Azathioprine: Specific Genotype Linked to Treatment Discontinuation Due to Toxicity

According to a story from Medpage Today, patients using the drug azathioprine who carried a certain genotype were three times more likely to need to either cease treatment or reduce their dose of the drug due to hematopoietic toxicity. The genotype, designated the CC phenotype of variant rs2814778, is most often found among Black people. This conclusion was found through a retrospective study of 1,466 patients.

About Azathioprine

Azathioprine is an immunosuppressive medication that is used to treat a diverse array of inflammatory conditions, such as lupus, Crohn’s disease, rheumatoid arthritis, granulomatosis with polyangiitis, and ulcerative colitis. In the study, the discontinuation rate in the CC phenotype was 3.92/100 person years versus 1.34/100 person years in other phenotypes. The study also found that CC phenotype patients had lower neutrophil and leukocyte last counts, as well as a lower final dose.

About The Study

The patients in this study were being treated for a variety of inflammatory conditions; the mean age of the patients was 44 years. The analysis was constrained to solely patients of European or African ancestry. The CC phenotype was rare in white patients, and patients with the phenotype were more likely to have lower leukocyte baseline counts, were younger in age, and were more likely to have lupus over other conditions.

Toxicity is known as a substantial limitation to the use of azathioprine, and prior studies have found that certain genetic variants (NUDT15 and TPMT) more than double the risk.

The data from this study may reveal an example of racism in the field of medicine, as the higher rates of toxicity in Black people suggest that they probably weren’t represented in azathioprine clinical trials. Furthermore, the researchers pointed out that the cell count range that is considered “normal” for making decisions related to the discontinuation of azathioprine treatment are based on values for white patients. This could put a Black patient at greater risk of receiving an improper dose of azathioprine, or of having the treatment halted for no reason. Ultimately, these factors may make the use of this medicine less safe and effective for Black people.

The scientists concluded that testing for the CC phenotype should be conducted in all patients being considered for treatment with azathioprine, or at least for patients in which leukopenia is detected during the use of the treatment.


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