Early top-down anti-TNF treatment for newly diagnosed Crohn’s disease significantly reduces the need for abdominal surgery and long-term hospital admissions compared with conventional step-up therapy, according to 5-year follow-up results from the PROFILE trial published in The Lancet Gastroenterology & Hepatology by N.M. Noor and colleagues. The multicentre, open-label, randomised controlled trial tracked 386 patients across 40 hospitals in the UK, revealing that early intervention alters the long-term disease course.
PROFILE Trial 5-Year Design and Patient Cohort
The PROFILE trial enrolled patients aged 16 to 80 years with newly diagnosed Crohn’s disease. Researchers randomly assigned participants to either a top-down treatment strategy—utilizing infliximab alongside an immunomodulator—or a conventional step-up strategy. Previous 48-week findings already favored the top-down approach, prompting investigators to extend observation.
To evaluate whether initial benefits translated into lasting disease modification, researchers extracted outcome data for up to 5 years following the week 48 visit. Out of the original cohort, 358 patients maintained post-week 48 records, yielding a median follow-up of approximately 5 years. During this period, 99% of the top-down group and 89% of the step-up group received biological or immunomodulator therapy.
Did you know? The PROFILE trial was conducted across 40 different hospitals in the UK.
Surgical Rates and Hospital Admissions Compared
Long-term data showed a stark difference in surgical interventions between the two treatment arms. Investigators recorded 28 Crohn’s disease-related abdominal surgeries among 26 patients in the conventional step-up group. In contrast, only six surgeries occurred in six patients who received early top-down therapy.
Patients managed with step-up therapy faced a significantly shorter time to surgery, with an adjusted hazard ratio (aHR) of 5.23 (95% CI 1.99–13.76; p=0.0008). Hospital admissions followed a similar pattern. While 21% of the step-up cohort experienced a Crohn’s-related hospital admission, only 11% of the top-down group did. Time to first hospital admission was also significantly shorter in the step-up group (aHR 2.01; 95% CI 1.18–3.41; p=0.017).
Disease Progression and Stricturing Outcomes
Beyond surgeries and hospitalizations, the trial tracked structural bowel damage. Progression to stricturing or penetrating Crohn’s disease occurred in 17% of patients receiving conventional step-up treatment. That figure dropped to 7% among patients assigned to early top-down treatment.
Time to disease progression was markedly longer in the top-down arm, showing an adjusted hazard ratio of 2.46 (95% CI 1.25–4.86; p=0.010). According to the study authors, the robustness of these findings is reinforced by complete long-term data and consistent benefits across all major metrics of disease modification.
Pro Tip: Clinicians reviewing inflammatory bowel disease management protocols can examine the full study details in The Lancet Gastroenterology & Hepatology (DOI: 10.1016/S2468-1253(26)00192-5) to assess patient selection criteria for early biologic therapy.
Frequently Asked Questions
What was the primary outcome measured in the PROFILE trial 5-year follow-up?
The primary outcome was the need for Crohn’s disease-related abdominal surgery.
How many patients participated in the PROFILE trial?
The trial included 386 patients newly diagnosed with Crohn’s disease across 40 hospitals in the UK, with 358 patients included in the 5-year post-week 48 analysis.
Did early top-down therapy reduce hospital admissions?
Yes. Patients receiving step-up treatment experienced higher rates of hospital admissions (21%) compared to those receiving early top-down treatment (11%).
What medications were used in the top-down strategy?
The top-down treatment strategy involved infliximab combined with an immunomodulator.
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