Five-year follow-up from the PROFILE randomized trial found that starting anti-TNF therapy immediately after diagnosis was associated with substantially better long-term outcomes than a conventional step-up approach in adults with newly diagnosed, moderate-to-severe Crohn’s disease. Among 386 randomized patients, those assigned to top-down treatment with infliximab plus an immunomodulator had fewer Crohn’s-related abdominal surgeries: 6 patients (3%) vs. 26 (13%) in the step-up group. The adjusted hazard ratio for surgery was 5.23, favoring top-down treatment.
Top-down treatment was also associated with lower rates of disease progression to stricturing or penetrating complications (7% vs. 17%) and Crohn’s-related hospitalization (11% vs. 21%). The absolute risk reduction for surgery was 10%, corresponding to an estimated number needed to treat of 9 over more than five years.
Importantly, serious infections and malignancies were similar between groups, although the study was not powered to establish long-term safety differences.