PROFILE: Top-down treatment strategy benefits patients with early Crohn’s disease

A top-down treatment strategy resulted in improved outcomes compared with an accelerated step-down treatment strategy in patients with newly diagnosed Crohn’s disease (CD), without increasing the risk of serious infections.

“There has been debate on whether a top-down or accelerated step-up treatment strategy should be utilised for the management of patients with previously untreated CD,” said Dr Nuru Noor (Cambridge University Hospitals, UK) [1]. “Two prior prospective observational studies had validated a prognostic biomarker to identify patients at high risk of recurrent flares” [2,3]. The PROFILE trial (ISRCTN11808228) built on these observational studies and aimed to answer 2 questions [4]. First, can a prognostic biomarker guide management and improve outcomes for newly diagnosed patients with CD? Second, what is the optimal treatment strategy for these patients?

The research team used a blood-based biomarker to allocate the included participants (n=386) into a low-risk group (IBD-low) and a high-risk group (IBD-high) [1,2]. All participants started with a steroid taper for 2 weeks [1]. Subsequently, they were randomised 1:1 to a top-down strategy, in which participants started on infliximab and an immunomodulator, or an accelerated step-up strategy, in which participants started with a complete steroid wean and received an immunomodulator if a flare was observed, followed by infliximab in case of a second flare, and followed with a steroid taper if the patient had yet another flare. The primary endpoint was sustained steroid-free and surgery-free remission from the induction of steroids until week 48.

The median time from diagnosis to enrolment was 12 days. The primary endpoint was achieved by 79% of the participants in the top-down arm and by 15% of those in the step-up arm (Δ64%; 95% CI 57–72; P<0.0001). Next, Dr Noor showed that the biomarker did not demonstrate utility for stratifying to either treatment arm.

“Both adverse events and serious adverse events were lower with top-down therapy compared with accelerated step-up therapy. Looking at serious adverse events, we did not see any increase in serious infections in the top-down group (n=3) compared with the accelerated step-up group (n=8),” added Dr Noor. “Finally, we noticed that the need for urgent abdominal surgery was higher in the accelerated step-up arm than in the top-down arm” (post-hoc OR 0.095; 95% CI 0.0001–0.51).

Dr Noor highlighted that “the inclusion criteria for PROFILE were pragmatic and included patients with symptoms, raised inflammatory markers, and endoscopic evidence of disease activity. A definition which encompasses most patients presenting with a new diagnosis of active CD.”

“These results indicate that a top-down treatment strategy should be utilised in the majority of patients with newly diagnosed active CD,” concluded Dr Noor.

1. Noor N, et al. PROFILE trial: a biomarker-stratified, clinical trial of treatment strategies in patients with newly-diagnosed Crohn’s disease. OP01, 19^th Congress of ECCO, 21–24 February 2024, Stockholm, Sweden.
2. Biasci D, et al. Gut. 2019;68(8):1386-1395.
3. Lee JC, et al. J Clin Invest. 2011;121(10):4170-4179.
4. Noor N, et al. Lancet Gastroeterol Hepatol. Feb 21:S2468-1253(24)00034-7.

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Posted on 18 April 202418 April 2024