What is this?
Imuran and Purinethol are medications that modulate the immune system's activity, thereby reducing excessive immune response in the intestines. These medications start working after 2-4 months of administration, primarily maintaining remission rather than inducing it. The drugs are metabolized in the body into two main substances: 6TG, the active ingredient, which at high levels might lead to side effects such as reduced blood cell counts, and 6MMP, an inactive substance that could potentially cause liver function abnormalities. The levels of these substances are determined, among other factors, by an enzyme called TPMT. After initiating treatment, frequent blood tests are necessary to ensure treatment safety. It's important to emphasize that in most cases, the effectiveness of the medication in controlling the disease outweighs the risk of potential side effects. The activity of the TPMT enzyme can be tested before treatment to predict a portion of the risk for side effects.
This enzyme can be tested both genetically and through enzymatic activity assays. Genetic markers can be tested at several medical centers, although it's noted that among Jews, only a third of those with low activity will test positive for genetic markers. The enzymatic activity testing, in addition to genetics, allows for more precise identification of populations at risk for side effects. Furthermore, the enzymatic activity test (as opposed to genetics) enables the identification of patients with overly high enzyme activity, predicting cases in which the medication might not be effective and could even cause liver function impairment. After initiating treatment, the levels of the breakdown products of the medications, 6TG and 6MMP, can be tested in the blood to determine whether dosage adjustments are needed, or if the medication isn't suitable for the patient.
When is it advisable to undergo this test?
Routine TPMT testing is carried out in the United States before starting treatment with Imuran or Purinethol but is not mandatory in Israel and is not included in the health basket. In European countries, the frequency of testing varies by country – some perform it as routine, while others do it less frequently. The results help determine dosages, make optimal treatment decisions, and set the frequency of blood tests after treatment initiation. As for testing the drug levels (6TG and 6MMP levels), they can certainly be helpful in cases where there's suspicion of side effects (such as unclear liver function abnormalities, reduced blood cell counts, and various clinical symptoms like hair loss) or when the clinical impact of the medication is partial and direct assessment of active substance levels in the body is desired. The test can also identify cases where the patient isn't taking the medication regularly.
Is it reliable?
Genetic TPMT testing is reliable when positive, but not when negative (as only a third of cases with reduced enzyme activity are linked to a positive genetic response). The advantage of genetic testing is that it's not influenced by medication and can be performed even during treatment with Imuran/Purinethol (in contrast to enzymatic testing). On the other hand, the enzymatic testing for enzyme activity can identify additional populations at risk and high enzyme activity. It's important to note that a normal test result doesn't completely eliminate the risk of side effects, and close medical and laboratory monitoring is essential. Measurement of drug levels (6TG and 6MMP levels) is reliable when an abnormal result is obtained. In such cases, the result can be relied upon for treatment planning.