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.

In 30 seconds

This multicentre, open-label randomised trial follow-up compared early top-down infliximab plus an immunomodulator with protocolised step-up treatment in adults aged 16–80 years newly diagnosed with Crohn’s disease. Among 386 participants followed for a median of approximately 5 years, the top-down group had fewer Crohn’s-related abdominal surgeries: 6 surgeries in 6 patients versus 28 surgeries in 26 patients with step-up treatment. Hospital admissions and progression to B2 or B3 complications were also less frequent after top-down treatment. The findings suggest that early treatment may improve long-term disease outcomes.

Key findings

• Crohn’s-related abdominal surgery occurred in 6 top-down patients versus 26 step-up patients; time to surgery was shorter with step-up treatment (aHR 5·23 [95% CI 1·99-13·76]; p=0·0008).
• Crohn’s-related hospital admissions affected 22 (11%) top-down patients versus 41 (21%) step-up patients.
• Progression to B2 or B3 complications occurred in 13 (7%) top-down patients versus 32 (17%) step-up patients.
• Serious infections and malignancies did not differ between groups.

Why it matters

The follow-up suggests that treatment strategy soon after Crohn’s diagnosis may be associated with differences in outcomes years later, including surgery, hospitalisation, and disease complications. These outcomes are clinically consequential and extend the assessment beyond short-term disease control. The absence of a detected safety difference is also relevant when weighing the reported long-term benefits, while not establishing that risks are equivalent.

What to keep in mind

After the randomised 48-week treatment period, participants returned to local standards of care, so subsequent treatment was not controlled by the trial. Long-term follow-up data were available for 93% of participants.