Clinical predictors of thiopurine-related adverse events in Crohn's disease

Abstract

Thiopurine withdrawal due to adverse events is commoner in women over the age of 40 at prescription. These findings need to be replicated in other cohorts.

NUDT15 polymorphisms are better than thiopurine S‐methyltransferase as predictor of risk for thiopurine‐induced leukopenia in Chinese patients with Crohn's disease

“…Females were at a higher risk of leukopenia than males ( P = 0.0006; OR = 2.32; 95% CI, 1.27–4.24). Similar findings have been previously described in the researches, which could possibly be explained by recent data showing a significantly lower TPMT activity in females as compared with males . Meanwhile, drug clearance in general is lower in females and tends to decrease with age in both genders, which is the most likely explanation for these findings.…”

Mercaptopurine and inflammatory bowel disease: the other thiopurine

“…On the other hand, patients with more aggressive phenotypes (stenosing, fistulising) whose frequency increases with a longer course of the disease (21) seem to tolerate better the treatment with MP, although a larger sample size would be needed to confirm this. Some authors have described an increased risk of adverse effects with thiopurines in female patients (18,22), which was not observed in our series.…”

Increased risk of thiopurine‐related adverse events in elderly patients with IBD

“…Both renal and hepatic clearance are reduced with age, and in females compared with males, leading to higher blood concentrations of drugs and their metabolites. Interestingly, Moran et al in a small, retrospective, Canadian cohort already described that females over 40 years of age presented a higher risk of thiopurine‐related AEs. Similarly, in one of the early ENEIDA studies with the largest cohort addressing thiopurine safety profile, female gender was also a risk factor for developing nausea and myelotoxicity.…”

“…It has also been shown that the risk of opportunistic or serious infections is higher in elderly patients under immunosuppressive therapy . Although some studies have reported an increasing rate of thiopurine‐related AEs with age among female patients with Crohn's disease, no studies have specifically assessed the safety profile of thiopurines in elderly patients. Our aim was to evaluate the prevalence of non‐infectious, non‐neoplastic, thiopurine‐related AEs in those IBD patients who started on these drugs when over 60 years of age.…”