Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn’s Disease Treated with Anti-Tumour Necrosis Factor Therapy

Abstract

Background Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn’s disease [CD]. Aims We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. Methods All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn’s Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. Results Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7–34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3–13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > −30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0–0.9]; p = 0.037). Conclusion Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing in Crohn’s disease

“…CD‐related bowel surgery is an objective endpoint but was relatively rare in patients with endoscopic mucosal healing, MRI healing and transmural healing in our cohort. However, we confirmed the data showing that endoscopic mucosal healing, 9 MRI healing 11,15 and transmural healing 14 were associated with decreased risk of surgery compared to no healing in patients with CD. We investigated the potential of transmural healing or MRI healing to prevent bowel damage progression with a more sensitive composite endpoint including surgery, occurrence of a new stricture or fistula or worsening of pre‐existing stricture or fistula 11 .…”

“…However, we confirmed the data showing that endoscopic mucosal healing, 9 MRI healing 11,15 and transmural healing 14 were associated with decreased risk of surgery compared to no healing in patients with CD. We investigated the potential of transmural healing or MRI healing to prevent bowel damage progression with a more sensitive composite endpoint including surgery, occurrence of a new stricture or fistula or worsening of pre‐existing stricture or fistula 11 . Our data were consistent with those reported from a multicenter prospective study suggesting that an early MRI improvement after anti‐TNF induction was associated with a lower risk of bowel damage progression 11 .…”

“…Surgery meant CD‐related subsequent intestinal resection excluding drainage of perianal lesions. Bowel damage progression was considered in case of bowel resection, new stricture or fistula, or worsening of pre‐existing stricture (increase in pre‐stenotic dilation on imaging or occurrence of major obstructive symptoms) or fistula (new abscess or new fistula tract) 11 . Hospitalisation was defined as any admission related to CD symptomatic flare.…”

“…However, their data did not provide enough evidence to draw firm conclusions on the superiority of transmural healing over mucosal healing as a therapeutic target. Firstly, the interval between MRI and endoscopy (up to 6 months in their work) may have resulted in the resolution of active disease (noted on MRI) by the time of colonoscopy 11 . Secondly, the short follow‐up (12 months) did not give any information on the long‐term outcomes especially the progression of bowel damage.…”

“…In this context, magnetic resonance imaging (MRI) could be a relevant alternative as it is felt by the patients as a less burdensome procedure than endoscopy 10 . MRI is able to perform a concomitant evaluation of the colon and the small bowel, and demonstrated its reliability to assess transmural inflammation, 11,12 to detect extramural complications as well as to monitor therapeutic efficacy 11,13 . Then, transmural healing is a very promising endpoint as it has been associated with sustained clinical remission, 11,14,15 reduced risk of therapeutic escalation, 14 decreased risk of surgery 14,15 and prevention of bowel damage progression 11 .…”