Biomarker Study Finds ‘Clearcut’ Case for Early Advanced Therapy for CD

A study designed to gauge the ability of a blood-based biomarker to guide therapy for patients with newly diagnosed Crohn’s disease (CD) instead found that top-down treatment beginning at diagnosis is highly effective and safe, regardless of biomarker status. Researchers published their findings online ahead of print in The Lancet Gastroenterology & Hepatology.

“These findings are potentially transformative for the management of Crohn’s disease,” wrote corresponding author Miles Parkes, FMedSci, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, and study coauthors. “…While PROFILE did not identify a clinically useful biomarker, it has provided clear evidence with regards to the optimal treatment strategy from diagnosis. Indeed, the scale of the benefit with top-down management quantified in PROFILE would, if sustained, substantially weaken the case-of-need for a prognostic biomarker.”

The open-label PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) trial included 379 adults with newly diagnosed CD. Participants were randomized to either top-down (infliximab plus immunomodulator) or accelerated step-up (conventional) treatment, stratified by a blood-based biomarker observationally associated with the need for future treatment escalation. In all, 189 patients were randomized to top-down treatment and 190 to accelerated step-up treatment a median 12 days after CD diagnosis.

Study results showed no biomarker–treatment interaction effect. However, at week 48 some 79% of patients in the top-down group showed sustained steroid-free and surgery-free remission compared with 15% in the accelerated step-up group.

Adverse events, including disease flares, totaled 168 in the top-down group compared with 315 in the accelerated step-up group, according to the study. There were 15 serious adverse events in the top-down group compared with 42 in the accelerated step-up group. Meanwhile, the number of complications requiring abdominal surgery was just 1 in the top-down treatment group compared with 10 in the accelerated step-up group. There was no difference in the rate of serious infections, which was 2% in both groups.

“PROFILE provides definitive evidence for the benefit of top-down over accelerated step-up treatment, at least for patients meeting the trial inclusion criteria of active symptoms, raised CRP [C-reactive protein] or calprotectin of 200 μg/g or more, plus active inflammation on ileo-colonoscopy,” researchers wrote. “Given that this definition encompasses the majority of patients newly presenting with Crohn's disease, the case appears clearcut for implementation of top-down treatment as the standard of care for most patients as soon as possible after diagnosis.”

Reference:
Noor NM, Lee JC, Bond S, et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. Published online February 21, 2024. doi: 10.1016/S2468-1253(24)00034-7