Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn's disease

Background & Aims: Azathioprine is effective for Crohn's disease but acts s lowly. A loading dose may decrease the time to response, Methods: A placebo -controlled study was conducted in patients with active Crohn's disease des pite prednisone treatment, Patients were randomized to a 36-hour infusion o f; 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, define d by discontinuation of prednisone and a Crohn's Disease Activity Index of less than or equal to 50 points, Erythrocyte concentrations of the azathiop rine active metabolite, 6-thioguanine nucleotide, were measured. Results: A t week 8, 13 patients (25%) were in complete remission in the azathioprine- loaded group compared with 11 patients (24%) in the placebo group, The freq uency of complete remission did not increase after 8 weeks in either group. Both groups achieved steady state of 6-thioguanine nucleotide by week 2, a nd no differences were found in mean concentrations between the groups, The re were no significant differences in the frequency of adverse events betwe en the groups. Conclusions: A loading dose does not decrease the time to re sponse in patients with steroid-treated Crohn's disease beginning azathiopr ine therapy, Steady state of erythrocyte 6-thioguanine nucleotide and compl ete response occurred earlier than previously reported.