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M. J. Coenen,1 D. J. de Jong,1 C. J. van Marrewijk,1 L. J. Derijks,2 S. H. Vermeulen,1 D. R. Wong,3 O. H. Klungel,4 A. L. Verbeek,1 P. Hooymans,3 W. H. Peters,1 R. H. te Morsche,1 TOPIC recruitment team, W. G. Newman,5 H. Scheffer,1 H. Guchelaar,6 B. Franke1; 1Radboudumc, Nijmegen, Netherlands, 2Máxima Medical Centre, Verldhoven, Netherlands, 3Orbis Medical Centre, Sittard-Geleen, Netherlands, 4Utrecht University, Utrecht, Netherlands, 5University of Manchester, Manchester, United Kingdom, 6Leiden University Medical Center, Leiden, Netherlands

BACKGROUND: Over 20% of inflammatory bowel disease (IBD) patients discontinue thiopurine therapy due to severe adverse drug reactions; leucopenia is one of the most serious. Thiopurine S methyltransferase (TPMT) pharmacogenetic testing can be used to optimize thiopurine safety and efficacy. In clinical practice it is only used on a limited scale.
METHODS: We performed a randomized controlled trial with 769 IBD patients starting on thiopurines. Patients were randomly assigned to standard treatment (control) or pre-treatment screening (intervention) for three common TPMT variants (*2, *3A and *3C); patients heterozygous for a TPMT variant received 50% of the standard thiopurine dose, and patients homozygous for the variants 0-10%. Intervention and control groups were compared for leucopenia occurrence (leucocyte count <3.0*109/l) in the first 5 months after treatment initiation. Cost-effectiveness analysis included complete cases (outcome (EQ5D) and self-reported costs).
RESULTS: Thirty-nine (9.8%) patients in the intervention and 35 (9.5%) in the control group carried a TPMT variant. Among TPMT variant carriers, leucopenia occurrence was significantly reduced in the intervention compared to the control group (2.6% versus 22.9%, RR 0.11, 95%CI=0.01-0.85). Overall, no difference in leucopenia occurrence was observed between the intervention and control group (7.3% vs. 7.8%). Treatment efficacy (∆EQ5D) was similar for both study arms. Average costs (direct medical and indirect costs) were lower for patients in the intervention (n=238) compared to controls (n=216): €4433 vs. €6150, p=0.023.
CONCLUSION: Prior-to-treatment TPMT screening reduces leucopenia risk in IBD patients treated with thiopurines without impeding treatment efficacy and results in cost savings.