinical standard of hematologic monitoring," the authors write.

Several of the study authors disclosed financial ties to the pharmaceutical industry.

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