OBJECTIVE: To assess the levels of red blood cell thiopurine methyltransferase (TPMT) in subjects with inflammatory bowel disease (IBD) and to determine how these levels impacted thiopurine dosing and leukopenia over the first six months of therapy. METHODS: A retrospective chart review was performed on all adult IBD patients (n=423, 88.2% Caucasian) who had TPMT levels measured by 11 participating gastroenterologists in Manitoba between 2008 and 2010. In addition to descriptive data, white blood cell count, dose and reason for discontinuation were analyzed for the first six months of therapy. Patients receiving ≥2.0 mg/kg of azathioprine (AZA) or ≥1.0 mg/kg of 6-mercapatopurine were considered to be 'substantially' dosed. RESULTS: Of the 423 patients, 8.3% had intermediate levels and 93.4% had normal levels of TPMT. Only one subject had a low level. A total of 216 patients had sufficient data to be included for full analysis. Patients with intermediate TPMT levels were generally started at lower doses of thiopurine than patients with normal TPMT levels (mean [± SD] 1.0±0.6 mg/kg versus 1.8±0.5 mg/kg). Of the subjects with normal TPMT levels, only 37.8% were dosed with ≥2.0 mg/kg of AZA. Each month, approximately 5% of subjects were leukopenic. These subjects received a mean overall AZA dose of 1.9±0.3 mg/kg and had a mean white blood cell count of 3.8±0.4×10(9)/L. CONCLUSIONS: Normal TPMT levels did not prevent the development of leukopenia, although life-threatening leukopenia was rare. Physicians are not using TPMT levels to substantially dose thiopurines at the outset, which may limit the speed at which adequate doses are reached to facilitate remission.
OBJECTIVE: To assess the levels of red blood cell thiopurine methyltransferase (TPMT) in subjects with inflammatory bowel disease (IBD) and to determine how these levels impacted thiopurine dosing and leukopenia over the first six months of therapy. METHODS: A retrospective chart review was performed on all adult IBDpatients (n=423, 88.2% Caucasian) who had TPMT levels measured by 11 participating gastroenterologists in Manitoba between 2008 and 2010. In addition to descriptive data, white blood cell count, dose and reason for discontinuation were analyzed for the first six months of therapy. Patients receiving ≥2.0 mg/kg of azathioprine (AZA) or ≥1.0 mg/kg of 6-mercapatopurine were considered to be 'substantially' dosed. RESULTS: Of the 423 patients, 8.3% had intermediate levels and 93.4% had normal levels of TPMT. Only one subject had a low level. A total of 216 patients had sufficient data to be included for full analysis. Patients with intermediate TPMT levels were generally started at lower doses of thiopurine than patients with normal TPMT levels (mean [± SD] 1.0±0.6 mg/kg versus 1.8±0.5 mg/kg). Of the subjects with normal TPMT levels, only 37.8% were dosed with ≥2.0 mg/kg of AZA. Each month, approximately 5% of subjects were leukopenic. These subjects received a mean overall AZA dose of 1.9±0.3 mg/kg and had a mean white blood cell count of 3.8±0.4×10(9)/L. CONCLUSIONS: Normal TPMT levels did not prevent the development of leukopenia, although life-threatening leukopenia was rare. Physicians are not using TPMT levels to substantially dose thiopurines at the outset, which may limit the speed at which adequate doses are reached to facilitate remission.
Authors: C R Yates; E Y Krynetski; T Loennechen; M Y Fessing; H L Tai; C H Pui; M V Relling; W E Evans Journal: Ann Intern Med Date: 1997-04-15 Impact factor: 25.391
Authors: Khurram J Khan; Marla C Dubinsky; Alexander C Ford; Thomas A Ullman; Nicholas J Talley; Paul Moayyedi Journal: Am J Gastroenterol Date: 2011-03-15 Impact factor: 10.864
Authors: Mattheus C B Wielenga; Jooske F van Lidth de Jeude; Sanne L Rosekrans; Alon D Levin; Monique Schukking; Geert R A M D'Haens; Jarom Heijmans; Marnix Jansen; Vanesa Muncan; Gijs R van den Brink Journal: World J Gastroenterol Date: 2014-11-28 Impact factor: 5.742
Authors: Brian Godman; Alexander E Finlayson; Parneet K Cheema; Eva Zebedin-Brandl; Inaki Gutiérrez-Ibarluzea; Jan Jones; Rickard E Malmström; Elina Asola; Christoph Baumgärtel; Marion Bennie; Iain Bishop; Anna Bucsics; Stephen Campbell; Eduardo Diogene; Alessandra Ferrario; Jurij Fürst; Kristina Garuoliene; Miguel Gomes; Katharine Harris; Alan Haycox; Harald Herholz; Krystyna Hviding; Saira Jan; Marija Kalaba; Christina Kvalheim; Ott Laius; Sven-Ake Lööv; Kamila Malinowska; Andrew Martin; Laura McCullagh; Fredrik Nilsson; Ken Paterson; Ulrich Schwabe; Gisbert Selke; Catherine Sermet; Steven Simoens; Dominik Tomek; Vera Vlahovic-Palcevski; Luka Voncina; Magdalena Wladysiuk; Menno van Woerkom; Durhane Wong-Rieger; Corrine Zara; Raghib Ali; Lars L Gustafsson Journal: BMC Med Date: 2013-08-13 Impact factor: 8.775