P830 Genotype-based treatment with thiopurine reduces incidence of myelosuppression in patients with inflammatory bowel diseases
J.Y. Chang1, S.J. Park2, E.S. Jung3, S.A. Jung4, C.M. Moon5, J. Chun2, J.J. Park2, E.S. Kim6, Y. Park2, T.I. Kim2, W.H. Kim2, J.H. Cheon2
1College of Medicine- Ewha Womans University, Health Promotion Center, Seoul, Republic of Korea, 2Yonsei University College of Medicine, Internal Medicine, Seoul, Republic of Korea, 3Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea, 4Internal Medicine, College of Medicine- Ewha Womans University, Seoul, Republic of Korea, 5College of Medicine- Ewha Womans University, Internal Medicine, Seoul, Republic of Korea, 6Korea University College of Medicine, Internal Medicine, Seoul, Republic of Korea
Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pre-treatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments.
We performed a multicentre, prospective study of patients with IBD at 5 tertiary medical centres in Korea, from January 2016 through September 2018. Seventy-two patients were randomly assigned to a group that underwent genotype analysis for the NUDT15 variant (rs116855232) and FTO variant (rs79206939) and 3 common TPMT variants (rs1800460, rs1800462, rs1142345) associated with myelosuppression and 92 patients were assigned to a group that did not undergo genotype analysis (non-genotyping group). Patients heterozygous for any variant received 50 mg azathioprine equivalents, whereas those who were homozygous for any variant received alternative drugs. Patients who did not carry any of the genetic variants and patients in the non-genotyping group received 50 mg azathioprine equivalents followed by dose escalation up to 2–2.5 mg/kg. Myelosuppression was defined as white blood cell counts below 3000/μL, levels of haemoglobin 10 g/dl, or platelet counts below 100 K/μl.
Twelve patients (16.7%) in the genotype analysis group and 33 patients (35.9%) in the non-genotyping group developed myelosuppression (
In a randomised controlled study of patients undergoing thiopurine therapy for IBD, we found that selection of therapy based on genetic variants associated with thiopurine-induced leucopoenia significantly reduced the proportion of patients with myelosuppression during treatment.