Top-down vs. accelerated step-up for new CD

September 16, 2024

Issue 18

Clinical Question

Should biologics be used early in all new Crohn’s disease (CD) patients?

Editor’s Bottom Line

Although its biomarker results were disappointing, this study adds important evidence that early and effective treatment of Crohn’s disease can improve outcomes and limit progression.

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. 2024;9(5):415–27. https://www.thelancet.com

Synopsis

Between 2017 and 2022, researchers at multiple centers in the United Kingdom enrolled 386 adults with newly diagnosed active CD, defined as a Harvey-Bradshaw Index ≥7 along with either elevated C-reactive protein or fecal calprotectin, or both, and endoscopically-proven inflammation.

As part of the open-label trial, participants were randomly assigned in a 1:1 ratio to receive either “top-down” therapy (infliximab with an immunomodulator) or “accelerated step-up” treatment (corticosteroids, weaned and followed by treatment escalations in case of relapses).

Participants were also tested for a blood-based T-cell-derived biomarker signature using the PredictSURE-IBD assay. This tool has previously been shown to predict likelihood of treatment escalation.

Patients were a mean 33.6 years of age at the time of enrolment and 46% were female. The median time from diagnosis to trial enrolment was 12 days. Disease in most patients was not limited to the colon, and 92% had moderate-to-severe endoscopic inflammation. Patient characteristics were similar in the two groups.

Data showed that 79% of those in the top-down group achieved steroid-free and surgery-free remission at 48 weeks after treatment outset, compared to 15% in the accelerated step-up group (p<0.0001). The biomarker assay failed to predict treatment outcomes in either group.

Secondary outcomes such as quality of life, number of relapses, steroid courses and hospitalizations were all significantly better when infliximab was used early, and only one patient in the top-down group required abdominal surgery during the 48-week period, compared to 10 patients in the step-up group.

Early use of infliximab and an immunomodulator proved safer, with 168 adverse events (most commonly disease relapses) and 15 serious adverse events in the top-down group, compared to 315 adverse events and 42 serious adverse events in the accelerated step-up group. There were no differences in rates of infection between groups.

The time from treatment outset to disease flare was longer in the top-down group. There were no differences in time-to-flare based on biomarker levels.

Details

Study Design: Prospective, open-label, controlled
Funding: Wellcome and PredictImmune Ltd.
Allocation: Randomized
Setting: Multicenter
Level of Evidence: 1b