Early Top-Down Anti-TNF Therapy Improves 5-Year Outcomes in Crohn’s Disease

Researchers in the United Kingdom report that newly diagnosed Crohn’s disease patients who received top-down anti-TNF therapy immediately after diagnosis needed far fewer disease-related abdominal surgeries over five years than patients managed with a conventional step-up approach, according to a follow-up analysis of the PROFILE trial published in The Lancet Gastroenterology & Hepatology, DocWireNews reported.

What the PROFILE trial tested

The PROFILE trial was a multicenter, open-label, randomized controlled trial conducted across 40 UK hospitals. It enrolled 386 patients aged 16 to 80 who had recently been diagnosed with Crohn’s disease between December 29, 2017, and January 5, 2022, and randomly assigned 193 to top-down therapy with infliximab plus an immunomodulator and 193 to step-up therapy for 48 weeks. After 48 weeks, patients in both groups returned to local standard-of-care treatment, and researchers collected objective outcome data for five years. The primary outcome was the need for abdominal surgery related to the disease.

Top-down therapy cut surgeries from 28 to six

At a median follow-up of about five years (1,809 days), 26 patients in the step-up group underwent 28 disease-related abdominal operations, compared with six patients who underwent six operations in the top-down group. Time to surgery was significantly shorter in the step-up group, with an adjusted hazard ratio of 5.23 (95% CI, 1.99–13.76; P = 0.0008).

Disease-related hospital admissions were also more common in the step-up group, affecting 41 patients versus 22 in the top-down group, and time to first admission was shorter. Severe disease complications classified as B2 or B3 occurred in 32 step-up patients versus 13 in the top-down group, and time to disease progression was shorter in the step-up group as well.

No safety penalty from early biologic treatment

The investigators found no difference between the two groups in serious infections or malignancies, a finding that addresses a common concern about starting biologic therapy early in the disease course.

Researchers point to a disease-modifying effect

According to the study authors, initiating top-down anti-TNF therapy early after diagnosis was associated with better five-year long-term outcomes than step-up therapy, suggesting a disease-modifying effect in Crohn’s disease. Roughly 99% of patients in the top-down cohort and 89% in the step-up cohort received biologic or immunomodulator therapy at the median follow-up point of approximately 5 years after randomization.

Questions readers ask about early Crohn’s treatment

• What is top-down therapy in Crohn’s disease? It means starting a biologic drug — in this trial, infliximab — plus an immunomodulator immediately after diagnosis, rather than escalating treatment only after milder therapies fail, which is the step-up approach.
• How many patients were studied? The follow-up analysis reviewed records for 93% of patients from the trial. Among them, 51% were treated with top-down therapy (n=182) and 49% with step-up therapy (n=176).
• Did early biologic treatment cause more infections? No. The investigators observed no difference in serious infections or malignancies between the top-down and step-up groups.

The trial’s safety findings — no added risk of serious infection or cancer from starting anti-TNF therapy early — stand as the study’s reassuring counterweight to its surgical results.

More on this story: Study: Blood tests detect early immune shifts before IBD diagnosis