COPENHAGEN — Initial treatment with infliximab plus azathioprine in patients with moderate to severe Crohn's disease led to more remissions than did a standard approach that started with topical or systemic steroid treatment, in a study with 129 patients.
“Steroids are not necessary for treating Crohn's disease,” said Geert D'Haens, M.D., at the 13th United European Gastroenterology Week.
“Our results strongly suggest that infliximab plus azathioprine, but without a steroid, is a superior regimen for moderate to severe, newly diagnosed Crohn's disease,” said Dr. D'Haens, a gastroenterologist at Imelda Hospital in Bonheiden, Belgium. Further studies must compare various strategies to identify the best way to use biologic therapy to induce and maintain remission, he added.
The two management strategies were compared at 26 centers in Belgium and the Netherlands. The study enrolled patients with newly diagnosed Crohn's disease, a disease activity index of more than 220, and no prior treatment with a steroid or immunomodulator.
The study was sponsored by Centocor and Schering-Plough. Centocor markets infliximab (Remicade) in the United States, and Schering-Plough markets the drug in all other countries. Dr. D'Haens has served as a consultant and speaker for both companies.
The 65 patients in one group were randomized to treatment that started with three infusions of infliximab at weeks 0, 2, and 6, and daily treatment with 2–2.5 mg/kg azathioprine. Patients in this group who relapsed received another infusion of infliximab, and if they relapsed again they were treated with a steroid.
The remaining 64 patients were randomized to start treatment with either topical budesonide or oral prednisone, at a daily dose of 40 mg. Patients in this group who relapsed were again treated with a steroid plus azathioprine. If they relapsed a second time, they were treated with a three-dose course of infliximab.
The study's primary end point was the rate of remission at 6 and 12 months after starting treatment. Remission was defined as having a Crohn's disease activity index of less than 150, with no ongoing need for steroid treatment and no surgical resection.
After 6 months, the remission rate was 60% in the infliximab-first group and 41% among the patients who received steroid treatment first, a statistically significant difference, reported Dr. D'Haens.
After 12 months, the remission rate was 61% in the infliximab-first group and 50% among the steroid-first group, a difference that was not statistically significant.
Among patients in the infliximab-first group, 59% required no additional infliximab treatment beyond their initial three doses during the year of follow-up. In the steroid-first group, 62% of patients also required treatment with azathioprine.
The study also used a new measure of efficacy, the rate of overall treatment success. This measure tracked the number of patients who reached and maintained a remission after 14, 26, 39, and 52 weeks of treatment. This end point was reached by 29% of patients in the infliximab-first group and 5% of those treated with a steroid first, a statistically significant difference.
After the first 6 months of treatment, none of the patients in the infliximab-first group were on steroid treatment, while 31% in the steroid-first were on systemic prednisone.
After 12 months, no patients in the infliximab-first group were on steroid treatment, compared with 17% in the steroid-first group. Nine patients in the infliximab-first group had a serious adverse event that led to withdrawal from treatment, compared with 10 patients in the steroid-first group.