Dr Nuralamin Noor
A top-down approach to treating patients newly diagnosed with Crohn’s disease is superior to an accelerated step-up approach, according to results presented at ECCO 24 Congress.
Dr Nurulamin Noor, from the Department of Gastroenterology at Cambridge University Hospitals NHS Foundation Trust in the UK, presented results from the PROFILE study, the first biomarker-stratified comparison of the two treatment strategies.
The trial results were simultaneously published in The Lancet Gastroenterology & Hepatology [link here].
The study’s 389 newly diagnosed patients from 40 UK hospitals all received two-weeks steroid induction for active Crohn’s disease before randomisation to either infliximab plus immunomodulator and steroid taper (top-down) or steroid taper alone (accelerated step-up) for 4 weeks.
At reviews at 4, 16, 32 and 48 weeks after randomisation, patients in the top-down approach and who were not in remission received an additional course of steroids.
Those in the accelerated step-up approach who were not in remission were started on steroids and an immunomodulator for a first flare and infliximab plus an immunomodulator for a subsequent flare.
Dr Noor told the meeting that the primary endpoint of sustained steroid-free and surgery-free remission through to week 48 was achieved by 79% of patients in the top-down approach compared to 15% in the step-up approach (p<0.0001).
In a key secondary outcome, high levels of endoscopic remission at week 48 were seen with both top-down and step-up approaches while top-down remained superior (67% v 44%; p<0.0001).
All other secondary outcomes including quality of life, number of flares and steroid courses were significantly improved in the top-down versus the accelerated step-up approaches.
Dr Noor said the use of a 17-gene blood-based prognostic biomarker to categorise patients into groups at either high or low risk for future escalation of treatment made no difference to the clinical outcomes. Patients in the high-risk group had similar rates of remission (80% v 17%; p <0.0001) as people in the low-risk group (77% v 14%; p<0,0001) and the overall cohort.
The study reported ten patients in the step-up approach required urgent abdominal surgery for penetrating or stricturing complications of their disease compared to only one patient in the top-down approach who required urgent abdominal surgery for a gallstone ileus.
“There were fewer adverse events or serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42),” the investigators wrote in the journal.
“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.”
They concluded that “the case appears clearcut for implementation of top-down treatment as the standard of care for most patients as soon as possible after diagnosis.”
Out now – results from the @PROFILECrohn trial, a biomarker-stratified comparison of top-down vs accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s diseasehttps://t.co/B0j5pVqZno #GITwitter #IBD #ECCO24 #ECCO2024 pic.twitter.com/KGV6egYgRz
— The Lancet Gastroenterology & Hepatology (@LancetGastroHep) February 22, 2024