PROFILE Trial: 5-Year Data Show Improvements With Top-Down Therapy Strategy | Gastro Today

According to a recent follow-up study with participants from the PROFILE trial, early top-down anti–tumor necrosis factor (TNF) therapy after diagnosis correlated with superior long-term outcomes compared with step-up treatment for patients with Crohn’s disease.

Five-Year PROFILE Data Favor Top-Down Strategy in Crohn’s Disease

A team of researchers from the UK conducted the study and published their findings in The Lancet Gastroenterology & Hepatology.

The researchers highlighted that superior 48-week outcomes in Crohn’s disease with top-down anti-TNF treatment after diagnosis compared with “a conventional step-up strategy” were previously observed in the PROFILE trial.

A follow-up study was conducted with participants of the PROFILE trial to determine whether the benefits from top-down treatment after diagnosis would result in “modification of the long-term disease course.”

The follow-up study outlined the parameters of the PROFILE trial, which was a multicenter, open-label, randomized controlled trial in the UK and was conducted across 40 hospitals. Eligible patients included individuals between the ages of 16 and 80 years who had been recently diagnosed with Crohn’s disease.

According to PROFILE’s methodology, eligible participants were randomized to receive either top-down therapy with infliximab plus an immunomodulator or step-up therapy for 48 weeks. After 48 weeks, patients in both cohorts returned to the local standard-of-care treatment for Crohn’s disease.

The study authors explained that after 48 weeks, objective outcome data were collected for 5 years, and the primary outcome was the need for abdominal surgery related to the disease. For the follow-up study, the investigators analyzed PROFILE data based on the original randomization and intention-to-treat population. In addition, they used the Kaplan-Meier method and the Cox proportional hazards model to conduct time-to-event analyses.

A total of 483 patients were evaluated for the PROFILE trial from December 29, 2017, to January 5, 2022, and 386 patients were selected and randomly assigned to top-down therapy (n=193) or step-up therapy (n=193).

According to the results, 93% of patients from the trial had records after week 48 that investigators were able to review. Of those patients, 51% received top-down therapy (n=182) and 49% received step-up therapy (n=176).

At the median follow-up point of approximately 5 years after randomization (1,809 days), 89% of the patients in the step-up cohort (n=172) and 99% of patients in the top-down cohort (n=191) received biologic or immunomodulator therapy.

In the step-up cohort, 26 patients underwent 28 disease-related abdominal operations compared with the top-down cohort, in which six patients underwent six disease-related abdominal operations. However, time to surgery was found to be shorter in the step-up cohort (adjusted hazard ratio, 5.23; 95% CI, 1.99-13.76; P=0·0008).

Additional findings revealed that disease-related hospital admissions were more common in the step-up cohort (n=41) versus the top-down cohort (n=22). Time to first admission was shorter in the step-up group, and incidence of B2 or B3 complications occurred more frequently in the step-up group (n=32) versus the top-down group (n=13). The investigators also reported time to disease progression findings, which were shorter in the step-up cohort.

In terms of safety outcomes, no difference in serious infections or malignancies was observed in either group.

Overall, the investigators concluded that top-down anti-TNF treatment administered early after diagnosis correlated with improved 5-year long-term outcomes compared with step-up therapy and “is suggestive of a disease-modifying effect in Crohn’s disease.”