BACKGROUND & AIMS:Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response. METHODS: A placebo-controlled study was conducted in patients with active Crohn's disease despite prednisone treatment. Patients were randomized to a 36-hour infusion of azathioprine, 40 mg/kg (51 patients), or placebo (45 patients) followed by oral azathioprine, 2 mg/kg, for 16 weeks. Prednisone was tapered over 5 weeks. The primary outcome measure was complete remission at week 8, defined by discontinuation of prednisone and a Crohn's Disease Activity Index of </=150 points. Erythrocyte concentrations of the azathioprine active metabolite, 6-thioguanine nucleotide, were measured. RESULTS: At week 8, 13 patients (25%) were in complete remission in the azathioprine-loaded group compared with 11 patients (24%) in the placebo group. The frequency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, and no differences were found in mean concentrations between the groups. There were no significant differences in the frequency of adverse events between the groups. CONCLUSIONS: A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte6-thioguanine nucleotide and complete response occurred earlier than previously reported.
RCT Entities:
BACKGROUND & AIMS:Azathioprine is effective for Crohn's disease but acts slowly. A loading dose may decrease the time to response. METHODS: A placebo-controlled study was conducted in patients with active Crohn's disease despite prednisone treatment. Patients were randomized to a 36-hour infusion of azathioprine, 40 mg/kg (51 patients), or placebo (45 patients) followed by oral azathioprine, 2 mg/kg, for 16 weeks. Prednisone was tapered over 5 weeks. The primary outcome measure was complete remission at week 8, defined by discontinuation of prednisone and a Crohn's Disease Activity Index of </=150 points. Erythrocyte concentrations of the azathioprine active metabolite, 6-thioguanine nucleotide, were measured. RESULTS: At week 8, 13 patients (25%) were in complete remission in the azathioprine-loaded group compared with 11 patients (24%) in the placebo group. The frequency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, and no differences were found in mean concentrations between the groups. There were no significant differences in the frequency of adverse events between the groups. CONCLUSIONS: A loading dose does not decrease the time to response in patients with steroid-treated Crohn's disease beginning azathioprine therapy. Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported.
Authors: P W Lowry; C L Franklin; A L Weaver; M G Pike; D C Mays; W J Tremaine; J J Lipsky; W J Sandborn Journal: Gut Date: 2001-11 Impact factor: 23.059
Authors: S P L Travis; E F Stange; M Lémann; T Oresland; Y Chowers; A Forbes; G D'Haens; G Kitis; A Cortot; C Prantera; P Marteau; J-F Colombel; P Gionchetti; Y Bouhnik; E Tiret; J Kroesen; M Starlinger; N J Mortensen Journal: Gut Date: 2006-03 Impact factor: 23.059
Authors: P W Lowry; C L Franklin; A L Weaver; C L Szumlanski; D C Mays; E V Loftus; W J Tremaine; J J Lipsky; R M Weinshilboum; W J Sandborn Journal: Gut Date: 2001-11 Impact factor: 23.059
Authors: Martin H Holtmann; Frank Krummenauer; Christina Claas; Kristina Kremeyer; Dirk Lorenz; Olivia Rainer; Iris Vogel; Ulrich Böcker; Stephan Böhm; Carsten Büning; Rainer Duchmann; Guido Gerken; Hans Herfarth; Norbert Lügering; Wolfgang Kruis; Max Reinshagen; Jan Schmidt; Andreas Stallmach; Jürgen Stein; Andreas Sturm; Peter R Galle; Daan W Hommes; Geert D'Haens; Paul Rutgeerts; Markus F Neurath Journal: Dig Dis Sci Date: 2009-06-10 Impact factor: 3.199