A top-down treatment strategy resulted in improved outcomes compared with an accelerated step-down treatment strategy in newly diagnosed patients with Crohn’s disease (CD) without increasing the risk of serious infections.
The PROFILE trial aimed to answer two questions. First, can a prognostic biomarker guide management and improve outcomes for newly diagnosed patients with CD? And 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). All participants started with a steroid taper for 2 weeks. Hereafter, the study team randomized patients 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, received an immunomodulator if researchers observed a flare, followed by infliximab in case of a second flare. Patients who experienced a third flare received a steroid taper. The primary endpoint was sustained steroid-free and surgeryfree remission from the induction of steroids until week 48. Nuru Noor, MD, PhD (University of Cambridge), presented the primary findings.
The primary endpoint was achieved by 79% of the patients in the top-down arm and by 15% of the patients in the step-up arm (Δ64%; 95% CI 57–72; P<0.001). Next, Dr. Noor showed that the biomarker did not demonstrate a stratifying effect between the treatment arms: In the IBD-high group, 80% and 17% achieved the primary endpoint in the top-down and stepup arms, respectively; in the IBD-low group, the corresponding rates were 77% and 14%. With delta scores of 63% for both groups, the biomarker had no effect on treatment outcomes (95% CI -15% to 15%). “Looking at serious adverse events, we did not see an increase in serious infections in the topdown group (n=3) compared with the stepup group (n=8),” added Dr Noor. “Finally, we noticed that the need for urgent abdominal surgery was higher in the step-up arm than in the top-down arm (post hoc OR, 0.095; 95% CI, 0.0001–0.51).” “These results indicate that a top-down treatment strategy should be utilized in patients with newly diagnosed active CD,” concluded Dr. Noor. Medical writing support was provided by Robert van den Heuvel.
