EARLY top-down anti-TNF treatment from Crohn’s disease diagnosis was associated with improved 5-year outcomes compared with step-up therapy, according to follow-up results from participants in PROFILE, a multicentre, open-label, randomised controlled trial. These findings highlighted how early top-down intervention might have a disease-modifying effect in Crohn’s disease.
PROFILE included 386 patients aged 16–80 years with newly diagnosed Crohn’s disease and was completed in 40 hospitals in the UK. Patients were randomly assigned either a top-down treatment strategy involving infliximab and an immunomodulator or a step-up strategy.
Previous results from the PROFILE trial revealed better 48-week outcomes for patients with Crohn’s disease who received top-down anti-TNF treatment from diagnosis compared with patients who received conventional step-up therapy.
In this study, researchers followed up with participants of the PROFILE trial using outcome data extracted for up to 5 years after the week 48 visit to assess whether the benefits of a top-down treatment strategy resulted in long-term disease course modification. The primary outcome was the need for Crohn’s disease-related abdominal surgery.
In total, 358 patients had post-week 48 records and median follow-up was approximately 5 years. Notably, 89% of patients receiving step-up treatment and 99% of patients receiving top-down treatment had received biological or immunomodulator therapy.
Twenty-eight Crohn’s disease-related abdominal surgeries were recorded in 26 patients who received conventional step-up treatment, compared with six surgeries in six patients who received early top-down therapy.
Patients in the step-up group had a shorter time to surgery than patients in the top-down group (adjusted hazard ratio [aHR] 5.23; 95% CI 1.99–13.76; p=0.0008).
Patients who received conventional step-up treatment were also more likely to experience a Crohn’s disease-related hospital admission than those who received early top-down treatment (21% vs 11%). Time to first hospital admission was significantly shorter in the step-up group (aHR 2.01; 95% CI 1.18–3.41; p=0.017).
Progression to stricturing or penetrating Crohn’s disease was also less frequent in patients who received early top-down treatment (7% vs 17%), and time to disease progression was longer in this group (aHR 2.46; 95% CI 1.25–4.86; p=0.010).
Overall, researchers concluded that early top-down anti-TNF treatment from diagnosis was associated with improved long-term outcomes at 5 years compared with step-up treatment. The authors continued to explain that the robustness of these findings was supported by the completeness of long-term data and benefits across all major disease modification outcomes.
These results suggest that early top-down treatment may have a disease-modifying effect in Crohn’s disease.
Reference
Noor NM et al. Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn’s disease: 5-year follow-up of the PROFILE trial. Lancet Gastroenterol Hepatol. 2026; DOI: 10.1016/S2468-1253(26)00192-5.
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