Five-year data from the PROFILE trial, published in The Lancet Gastroenterology & Hepatology, reveal a significant long-term benefit for patients with Crohn’s disease who receive early, aggressive “top-down” therapy with infliximab plus an immunomodulator compared to a conventional step-up approach. The study, a multicenter, open-label, randomized controlled trial conducted across 40 hospitals in the UK, included 386 patients recently diagnosed with Crohn’s disease.
PROFILE Trial Design and Methodology
The PROFILE trial randomized participants to receive either top-down therapy or step-up therapy for 48 weeks. After this initial period, all patients returned to their local standard-of-care treatment. Researchers collected objective outcome data for 5 years, with the primary outcome being the need for abdominal surgery related to the disease. The analysis was based on the original randomization and intention-to-treat population, using the Kaplan-Meier method and the Cox proportional hazards model for time-to-event analyses.
Long-Term Outcomes Favor Top-Down Therapy
At a median follow-up of approximately 5 years (1,809 days), results showed stark differences between the cohorts. In the step-up cohort, 26 patients underwent 28 disease-related abdominal operations, compared to just six patients in the top-down cohort. Time to surgery was significantly shorter for the step-up group, with an adjusted hazard ratio of 5.23 (95% CI, 1.99-13.76; P=0·0008). Disease-related hospital admissions were also more common in the step-up cohort (n=41) versus the top-down cohort (n=22), with time to first admission and incidence of B2 or B3 complications occurring more frequently in the step-up group.
Treatment Shows Long-Term Benefits
Regarding safety, no difference in serious infections or malignancies was observed between the two groups. The study authors concluded that top-down anti-TNF treatment administered early after diagnosis is suggestive of a disease-modifying effect in Crohn’s disease
, as it correlated with improved 5-year long-term outcomes compared to step-up therapy.
