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Azathioprine Discontinuation Up for Patients With CC Genotype

Patients with rs2814778-CC also have lower last leukocyte count and lower dosing; findings persist after adjustment for race

MONDAY, June 20, 2022 (HealthDay News) — Patients with the rs2814778-CC genotype have higher risks for azathioprine discontinuation attributed to hematopoietic toxicity, even after adjustment for race, according to a study published online June 21 in the Annals of Internal Medicine.

Alyson L. Dickson, from the Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues conducted a retrospective cohort study to examine whether rs2814778-CC was associated with azathioprine discontinuation attributed to hematopoietic toxicity among thiopurine users of White or Black race.

The researchers found that among 101 patients with the CC genotype, the rate of azathioprine discontinuation attributed to hematopoietic toxicity was 3.92 per 100 person-years compared with 1.34 per 100 person-years among the 1,365 patients with the TT or TC genotype (hazard ratio from competing-risk model, 2.92; 95 percent confidence interval [CI], 1.57 to 5.41). After adjustment for race, the risk remained significant (hazard ratio, 2.61; 95 percent CI, 1.01 to 6.71). The risk associated with race alone (hazard ratio, 2.13; 95 percent CI, 1.21 to 3.75) was abrogated after genotype adjustment (hazard ratio, 1.13; 95 percent CI, 0.48 to 2.69). Among patients with the CC genotype, last leukocyte count and dosing were significantly lower.

“The next steps for research will be to study whether specific lower leukocyte counts with the rs2814778-CC genotype are associated with greater risks for infection and, if not, whether different leukocyte thresholds are appropriate for discontinuation or dose reduction,” the authors write.

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