| International Session（Panel Discussion）1(JSGE・JGES・JSGS) |
| Fri. November 1st 10:00 - 12:00 Room 7: Portopia Hotel South Wing Ohwada C |
PROFILE a randomized, biomarker-stratified clinical trial of treatment strategies in newly-diagnosed Crohn's disease
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| Nurulamin Noor1,2, On behalf of PROFILE Study Group1,2 | |||
| 1University of Cambridge, 2Cambridge University Hospitals NHS Foundation Trust | |||
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| We evaluated clinical utility of a biomarker in patients receiving "top-down" or "accelerated step-up" therapy in newly-diagnosed, active Crohn's disease. PROFILE (PRedicting Outcomes For Crohn's dIsease using a moLecular biomarker, ISRCTN 11808228) was an open-label, biomarker-stratified, randomized controlled trial of adults with newly-diagnosed Crohn's disease (Harvey Bradshaw Index >7 and C-reactive protein > upper limit of normal or fecal calprotectin >200 ug/g, plus endoscopic inflammation). Patients were randomized to "top-down" (infliximab/immunomodulator) or "accelerated step-up" treatment stratified by: biomarker subgroup (IBDhi/IBDlo), endoscopic inflammation (mild/mod/severe) and extent (colonic/other). The primary endpoint was sustained steroid and surgery-free remission to week 48 and the key secondary endpoint was endoscopic remission (absence of ulcers) at week 48. 386 patients were randomized. Median time from diagnosis to enrolment was 12 days (0-191). Primary outcome data from 379 eligible participants showed sustained steroid and surgery-free remission was more frequent in "top-down" versus "accelerated step-up" (79% vs 15%, absolute difference 64%, 95% CI=57 to 72%, p<0.0001), with no biomarker-treatment interaction effect. Endoscopic remission at week 48 was greater in "top-down" versus "accelerated step-up" (67% vs 44%, absolute difference 23%, 95% CI=11 to 36%, p-value <0.0001). The biomarker did not show clinical utility. "Top-down" treatment with combination infliximab/immunomodulator achieved substantially better outcomes compared to "accelerated step-up" therapy and should be considered standard-of-care for patients with newly-diagnosed active Crohn's disease. |
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Index Term 1: Crohn's disease Index Term 2: biomarker-stratified clinical trial |
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