P693 Thiopurine-induced leucopenia and hair loss were inevitable in Japanese IBD patients homozygous for NUDT15 R139C : a case series
T. Naito*, Y. Kakuta, M. Onodera, T. Kimura, M. Kuroha, H. Shiga, K. Endo, K. Negoro, Y. Kinouchi, T. Shimosegawa
Tohoku University Graduate School of Medicine, Gastroenterology, Sendai, Japan
Azathioprine (AZA) and its close analog 6-mercaptopurine (6-MP) are thiopurines widely used in the treatment of patients with inflammatory bowel diseases (IBD). Almost 10% of patients with IBD develop side effects during thiopurine treatment. The most potentially serious side effect is leucopenia. In a recent report, NUDT15 R139C was strongly associated with thiopurine-induced leucopenia in Koreans. However, there have been no reports that investigated the association between side effects including leucopenia and R139C in Japanese. Here we investigated the side effects of thiopurine-treated Japanese IBD patients who were homozygous for NUDT15 R139C.
A total of 300 Japanese IBD patients at Tohoku University Hospital who had histories of thiopurine treatment were examined. Written informed consent was obtained from all patients. NUDT15 R139C genotyping was performed using TaqMan assay. We investigated leucopenia and severe hair loss as serious adverse effects of thiopurine treatment from medical records. Leucopenia was graded by the common toxicity criteria, and severe hair loss was defined as objective hair loss, patients (especially women) may need for wearing wigs.
Five patients (four male, one female), aged 22-47 years, were homozygous for R139C. Four patients required thiopurine treatment due to Crohn's disease and the remaining patient due to IBD unclassified. The average dose of AZA was 0.93mg/kg/day (0.36-2.0). Three patients developed grade 4 leucopenia (WBC count of <1000 cells/mm3) and the remaining developed grade 3 leucopenia (WBC count of <2000 cells/mm3) within 8 weeks of commencing thiopurine therapy. Additionally, all of these patients developed severe hair loss. Although they recovered from the leucopenia and hair loss, four of five patients were treated with granulocyte-colony stimulating factor.
It was remarkable that all the Japanese patients who were homozygous for R139C developed severe leucopenia and hair loss within 8 week. The genotype frequency of R139C homozygous is approximately 1 % in Japanese. It is not frequent but not ignorable, considering the severity of leucopenia and the cosmetic problem of hair loss. Based on our case series, we should perform NUDT15 genotyping before starting thiopurine treatment and avoid thiopurine treatment in patients homozygous for NUDT15 R139C.