Proposed Topic (Most preferred): :
Clinical Safety and Quality Service II (Projects aiming to enhance clinical safety and outcomes, clinical governance / risk management)
Proposed Topic (Second preferred): :
HA Young Investigators Session (Projects to be presented by HA staff who had joined HA for 10 years or less)
Authors (including presenting author) :
Li HL(1), Poon WT(2), Fan SY(1), Liu HK(1)
Affiliation :
(1) Department of Pharmacy, PYNEH, (2) Department of Clinical Pathology
Introduction :
Patients on thiopurines are at higher risk of leukopenia if they possess Thiopurine S-methyl transferase (TPMT)/nudix (nucleoside diphosphate linked moiety X)-type motif 15 (NUDT15) variants. TPMT/NUDT15 genetic studies prior to initiation of thiopurines may reduce the incidence of leukopenia.
Objectives :
The primary aim of the study was to investigate the effectiveness of the TPMT/NUDT15 genetic study before the initiation of thiopurines in reducing leukopenia risk in patients with Ulcerative Colitis (UC), Crohn’s Disease (CD), or Intestinal Behçet Disease (BD). Secondary aims of the study include dose dependency and time to onset of leukopenia.
Methodology :
This is a retrospective cohort study. Patients with UC, CD, or Intestinal BD who were dispensed with thiopurines from 01/01/2018 to 31/12/2022 in the Specialist Outpatient Department (SOPD) of Pamela Youde Nethersole Eastern Hospital (PYNEH) were included. Clinical data were collected, including patient demographics, thiopurine dosage, genetic study results, and incidence of leukopenia/neutropenia.
Result & Outcome :
140 patients were included in the study, and 80 (57%) had a genetic study performed. TPMT *3C heterozygous and NUDT15 p.R139C heterozygous variants are detected in 2 (2.5%) and 22 (27.5%) patients respectively. All of them are Chinese. Fifty (35.7%) patients performed a genetic study before thiopurine initiation (Group Before) and 90 (64.3%) patients either never performed or performed after thiopurine initiation (Group Never/After).
Forty (28.6%) patients developed leukopenia/neutropenia. Of these, 7 (14%) and 33 (36.7%) patients from Group Before and Group Never/After, respectively, it was statistically significant (X2 (1, N=140) = 8.092, p<0.001). The average maintenance dose of azathioprine was significantly lower in patients who developed leukopenia/neutropenia than those without (0.95mg/kg vs 1.28mg/kg, P=0.0031). The median maintenance dose was 0.84mg/kg and 1.35mg/kg, respectively. The median onset of leukopenia/neutropenia for Group Before and Group Never/After are 112 and 273 days, respectively.
In conclusion, the NUDT15 genetic variant was more common than that of TPMT in patients followed up in PYNEH. Genetic study of both NUDT15 and TPMT before initiation of thiopurines can significantly reduce thiopurines-associated leukopenia/neutropenia.
