WASHINGTON – More intensive treatment with early combined immunosuppression was associated with a longer time to first flare and fewer flares than conventional management during long-term follow-up of patients with Crohn’s disease.

Fewer patients treated with the “top-down” approach required anti–tumor necrosis factor (anti-TNF) agents or corticosteroids during follow-up, Dr. Daniël Hoekman reported during the annual Digestive Disease Week.

Current guidelines advocate an initial “step-up” approach for Crohn’s disease that focuses on controlling symptoms with corticosteroids followed by immunomodulators and then anti-TNF inhibitors to manage the chronic relapsing-remitting course of Crohn’s.

A new strategy has been proposed with the aim of altering the disease course and slow progression by reversing the treatment paradigm from a step-up to a top-down approach. A 2-year, randomized European trial showed that a top-down approach, combining early immunosuppression with infliximab (Remicade) and azathioprine (Imuran in Canada, Azasan in the United States) followed by azathioprine monotherapy and, if necessary, additional infliximab and corticosteroids, was more effective than step-up management for induction of remission and reduction of steroids in the short term (Lancet 2008;371:660-7).

To investigate the long-term outcome of Crohn’s disease, a retrospective chart review was performed in 119 of the 133 trial participants followed for 8 years or 16 semesters (mean 14.2 semesters) after the initial 2-year trial period. Management during the present study was left to physician discretion. At the start of the extended follow-up, most patients in both the step-up and top-down groups were on immunomodulators (66% vs. 82%) and only a small portion were using infliximab (15% vs. 20%). A total of 164 endoscopy reports were available for 59% of patients.

During follow-up, significantly more patients treated with the step-up approach than the top-down approach required anti-TNF inhibitors (73% vs. 54%; P = .04) and steroids (62% vs. 41%; P = .02), said Dr. Hoekman of the Academic Medical Center, Amsterdam.

There was no difference between the step-up and top-down groups in long-term remission rates (70% vs. 73%; P = .85).

The top-down group, however, had significantly fewer flares than the step-up group (7% vs. 19%; P = .01) and a longer time to first flare (median 9 semesters vs. 5 semesters; P = .02), he said.

There were no differences between groups in rates of hospitalization or surgery for Crohn’s disease, new fistula, or rescue treatment, defined as use of cyclosporine, experimental therapy, or surgery.

A review of the endoscopy reports suggested a trend for fewer large ulcers per patient in the top-down group than the step-up group, but this did not reach statistical significance (14% vs. 24%; P = .11), Dr. Hoekman said. The median proportion of endoscopies with remission also was similar (49% vs. 43%; P = .46).

Rates of adverse events also were similar in the top-down and step-up groups including infusion reactions (14% vs. 10%), serious infection (22% vs. 10%), malignancy (0 vs. 1 event), and dysplastic lesions (0 vs. 2 events), he said.


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