Early Top-Down Anti-TNF Linked to Fewer Crohn’s Surgeries
Clinical Summary
- Early infliximab plus immunomodulator therapy was associated with fewer Crohn’s disease-related abdominal surgeries over approximately 5 years.
- Step-up treatment was associated with earlier surgery, hospitalization, and progression to B2 (stricturing) or B3 (fistulizing) complications.
- Serious infection and malignancy rates did not differ meaningfully between treatment groups.
The UK PROFILE randomized controlled trial found that initiating top-down antitumor necrosis factor (anti-TNF) therapy at diagnosis of Crohn’s disease resulted in better long-term outcomes than conventional step-up care. Follow-up data from 40 UK hospitals suggest that early infliximab plus an immunomodulator may alter the disease course by reducing surgery, hospitalization, and disease progression.
Study Findings
PROFILE enrolled patients aged 16–80 years with newly diagnosed Crohn’s disease. Investigators randomly assigned 386 eligible participants to top-down treatment with infliximab plus an immunomodulator or to a protocolized step-up strategy for 48 weeks. After that period, patients returned to local standards of care.
Post-week 48 records were available for 358 participants, representing 93% of the original trial population. Median follow-up from randomization was 1809 days, or approximately 5 years.
By the end of follow-up, 172 of 193 patients assigned to step-up therapy and 191 of 193 assigned to top-down treatment had received a biologic or immunomodulator.
The primary outcome analysis recorded 28 Crohn’s disease-related abdominal surgeries among 26 patients originally assigned to step-up care, compared with 6 surgeries among 6 patients assigned to top-down treatment. Time to surgery was shorter with step-up treatment (adjusted hazard ratio [aHR], 5.23; 95% CI, 1.99–13.76; P=.0008).
Crohn’s-related hospitalizations occurred in 41 step-up patients versus 22 top-down patients. Time to first hospitalization was shorter in the step-up group (aHR, 2.01; 95% CI, 1.18–3.41; P=.017).
Progression to stricturing or fistulizing complications affected 32 of 192 step-up patients and 13 of 193 top-down patients. Step-up care was associated with shorter time to progression (aHR, 2.46; 95% CI, 1.25–4.86; P=.010).
Clinical Implications
The findings extend PROFILE’s previously reported 48-week results and suggest that treatment decisions made at Crohn’s disease diagnosis may have effects lasting several years. Early control with combination anti-TNF therapy was associated with fewer major disease-related events, even though nearly all patients in both groups eventually received a biologic or immunomodulator.
This difference may be clinically important because abdominal surgery, hospitalization, and stricturing or fistulizing complications reflect substantial disease burden. The results support further consideration of early top-down therapy for newly diagnosed Crohn’s disease rather than reserving advanced treatment until conventional step-up care fails.
Safety outcomes were similar between groups. Serious infections occurred in 12 step-up patients and 14 top-down patients; malignancies occurred in 5 and 3 patients, respectively. The source reported no between-group difference for either safety outcome.
The 5-year PROFILE follow-up indicates that starting infliximab plus an immunomodulator at diagnosis may reduce surgery, hospitalization, and disease progression without an observed safety disadvantage. Further evidence will be needed to confirm the proposed disease-modifying effect.
Reference
Barberio B, D'Amico F, Laterza L. Real-world effectiveness and safety of upadacitinib in patients with Crohn's disease—a multicentre prospective study from the Italian group for the study of inflammatory bowel diseases (IG-IBD). Aliment Pharmacol Ther. Published online September 10, 2026. https://doi.org/10.1111/apt.70970
