Influence of NUDT15 Genotyping on Dose Intensity of Thiopurine Administration and Long-Term Clinical Outcomes

The study evaluated the long-term effects of NUDT15 genotyping on thiopurine dosage and clinical outcomes in patients with ulcerative colitis (130 cases) and Crohn’s disease (55 cases) over a median period of 7.8 years. Patients with NUDT15 mutations (n = 48) required lower daily thiopurine dosages and had shorter times to dose reduction and discontinuation compared to the wild-type group (n = 137). The mutation group also had a higher tendency for hospitalizations and significantly more surgeries. In ulcerative colitis, discontinuation of thiopurines was linked to increased hospitalization and surgery risks. In Crohn's disease, NUDT15 SNPs were directly associated with higher hospitalization and surgery rates. The findings highlight the importance of personalized thiopurine dosing to improve long-term outcomes in these patients.