Open AccessCombining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice
Author(s) -
Prathima Anandi,
Alyson L. Dickson,
QiPing Feng,
WeiQi Wei,
William D. Dupont,
Dale Plummer,
Ge Liu,
Rany Octaria,
Katherine A. Barker,
Vivian Kawai,
Kelly A. Birdwell,
Nancy J. Cox,
Adriana M. Hung,
C. Michael Stein,
Cecilia P. Chung
Publication year - 2020
Publication title -
pharmacogenomics journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.804
H-Index - 85
eISSN - 1473-1150
pISSN - 1470-269X
DOI - 10.1038/s41397-020-0163-4
Subject(s) - leukopenia , thiopurine methyltransferase , azathioprine , medicine , area under the curve , framingham risk score , gastroenterology , chemotherapy , disease
Leukopenia is a serious, frequent side effect associated with azathioprine use. Currently, we use thiopurine methyltransferase (TPMT) testing to predict leukopenia in patients taking azathioprine. We hypothesized that a risk score incorporating additional clinical and genetic variables would improve the prediction of azathioprine-associated leukopenia. In the discovery phase, we developed four risk score models: (1) age, sex, and TPMT metabolizer status; (2) model 1 plus additional clinical variables; (3) sixty candidate single nucleotide polymorphisms; and (4) model 2 plus model 3. The area under the receiver-operating-characteristic curve (AUC) of the risk scores was 0.59 (95% CI: 0.54-0.64), 0.75 (0.71-0.80), 0.66 (0.61-0.71), and 0.78 (0.74-0.82) for models 1, 2, 3, and 4, respectively. During the replication phase, models 2 and 4 (AUC = 0.64, 95% CI: 0.59-0.70 and AUC = 0.63, 95% CI: 0.58-0.69, respectively) were significant in an independent group. Compared with TPMT testing alone, additional genetic and clinical variables improve the prediction of azathioprine-associated leukopenia.