TOP-DOWN treatment for newly diagnosed Crohn’s disease significantly outperforms the conventional accelerated step-up approach, according to PROFILE, a multicentre, open-label, biomarker-stratified, randomised controlled trial.
The study, conducted between December 2017–January 2022, enrolled 386 adults with active Crohn’s disease confirmed by clinical symptoms, inflammatory markers, and endoscopic evidence. Patients were randomised equally to either the top-down or accelerated step-up group after blood testing for a biomarker derived from T-cell transcriptional signatures. Despite the biomarker-based stratification, allocation was blinded, and all participants were treated without knowledge of their biomarker status.
The primary endpoint, sustained steroid-free and surgery-free remission at 48 weeks, revealed a dramatic difference between treatment strategies. Among the 379 participants with available primary outcome data, 79% of those in the top-down group achieved remission compared to just 15% in the step-up group, reflecting an absolute difference of 64 percentage points (95% CI: 57–72; P<0.0001). The biomarker stratification did not significantly influence treatment outcomes (absolute difference 1 percentage point, 95% CI: –15–15; P=0.944).
Beyond superior remission rates, the top-down group experienced substantially fewer complications. Adverse events were nearly halved (168 in the top-down group versus 315 in the step-up group), and serious adverse events were also reduced (15 versus 42). The number of complications requiring abdominal surgery was notably lower in the top-down group, with just one instance compared to ten in the step-up group. Rates of serious infections were comparable (3 versus 8).
The findings challenge traditional step-up management, which begins with milder therapies and escalates as needed. By contrast, the top-down approach aggressively targets inflammation early, achieving better clinical outcomes and minimising disease-related complications.
The study concludes that the top-down strategy should become the standard of care for active Crohn’s disease, while the biomarker, although promising in concept, requires further refinement before clinical application.
Ada Enesco, EMJ
Reference
Noor NM 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. 2024;9(5):415-427.
