‘Case appears clearcut’: Top-down therapy should be ‘standard of care’ for new Crohn’s
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Key takeaways:
- Researchers reported a 64-percentage point difference in sustained remission with top-down vs. accelerated step-up treatment.
- Top-down treatment also was safer, with fewer adverse events.
Early treatment with infliximab plus an immunomodulator resulted in more frequent steroid-free and surgery-free remission at 1 year compared with conventional therapy among patients with newly diagnosed Crohn’s disease, researchers reported.
“The ability to predict which patients would benefit from early advanced therapies would enable targeting of these treatments to patients who truly need them while minimizing their use in others,” Nurulamin M. Noor, PhD, of the department of gastroenterology at Cambridge University Hospitals, and colleagues wrote in The Lancet Gastroenterology & Hepatology. “Several biomarkers have been proposed in Crohn’s disease. These include a 17-gene blood-based prognostic biomarker previously shown to categorize patients into two approximately equal groups termed IBDhi and IBDlo.”
They continued: “To date neither this nor any other biomarker has been formally tested in IBD.”
In the open-label, randomized controlled PROFILE trial, Noor and colleagues evaluated the use of the 17-gene blood-based biomarker to guide therapy among 379 adults (mean age, 33.6 years; 54% men) newly diagnosed with active CD between December 2017 and January 2022. Patients were randomized to IV infliximab plus an immunomodulator (top-down therapy; n = 189) or accelerated step-up therapy (n = 190), stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation and disease location.
The primary studied endpoint was sustained steroid-free and surgery-free remission to week 48.
Noor and colleagues noted all patients in the top-down group received at least one dose of anti-tumor necrosis factor, and 93% received this as combination therapy with an immunomodulator.
Results demonstrated more frequent sustained steroid-free and surgery-free remission in the top-down group (79%) vs. the accelerated step-up group (15%), with an absolute difference of 64 percentage points (95% CI, 57-72). Researchers observed “no significant” biomarker-treatment interaction effect (absolute difference = 1 percentage point; 95% CI, –15 to 15).
Further, there were fewer adverse events in the top-down group compared with the step-up group (168 vs. 315), as well as fewer serious adverse events (15 vs. 42), including complications requiring abdominal surgery (one vs. 10) and serious infections (three vs. eight).
“PROFILE provides definitive evidence for the benefit of top-down over accelerated step-up treatment, at least for patients meeting the trial inclusion criteria of active symptoms, raised C-reactive protein or calprotectin of 200 µg/g or more, plus active inflammation on ileo-colonoscopy,” Noor and colleagues wrote. “Given that this definition encompasses the majority of patients newly presenting with Crohn’s disease, the case appears clearcut for implementation of top-down treatment as the standard of care for most patients as soon as possible after diagnosis.”
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