Transmural Healing and MRI Remission

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practice. Our experience with 34 subjects represents the second largest study using the technology.2Subjects were participants

with previously confirmed Crohn’s disease without previous radiological or clinical features of obstruction who underwent both procedures in a 24-hour period (Fig. 1). The mucosal activity was assessed using the Simple Endoscopic Activity Score in Crohn’s Disease (SES-CD) and correlated using Spearman’s coefficient.

We found moderate correlation in SES-CD overall (0.598, P¼ 0.004), much better in proximal than distal segments (0.818 [P, 0.001], 0.522 [P ¼ 0.003], 0.480 [P¼ 0.010], 0.322 [P ¼ 0.109], and 0.166 [P¼ 0.617] in terminal ileum, right colon, transverse colon, left colon, and rectum, respectively). Unlike previous studies, we also aimed to determine the potential role of colon capsule endoscopy (CCE) in clinical decision-making. Im-pressively, agreement between colon CCE-informed recommendation for clini-cal management and actual treatment deci-sion (upgrade, downgrade/no change) was 91.2%.

The major limitation was a low rate of completion of 61.8% within the life of the battery. This was likely related to our use of a polyethylene glycol-based bowel preparation and booster, rather than of sodium phosphate as described in other studies,3 but which is avoided in Australia

because of concerns about phosphate nephrotoxicity. There were no cases of cap-sule retention requiring emergent retrieval, although one capsule was visualized during same day colonoscopy to be above a stricture and opportunistically retrieved by Roth bas-ket. This highlights the ongoing challenge of selecting participants unlikely to retain capsules because of stricturing disease.4

Overall, our data suggest that CCE is promising as an alternative for the assessment of endoscopic disease sever-ity; however, the methodology still needs further optimization.

Douglas Tjandra, MD*,†

Hajar Hasan Kheslat, MD*,†

Francesco Amico, MBBS* Finlay Macrae, MD*,†

*Department of Colorectal Medicine and Genetics The Royal Melbourne Hospital Parkville Victoria, Australia

Melbourne Medical School

The University of Melbourne Parkville Victoria, Australia

REFERENCES

1. de Chambrun GP, Peyrin-Biroulet L, Lemann M, et al. Clinical implications of mucosal healing for the man-agement of IBD. Nat Rev Gastroenterol Hepatol. 2010;7:15–29.

2. D’Haens G, Löwenberg M, Samaan MA, et al.

Orig-inal article: safety and feasibility of using the second-generation Pillcam colon capsule to assess active colonic Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13:1480–1486.e3.

3. Spada C, Riccioni ME, Hassan C, et al. PillCam colon capsule endoscopy: a prospective, randomized trial comparing two regimens of preparation. J Clin Gas-troenterol. 2011;45:119–124.

4. Postgate AJ, Burling D, Gupta A, et al. Safety, reli-ability and limitations of the given patency capsule in patients at risk of capsule retention: a 3-year technical review. Dig Dis Sci. 2008;53:2732–2738.

Transmural Healing and

MRI Remission: New

Promising Therapeutic

Targets in Crohn

’s Disease

To the Editor:

We read with great interest the article by Fernandes et al published in a recent issue of Inflammatory Bowel Dis-eases. Although magnetic resonance imaging (MRI) is a reliable tool to moni-tor patients with Crohn’s disease (CD), it is unclear that the current study provides enough evidence to drawfirm conclusions on the superiority of transmural healing over mucosal healing as a treatment target. The interval between MRI and endoscopy (up to 6 months) may have resulted in the resolution of active disease (noted on MRI) by the time of colonoscopy. Previ-ous studies have demonstrated that some medications may improve CD lesions on MRI in as early as a few weeks.1It could

partly explain the poor correlation observed in this study between MRI and endoscopy in assessing inflammatory activity, which contradicts previous works reporting a high correlation between these 2 examinations.1 Fernandes et al

sug-gested that transmural healing may have a better prognosis than mucosal healing for patients with small bowel CD. How-ever, when one examines the patients with mucosal healing but no transmural heal-ing, the major factor impacting the risk of surgery or hospitalization was the

FIGURE 1. Comparison of same ulcer (arrow) visualized by colon capsule endoscopy (left) and optical colonoscopy (right).

The authors have no conflict of interest to disclose. Copyright © 2017 Crohn’s & Colitis Foundation DOI 10.1097/MIB.0000000000001219 Published online 3 August 2017.

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Copyright © 2017 Crohn’s & Colitis Foundation. Unauthorized reproduction of this article is prohibited.

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presence of CD morphologic complica-tions (strictures and fistulas/abscesses). What is unclear is whether there was a dif-ference in disease duration between the transmural healing versus mucosal healing groups and its impact on the likelihood of transmural healing or CD-related compli-cations (strictures/fistulas). It is also unclear given the retrospective design, whether transmural healing was a real pre-dictor of subsequent therapeutic escalation or an indicator of change in physician decision making based on MRI data.

However, transmural healing is a very promising end point to monitor therapeutic response. Deepak et al reported that radio-logical response (using MRI or CT scan) was highly predictive of reductions in long-term risk of hospitalization, surgery, or steroids usage among patients with small bowel CD.2We recently showed that MRI

remission, defined using 2 validated MRI indices (Clermont score3 and Magnetic

Resonance Index of Activity1), was

associated with sustained clinical remission and decreased risk of surgery for ileal and colonic patients with CD.4The ultimate

results of the Impact of early MRI reMission As therapeutic target in Crohn’s disease pa-tients (IRMA) study, a prospective multi-center cohort aiming to determine the best MRI transmural improvement after anti-tumor necrosis factor therapy to predict sus-tained clinical remission, are eagerly awaited.5We strongly encourage initiatives,

like those from Fernandes et al, attempting to introduce the widespread use of MRI end points in assessing therapeutic efficacy in patients with CD in routine clinical practice.

Anthony Buisson, MD, PhD*,†

Constance Hordonneau, MD‡ Parakkal Deepak, MBBS, MS§ *Université Clermont Auvergne Inserm, 3iHP CHU Clermont-Ferrand Service d’Hépato-Gastro Entérologie Clermont-Ferrand, France

Université Clermont Auvergne

Inserm U1071, M2iSH USC-INRA 2018 Clermont-Ferrand, France

Université Clermont Auvergne

CHU Clermont-Ferrand Service de Radiologie Clermont-Ferrand, France

§Division of Gastroenterology

John T. Milliken Department of Medicine Washington University School of Medicine Saint Louis, Missouri

REFERENCES

1. Ordás I, Rimola J, Rodríguez S, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn’s

disease. Gastroenterology. 2014;146:374–382.e1.

2. Deepak P, Fletcher JG, Fidler JL, et al. Radiological response is associated with better long-term outcomes and is a potential treatment target in patients with

small bowel Crohn’s disease. Am J Gastroenterol.

2016;111:997–1006.

3. Hordonneau C, Buisson A, Scanzi J, et al. Diffusion-weighted magnetic resonance imaging in ileocolonic Crohn’s disease: validation of quantitative index of

activity. Am J Gastroenterol. 2014;109:89–98.

4. Buisson A, Hordonneau C, Goutorbe F, et al. 139-MRI remission after therapeutic intervention is associated with more time spent in clinical corticosteroids-free

remission and decreased risk of surgery in Crohn’s

dis-ease. Gastroenterology. 2017;152:S39–S40. 5. Buisson A, Messadeg L, Bouguen G, et al.

Sa1890-Definition of therapeutic response criteria using MRI in Crohn’s disease patients treated with anti-TNF ther-apy: a Multicenter Prospective Study (the IRMA Study). Gastroenterology. 2017;152:S384.

Reply:

We appreciate the interest and kind and critical comments provided on our study. Cross-sectional imaging is increas-ingly used in patients with Crohn’s dis-ease, not only to define the extension of disease but also to assess local complica-tions. Several studies have suggested that changes in magnetic resonance enterogra-phy (MRE), computed tomograenterogra-phyenter- tomographyenter-ography, and intestinal ultrasound are associated with treatment response.1–3 Therefore, like endoscopy, cross-sectional imaging may hold promise as a therapeutic target in Crohn’s disease.

This led us to develop a retrospective study using a cohort of patients evaluated by MRE and colonoscopy. The main conclusion of our study is that achieving

transmural healing, defined as an endo-scopic and MRE remission, is associated with improved 1-year outcomes (surgery, hospitalization, and therapy escalation), and is superior to achieving mucosal heal-ing alone.

Buisson et al raise several questions about our study. One relates to the interval between MRE and endoscopy. This is understandable, as the gap between ex-aminations may have been enough to lead to improvement or complete resolution of lesions. As stated in the methods of the article, we have included patients with an interval of less than 6 months between MRE and endoscopy. This decision was supported by a subgroup analysis showing no differences in demographics, disease characteristics, or 1-year outcomes between patients with,1, 1 to 3, or 4 to 6 months. Nevertheless, to control for this potential bias, outcomes were assessed from the most recent examination, and pa-tients reaching any of the outcomes between examinations were excluded from the study (meaning that changes in therapy were not allowed between exami-nations). Although we cannot exclude spontaneous variations in inflammatory activity between examinations, we believe that our study design limits the signifi-cance of this potential confounder.

Buisson also raises the question whether differences in disease duration might influence the likelihood of reaching transmural healing or the prevalence of disease-related complications such as stric-tures and fistulas. As we know, Crohn’s disease induces cumulative structural bowel damage, initially characterized by a nonstricturing nonpenetrating behavior with progression over time to a fibrostrictur-ing and/or penetratfibrostrictur-ing phenotype.4,5 If

transmural healing was explained only by disease duration, then it would be expected that patients with transmural have a shorter disease duration. Furthermore, the likeli-hood of achieving transmural healing should decrease over time. Instead, as shown in table 2, demographics and dis-ease characteristics were similar between patients irrespective of the type of healing. Further analysis shows nonsignificant dif-ferences in disease duration between

The authors have no conflict of interest to disclose. Copyright © 2017 Crohn’s & Colitis Foundation DOI 10.1097/MIB.0000000000001227 Published online 3 August 2017.

Inflamm Bowel Dis  Volume 23, Number 9, September 2017 Letters to the Editor

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