Early “Top-Down” Therapy Reduces Long-Term Complications in Crohn’s Disease
Early use of biologic-based “top-down” therapy in newly diagnosed Crohn’s disease (CD) is associated with sustained reductions in surgery, hospitalization, and disease progression over more than four years of follow-up, according to extended results from the PROFILE trial. The findings suggest that early control of inflammation may alter the long-term disease course.
PROFILE was a randomized controlled trial comparing top-down therapy—initial treatment with infliximab plus an immunomodulator—with a conventional accelerated step-up approach. Initial 48-week results showed improved short-term outcomes with top-down therapy. The current analysis evaluated long-term outcomes after patients returned to routine clinical care.
Among 357 patients with follow-up data (median ~4.5 years), those initially treated with step-up therapy had significantly worse outcomes despite eventual exposure to advanced therapies. Abdominal surgeries were more frequent in the step-up group, with an overall fivefold higher risk compared with the top-down group (odds ratio 5.00). From diagnosis, 27 surgeries occurred in step-up patients versus 6 in those initially treated with top-down therapy.
Disease progression was also more common in the step-up group, with higher rates of stricturing and penetrating complications. Hospitalizations followed a similar pattern, occurring nearly four times more often in step-up patients.
The authors reported that “top-down treatment was associated with reduced disease progression, reduced hospitalization, and reduced need for abdominal surgery.” They concluded that “early and effective control of inflammation is associated with a modified course of Crohn’s disease.”
Importantly, these differences persisted even though most patients in the step-up group eventually received advanced therapies, suggesting that timing of intervention—not just treatment exposure—affects long-term outcomes.
Reference
Nurulamin Noor, Haiyan Zheng, Mohmmed Tauseef Sharip, et al. PROFILE trial 4-year follow-up shows early effective “top-down” therapy from diagnosis modifies the course of Crohn’s disease. Presented at: Digestive Disease Week; May 2–5, 2026; Chicago, Illinois.
