Azathioprine Discontinuation linked to CC genotype and hematopoietic toxicity


eMediNexus    22 June 2022

Annals of Internal Medicine reported a study which stated that patients with inflammatory diseases who have the CC genotype are more likely to stop taking azathioprine (Imuran) due to hematological toxicity and require dose reductions for thiopurine dosages.

Azathioprine is a thiopurine immunosuppressant medication that is used to prevent kidney transplant rejection and active rheumatoid arthritis. Irritable bowel disease (IBD), systemic lupus erythematosus (SLE), and other disorders can be treated with it.

Around 1400 individuals with IBD (18-35 percent), SLE (10-25 percent), rheumatoid arthritis, vasculitis, or other connective tissue illnesses who contained the CC genotype of variant rs2814778 were included in the study. When compared to TT or TC genotype carriers, they had nearly three times the risk of quitting azathioprine due to haematological toxicity (HR 2.92, 95 percent CI 1.57-5.41). Patients prescribed azathioprine who have particular genetic variants (TPMT or NUDT15) have a greater risk of haematological toxicity, albeit most patients who stop taking it do not have such variants.

The CC genotype had 3.92 per 100 person-years of azathioprine discontinuation compared to 1.34 per 100 person-years for the TT or TC genotypes. After adjusting for the race, the risk remained considerable (HR, 2.61 [CI, 1.01 to 6.71]). Adjusting for genotype eliminated the risk associated with race alone (HR, 2.13 [CI, 1.21 to 3.75]). (HR, 1.13 [CI, 0.48 to 2.69]). Patients with the CC genotype had a lower final leukocyte count and required less medication. They also required lower thiopurine 6-mercaptopurine (6-MP) dose as compared to the target daily dose of 75 mg/m2 (median, 0.83 [IQR, 0.70 to 0.94] for the CC genotype vs. 0.94 [IQR, 0.72 to 1.13] for the TT or TC genotype; P = 0.013). (MedPage Today June 20, 2022) 

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