Dr. Cecilia Chung and associates at the Vanderbilt University’s Medical Center conducted a study published recently in MedPage Today. Results showed that patients who had inflammatory disorders, as well as the CC genotype, were more likely to discontinue or reduce doses of Imuran (azathioprine) due to blood-related (hematopoietic) toxicity.
Azathioprine is a thiopurine immunosuppressant drug that is approved to act against renal transplant rejection. Thiopurines-type medicine reduces the activity of the immune system to control inflammatory bowel disease, systemic lupus erythematosus, and other disorders.
About the Genotype of an Organism
The genotype of an organism is defined as the chemical composition of its DNA. Biologists use the term genotype to distinguish from phenotype, which consists of the observable characteristics of an organism.
This study similarly showed that patients with the CC genotype were more likely to discontinue or reduce azathioprine doses due to hematopoietic toxicities. Among Black people, that number increased threefold, and they were more likely to carry the CC genotype.
The risk doubles for patients who are prescribed azathioprine and have genetic variants such as NUDT15 or TPMT. However, the team found that the majority of patients who discontinued the drug did not carry these variants.
Dr. Chung and her associates analyzed data from Vanderbilt’s biobank of 1,466 patients diagnosed with inflammatory conditions. One hundred one patients had the CC genotype and 1,365 patients had the TT or TC genotype.
This study involved 165 Black patients and 1,301 white patients with IBD, vasculitis, rheumatoid arthritis, and various connective tissue diseases at an average of forty-four years of age.
The CC genotype was rarely found among whites. Those that did have the CC genotype were usually younger, had systemic lupus erythematosus, and had lower leukocyte counts. There were no substantive differences among the genotype groups.
At the 20.7-month follow-up after adjusting for race, the risk of discontinuing azathioprine due to hematopoietic toxicity (liver damage) remained high.
Dr. Chung and colleagues emphasized that the standard cell counts physicians use for decisions on azathioprine are primarily based on values gathered from white people. As a result, Black patients are put at risk through inappropriate dosing decisions and discontinuing treatment unnecessarily.
About Children’s Oncology
A group of 94 Black children diagnosed with acute lymphoblastic leukemia participated in a similar trial called the Children’s Oncology Group trial. That trial confirmed the findings of Dr. Chung’s team regarding lower dosing among the CC genotype group compared against the TC or TT genotype.
Dr. Chung’s team recommended that before initiation of azathioprine Duffy-null [CC] phenotype testing should take place. It should also be used when leukopenia is suspected during the administration of azathioprine.