P0610 Comparison of endoscopic remission and MRI defined remission using the simplified MaRIA score at week 48 from the PROFILE trial
Authors: Bhandari M , Noor N , Paverd H , De Paepe K , Godfrey E , Hickman K , Khwaja S , Lee J , Raine T , Kennedy N , Upponi S , Parkes M ,   PROFILE study group
Published: January 2025

Background

In the PROFILE trial patients newly-diagnosed with Crohn’s disease on “top-down” (infliximab + immunomodulator) treatment had significantly higher rates of ulcer-free endoscopic remission (SES-CD ulcer subscore = 0) at week 48 compared to those on “accelerated step-up” therapy (67% vs 44%, p&lt;0.0001) [1]. Here, we explored the utility of MRI-defined remission as an alternative week 48 endpoint.

Methods

PROFILE enrolled 386 patients with endoscopically active new-diagnosis Crohn’s disease. MRI-enterography was performed at week 48 and centrally-read by a validated pool of 5 GI radiologists. Endoscopic and MRI defined remission was compared between “top-down” and “accelerated step-up” groups. Detection of remission and ulceration were compared pairwise between MRI and colonoscopy using McNemar’s test. MRI remission was defined by a simplified Magnetic Resonance Index of Activity (MARIAs) global score of 0 or ulcer subscore of 0; and endoscopic remission by SES-CD ulcer subscore of 0 (no ulcers - as published) and ≤1 (i.e. permitted ulcers 1-5mm). MARIAs sigmoid + descending colon scores were merged to enable comparison to SES-CD in five segments (terminal ileum, right, transverse, left colon and rectum). Data were analysed using Python 3.12.1 packages numpy, pandas, matplotlib (VS Code).

Results

Week 48 endoscopic data were available for 252 participants. Endoscopic remission using SES-CD ulcer subscore ≤1 at week 48 was more frequent in “top-down” compared to “accelerated step-up” (86% [115/134] vs 71% [84/118] patients, p=0.004). Week 48 MRI data were available for 208 of these participants. MRI remission at week 48 was similar between “top-down” and “accelerated step-up” groups by global MARIAs score (81% [89/109] vs 79% [79/99], p=0.720) and MARIAs ulcer subscore (95% [104/109] vs 96% [95/99], p=0.728). McNemar’s pairwise comparison demonstrated endoscopy had superior sensitivity for detecting ulcers compared to MRI at week 48 (p&lt;0.0001). Comparing SES-CD vs MARIAs across 1035 segments in 208 patients: 43 segments had ulcers &gt;5mm (SES-CD ulcer subscore &gt;1) on colonoscopy of which 1/43 was detected by MRI; and 96 segments had ulcers 1-5mm (SES-CD ulcer subscore = 1), with 4/96 detected by MRI. The remaining 884 segments were normal (SES-CD ulcer subscore = 0).

Conclusion

MRI had low sensitivity for detecting ulceration compared to colonoscopy. The difference in week 48 outcomes in PROFILE between “top-down” and “accelerated step-up” treatment arms using endoscopic definitions of remission were not seen on MRI. As even mild endoscopic activity correlates with adverse long-term prognosis in Crohn’s [2] so MARIAs-defined trial endpoints may have low utility compared to the endoscopic gold-standard.

References

[1]Noor NM, Lee JC, Bond S, Dowling F, Brezina B, Patel KV, Ahmad T, Banim PJ, Berrill JW, Cooney R, De La Revilla Negro J, de Silva S, Din S, Durai D, Gordon JN, Irving PM, Johnson M, Kent AJ, Kok KB, Moran GW, Mowat C, Patel P, Probert CS, Raine T, Saich R, Seward A, Sharpstone D, Smith MA, Subramanian S, Upponi SS, Wiles A, Williams HRT, van den Brink GR, Vermeire S, Jairath V, D’Haens GR, McKinney EF, Lyons PA, Lindsay JO, Kennedy NA, Smith KGC, Parkes M; PROFILE Study Group. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427. doi: 10.1016/S2468-1253(24)00034-7. Epub 2024 Feb 22. PMID: 38402895; PMCID: PMC11001594.

[2]Yzet C, Diouf M, Le Mouel JP, Brazier F, Turpin J, Loreau J, Dupas JL, Peyrin-Biroulet L, Fumery M. Complete Endoscopic Healing Associated With Better Outcomes Than Partial Endoscopic Healing in Patients With Crohn’s Disease. Clin Gastroenterol Hepatol. 2020 Sep;18(10):2256-2261. doi: 10.1016/j.cgh.2019.11.025. Epub 2019 Nov 16. PMID: 31743755.