The medical management of Crohn s disease remains a

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9: Computed Tomography Enterography Detects Intestinal Wall Changes and Effects of Treatment in Patients With Crohn s Disease DAVID H. BRUINING,* EDWARD V. LOFTUS JR,* ERIC C. EHMAN, HASSAN A. SIDDIKI, DOUGLAS L. NGUYEN,* JEFF L. FIDLER, JAMES E. HUPRICH, JAYAWANT N. MANDREKAR, WILLIAM S. HARMSEN, WILLIAM J. SANDBORN,* and JOEL G. FLETCHER *Division of Gastroenterology and Hepatology, Department of Radiology, and Division of Biostatistics, Mayo Clinic, Rochester, Minnesota BACKGROUND & AIMS: The use of computed tomography enterography (CTE) in patients with Crohn s disease has increased. However, there is little data available on how radiologic parameters of active disease change during treatment with infliximab and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. METHODS: We performed a retrospective study of patients with Crohn s disease who had undergone serial CTE imaging while receiving infliximab. Lesions were defined as improved if their enhancement or length decreased without worsening of other parameters. Patients were grouped as responders (all lesions improved), partial responders (some lesions improved), and nonresponders (worsening or no changes in all lesions). Of the 63 patients identified (47% female), the median age was 37.7 years, the median disease duration was 7.6 years, and the median time between initial and first follow-up CTE was 356 days (interquartile range, ). RESULTS: Of 105 lesions, 52 (49.5%) improved, 11 (10.5%) remained unchanged, and 42 (40.0%) worsened. Per patient, 28 (44.4%) were responders, 12 (19.0%) were partial responders, and 23 (36.5%) were nonresponders. The radiologic response had poor-to-fair agreement with symptoms, endoscopic appearance, and levels of C-reactive protein at time of second CTE ( 0.26, 0.07, and 0.30 respectively). CONCLUSIONS: Radiologic improvement was observed in 63.4% of patients with Crohn s disease who received infliximab therapy, despite a study design that was likely biased toward nonresponders. Radiologic response was not in good agreement with clinical symptoms, serum biomarkers, or endoscopic appearance; CTE might be used as a complementary approach to identify mural healing or inflammation not detected by other methods. Keywords: Intestinal Wall Changes; Inflammatory Bowel Disease; IBD; Imaging. The medical management of Crohn s disease remains a clinical challenge. Objectively assessing response to therapy has become an important concept, as the early use of therapies effective for the endpoints of both symptomatic remission and bowel healing may be critical in altering the natural history of the disease. 1,2 Individualized optimized care is needed as not all patients will respond to the same medical regime, and clinical symptoms correlate poorly with biological activity. Persistent inflammation is a risk factor for disease progression to complications and surgery. 3,4 Serial assessment of disease activity allows clinicians to identify patients who continue to have active inflammation despite symptomatic improvement or remission. It also identifies patients who have had resolution of inflammation despite ongoing symptoms, suggesting the presence of undiagnosed comorbidities. 5 Small intestinal Crohn s disease activity can be difficult to objectively assess. Symptom-based disease activity indexes are subjective by design and often unreliable. 6 Endoscopy can evaluate the small intestine for mucosal healing but it is invasive, expensive, exposes patients to inherent procedural risks, and may not always be feasible depending on the disease location. 7 Diagnostic modalities that can serve as an alternative or an adjunct to ileocolonoscopy to evaluate therapeutic response and guide management decisions are needed. Computed tomography enterography (CTE) or magnetic resonance enterography (MRE) could potentially serve this purpose as they are noninvasive imaging modalities that can assess transmural healing. Both techniques use a large volume of negative or neutral oral contrast to improve small bowel mural evaluations. 8 CTE is highly sensitive and specific for active small intestinal inflammation, setting it apart from other tests such as capsule endoscopy. 9,10 CTE and MRE perform similarly in the assessment of disease, but interobserver agreement and image quality may be superior with CTE. 10 These characteristics likely explain recent data demonstrating that CTE changes clinicians perception regarding the benefit of steroids, alters management plans, and improves physician level of confidence for the presence of active disease. 11,12 Hara and colleagues have also reported in a small group of Crohn s disease patients that CTE can potentially be used to follow patients longitudinally, noting it reliably predicted disease progression or regression. 13 We sought to explore how computed tomography (CT) radiologic parameters of active inflammation change over time during medical therapy with an anti-tumor necrosis factor (TNF) alpha agent, infliximab. There is a paucity of data as to how and when imaging measures of inflammation may change with therapy. We also sought to examine whether radiologic response correlates with improved clinical symptoms, serum biomarkers, and endoscopic appearance. Abbreviations used in this paper: CRP, C-reactive protein; CT, computed tomography; CTE, computed tomography enterography; IBD, inflammatory bowel disease; IQR, interquartile range; MRE, magnetic resonance enterography; TNF, tumor necrosis factor by the AGA Institute /$36.00 doi: /j.cgh

2 680 BRUINING ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 9, No. 8 Methods Study Design and Population We retrospectively identified 63 consecutive patients with established Crohn s disease who underwent serial CTE imaging while being treated with infliximab at Mayo Clinic, Rochester, Minnesota, between September 18, 2002 and December 31, To be included in the study, patients had either CT imaging before and after initiation of infliximab, or 2 CTEs more than 6 months apart while using infliximab for maintenance therapy. This retrospective study was approved by the Mayo Clinic Institutional Review Board. Definitions Established Crohn s disease was defined as a diagnosis of Crohn s disease after evaluation by a gastroenterologist or a colorectal surgeon. The subset of maintenance therapy study patients had been using infliximab for more than 12 weeks before the initial CTE was performed. Disease duration was calculated based on the date at which symptoms first appeared. Penetrating disease was defined as an abscess, phlegmon, or fistula, excluding patients with isolated perianal disease. CTE imaging was performed as previously described using a large volume of oral neutral enteric contrast, iodinated intravenous contrast, and high spatial resolution imaging of the abdomen and pelvis in multiple planes. 14 All patients were scanned in the enteric phase (45 50 seconds after injection of iodinated contrast dye) at all time points, 8,15 except for 3 patients undergoing 4 CTEs that were scanned in the portal phase (70 seconds after injection of iodinated contrast dye). Patients included at the beginning of the study received 1500 ml oral methylcellulose solution supplemented by oral metoclopramide and intravenous glucagon. In 2004, we changed our oral contrast regimen to 1350 ml of low contrast barium suspension (Volumen; Bracco Diagnostics, Princeton, New Jersey) followed by 500 ml of water. Information was collected both per lesion and per patient. Lesions were considered distinct if they were separated by a region with normal imaging features. Improved lesions were those that demonstrated a decrease in enhancement or length, without worsening of the other parameters (enhancement, length, dilated vasa recta/comb sign, fatty proliferation, or stratification). Worsened lesions were those with an increase in any imaging parameter of active inflammation (enhancement, length, dilated vasa recta/comb sign, fatty proliferation, or stratification). Unchanged lesions were those without worsening parameters without meeting criteria for improved status. Patients were classified as responders if all lesions improved, partial responders if some lesions improved, and nonresponders if worsening or no change was detected in all lesions. Responder status was based on comparison with second CTE. In order to remain in the responder group, no worsening could be identified on CTEs subsequent to the initial follow-up examination. Data Collection Information for each patient was obtained by review of the medical record. This included laboratory testing and endoscopy reports. A gastroenterologist with a subspecialty in the treatment of inflammatory bowel disease, blinded to the imaging results, characterized each patient as improved, no change, or worsened based on a review of medical records and the managing gastroenterologist s impression at the time of follow-up imaging. This was performed both for clinical symptoms as well as endoscopic appearance. Data were also collected on imaging indication, lesion location, and concomitant inflammatory bowel disease (IBD) medication usage. Radiologic scoring was performed by a gastrointestinal radiologist blinded to the clinical, laboratory, and endoscopic data. The radiologists were not blinded to the previous images as comparisons were needed to assure that the same segment of small bowel was being reassessed. Enhancement, comb sign (dilated vasa recta), stratification, and fatty proliferation were scored on a 5-point scale (0 none, 1 equivocal, 2 mild, 3 moderate, 4 severe). Bowel length was given in centimeters (cm) and wall thickness was provided in millimeters (mm). Centripetal healing was defined as that which occurs from the ends toward the center of a lesion, without a requirement that healing segments be continuous. Statistical Analysis Descriptive statistics were reported as number (percent), or median (interquartile range [IQR]) as appropriate. CTE response to infliximab was categorized as complete or partial versus no response. Kappa statistics were estimated for agreement between CTE response, clinical symptoms, C-reactive protein (CRP), and endoscopic appearance. Kappa values were defined as: poor (less than 0.20); fair ( ); moderate ( ); good ( ); and very good ( ). Univariate logistic regression was performed to assess the association between baseline patient characteristics and radiologic response. Odds ratios and 95% confidence intervals based on logistic regression model estimates were reported. The alphalevel was set at.05 for statistical significance. Results A total of 65 consecutive patients were identified. Of this group, 2 patients were excluded, as all follow-up imaging was only with MRE. Of the 63 patients included in the analysis, women comprised 47.2% of the cohort (Table 1). The median age was 37.7 years (IQR, years), the median disease duration was 7.6 years (IQR, years), and the median time between index and second CTE was 356 days (IQR, days). Imaging was only performed on patients during maintenance therapy in 27.0% (n 17). In those patients with index CTE before initiation of infliximab, the median time between CTE and first dose of infliximab was 11 days (IQR, 1 77 days). In those undergoing serial CTEs 6 months or more apart during maintenance therapy, the median interval between starting infliximab and index CTE was 355 days (IQR, days). A history of IBD-related surgery was noted in 63.4% (n 40), a history of perianal disease was reported in 65.1% (n 41), and a history of internal penetrating disease was described in 33.3% (n 21). CRP was elevated above the upper limit of normal (0.8 mg/dl) in 41.1% (n 23) of patients at the time of the initial CTE. The most frequent initial indication for imaging was abdominal pain (68.9%) (Table 2). For follow-up imaging evaluations, the most common indication was to reassess disease activity (79.3% 100%). More than 2 CTEs were performed in 30.2% of patents, with 1 individual having undergone 5 CTEs. Three or

3 August 2011 INTESTINAL WALL CHANGES WITH INFLIXIMAB 681 Table 1. Demographic and Clinical Characteristics of Study Patients Total patients Complete responders (n 28) Partial responders (n 12) Nonresponders (n 23) Women, n (%) 30 (47.2) 16 (57.1) 4 (33.3) 10 (43.4) Age at first CTE, y, median (IQR) 37.7 ( ) 34.2 ( ) 42.0 ( ) 40.8 ( ) Disease duration, y, median (IQR) 7.6 ( ) 6.8 ( ) 10.6 ( ) 7.4 ( ) Time between index and second CTE, d, median (IQR) 356 ( ) 361 ( ) 348 ( ) 294 ( ) Imaging during anti-tnf maintenance therapy, n (%) a 17 (27.0) 4 (14.3) 4 (33.3) 9 (39.1) History of IBD surgery, n (%) b 40 (63.4) 16 (57.1) 10 (83.3) 14 (60.9) History of perianal disease, n (%) 41 (65.1) 18 (64.3) 7 (58.3) 16 (70.0) History of internal penetrating disease, n (%) 21 (33.3) 9 (32.1) 4 (41.7) 7 (30.4) Individuals with more than 2 CTEs, n (%) 19 (30.2) 5 (17.9) 4 (33.3) 10 (43.5) a Maintenance defined as having had serial CTE imaging only after at least 12 weeks of infliximab therapy. b IBD surgery defined as previous small bowel resection, stricturoplasty, or colonic resection. more CTEs were more commonly performed in nonresponders (43.5%) compared with complete (17.9%) or partial (33.3%) responders (Table 1). Of the 105 lesions detected, the majority were located in the ileum or ileocecal region (75.2%) (Supplementary Table 1). Six lesions occurred at a surgical anastomosis and 2 individuals had isolated colonic abnormalities. Most patients were taking immunomodulators, 6-mercaptopurine or azathioprine, at the time of initial (81.0%) and follow-up imaging (84.1%) (Table 3). Response rates were assessed both per lesion (n 105) and per patient. Of the lesions, 49.5% (n 52) improved, 10.5% (n 11) were unchanged, and 40.0% (n 42) worsened (Table 4). Per patient, 44.4% (n 28) were complete responders, 19.0% (n 12) were partial responders, and 36.5% (n 23) were nonresponders. Healing often occurred in a centripetal fashion (Supplementary Figure 1). Of the complete responders, 25.0% (n 7) had normalization of all CTE abnormalities during infliximab therapy (Supplementary Figure 2). Of the lesions (n 37) in the complete responders, improvement was noted in length of segment (81.1%), enhancement (75.7%), stratification (51.4%), fatty proliferation (16.2%), and comb sign (56.8%). We sought to further explore correlations with CTE findings and possible predictors of radiologic response. Poor to fair correlation was noted between CTE response and improved clinical symptoms ( 0.26), improved endoscopic appearance ( 0.07), and reduction of CRP ( 0.30) (Table 5). In comparing responders (complete and partial) with nonresponders, only the presence of comb sign on the index CTE was predictive of radiologic response (P.024) (Table 6). Patients with a history of perianal disease (odds ratio, 0.2; P.05) were less likely to be a partial or complete radiologic responder. Discussion This study demonstrates that radiologic response is noted in more than 60% of patients using infliximab therapy. This result may be an underestimation of response given that the study design was likely biased toward nonresponders. Often serial imaging has been reserved in clinical practice for reassessing patients who continue to do poorly (remain symptomatic) despite aggressive medical care. In that context, one would have expected to include a large number of nonresponders in this retrospective analysis. Despite this limitation, our research suggests a radiologic response in the majority of patients receiving combination therapy with infliximab and an immunomodulator. Radiologic responses included normalization of enhancement, reduction in length of disease, and resolution of the comb sign, stratification, and perienteric fat stranding. We used the imaging parameters of mural enhancement and length of disease to define lesion response to therapy. Enhancement was selected as 1 of our parameters of interest, because multiple studies have now described an excellent agreement between mural enhancement and active intestinal inflammation. 8,16 Length of disease was used as a measure of disease burden. We choose not to include mural thickness in our criteria for lesion response, as it is heavily dependent on the degree of bowel distention with oral contrast, a feature which can be quite variable in clinical practice. Poor to fair agreement was identified between radiologic improvement and clinical symptoms, reductions in CRP, and improved endoscopic appearance. The reason for this finding is likely inherent to the limitations of each parameter. Clinical symptoms are often unreliable, noting a large functional disease overlap, as well the high prevalence of small bowel bacterial overgrowth and bile salt diarrhea. 17 Serum CRP levels have been shown to correlate with fatty proliferation, but agreement with other radiologic features has been less robust. 18,19 Endoscopy remains the gold standard for the assessment of mucosal healing; however, Crohn s disease is a transmural process and lesions may be located in regions inaccessible to standard endoscopy. Cross-sectional imaging such as CTE and MRE may Table 2. Indications for CT Enterography Indication First CTE Second CTE Third CTE (n 21) Fourth CTE (n 3) Fifth CTE (n 1) Abdominal pain 44 (68.9) 11 (17.5) 1 (4.8) 1 (33.3) 0 (0.0) Reassess disease activity 12 (19.0) 50 (79.3) 19 (90.4) 2 (66.7) 1 (100.0) Fever/mass/concern for penetrating disease 7 (11.1) 2 (3.2) 1 (4.8) 0 (0.0) 0 (0.0) NOTE. Data are n (%).

4 682 BRUINING ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 9, No. 8 Table 3. Non Anti-TNF IBD Medications at Time of CTE Medications First CTE Second CTE None 2 (3.2) 6 (9.5) Mesalamine 1 (1.6) 0 (0.0) Azathioprine/6-mercaptopurine 51 (81.0) 53 (84.1) Methotrexate 2 (3.2) 4 (6.3) Prednisone 6 (9.5) 0 (0.0) Budesonide 1 (1.6) 0 (0.0) NOTE. Data are n (%). Table 5. Agreement of Radiologic Response a With Improved Clinical Symptoms, Endoscopic Appearance, or Serum Biomarkers Kappa 95% CI Improved clinical symptoms Improved endoscopic appearance to 0.44 Reduction in CRP CI, confidence interval. a Radiologic response for this analysis defined as individuals with improvement in all or some lesions at time of second CTE. provide a more global transmural evaluation of the intestinal wall. These factors may in part explain the low levels of agreement observed in our study, and support the notion of CTE as a complementary tool in disease activity assessments. We also sought to identify potential patient and imaging features associated with a radiologic response. The only marker with a positive predictive value was the presence of comb sign on the initial CTE. Patients with a history of perianal disease had a lower likelihood of being a complete or partial radiologic responder. Caution should be used when interpreting this somewhat unexpected finding. Most of the patients with a history of perianal disease were also imaged strictly during maintenance therapy. When our analysis was restricted to only those with CTE imaging before and after infliximab therapy initiation (n 46), a history of perianal disease was not a significant predictor. Lower response rates in patients already using maintenance therapy suggest that early bowel wall changes, not captured because of the absence of a pre-infliximab CTE, may have occurred. These findings need to be confirmed by additional studies. A minority of patients received CTE examinations that differed in acquisition parameters from the majority of patients, relating to the phase of contrast enhancement or oral contrast delivery at the beginning of our study. However, Vandenbroucke et al performed a multireader assessment of inflammatory findings on CTE in patients undergoing biphase CTE (in the enteric and portal phases) and found no difference in identifying enteric inflammation for any reader between these 2 phases. 20 The change in oral contrast from methylcellulose solution to low-concentration barium solution oral contrast (Volumen; Bracco Diagnostics) should have improved small bowel distention, 21 consequently improving the ability to identify residual inflammation. Several limitations to this work are apparent. First, while radiologic response was noted in more then 60% of patients, the significance of this finding is not fully known. While ongoing Table 4. Response Rates Based on Serial CTE Imaging Radiologic response Number (%) Per lesion (n 105) Improved 52 (49.5) Unchanged 11 (10.5) Worsened 42 (40.0) Per patient Complete responders 28 (44.4) Partial responders 12 (19.0) Nonresponders 23 (36.5) inflammation is a marker for progression to complications and surgery, it is not yet known if therapy directed at radiologic end points can alter the natural history of the disease. Second, the question of when bowel wall healing occurs with treatment cannot be answered by this retrospective data. Third, the absence of a control group does not allow us to explore any dynamic radiologic changes that may occur independent of medical therapy. While all the study patients did receive infliximab, confounding factors from concomitant medications cannot be fully excluded. Finally, clinical assessment scales could have been used to compare clinical symptoms and radiologic response; however, given our retrospective design and difficulty obtaining all the parameters to generate these scales, we chose to use the clinical impression of the gastroenterologist who was managing each patient. These issues will likely need to be explored in a prospective fashion, using MRE or low-dose CTE because of ionizing radiation concerns. These results, however, provide the background and justification with moving forward with such a project. In conclusion, CTE-based radiologic response was noted in more than 60% of patients using infliximab therapy. Poor to fair agreement with clinical symptoms, serum biomarkers, and endoscopic appearance highlights the role of CTE as a complementary modality. Bowel wall healing appears to occur in a Table 6. Odds of Complete or Partial Radiologic Response Versus Nonresponse Based on Characteristics at Time of First CTE Variables at index CTE (n 63 patients) Odds ratio 95% CI P value Age, per 1 y Female Disease duration, per 1 y History of perianal disease History of internal penetrating disease Abnormal CRP a Length, per 1 cm Enhancement (moderate-severe) b Presence of stratification Thickness, per 1 mm Presence of fibrofatty proliferation Presence of comb sign CI, confidence interval. a Greater than 8 mg/l. b Moderate-severe enhancement defined as a score of 3 or 4 (scale 0 4).

5 August 2011 INTESTINAL WALL CHANGES WITH INFLIXIMAB 683 centripetal fashion, and complete normalization of CTE findings can occur with infliximab therapy. Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at and at doi: / j.cgh References 1. Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn s disease. Inflamm Bowel Dis 2002;8: D Haens GR, Fedorak R, Lémann M, et al. Endpoints for clinical trials evaluating disease modification and structural damage in adults with Crohn s disease. Inflamm Bowel Dis 2009;15: Frøslie KF, Jahnsen J, Moum BA, et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian populationbased cohort. Gastroenterology 2007;133: Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn s disease. Gastroenterology 2004;126: Sandborn WJ. How to avoid treating irritable bowel syndrome with biologic therapy for inflammatory bowel disease. Dig Dis 2009;27 Suppl 1: Freeman HJ. Limitations in assessment of mucosal healing in inflammatory bowel disease. World J Gastroenterol 2010;16: Terheggen G, Lanyi B, Schanz S, et al. Safety, feasibility, and tolerability of ileocolonoscopy in inflammatory bowel disease. Endoscopy 2008;40: Booya F, Fletcher JG, Huprich JE, et al. Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Radiology 2006;241: Solem CA, Loftus EV Jr., Fletcher JG, et al. Small-bowel imaging in Crohn s disease: a prospective, blinded, 4-way comparison trial. Gastrointest Endosc 2008;68: Siddiki HA, Fidler JL, Fletcher JG, et al. Prospective comparison of state-of-the-art MR enterography and CT enterography in smallbowel Crohn s disease. AJR Am J Roentgenol 2009;193: Higgins PD, Caoili E, Zimmermann M, et al. Computed tomographic enterography adds information to clinical management in small bowel Crohn s disease. Inflamm Bowel Dis 2007;13: Bruining DH, Siddiki H, Fletcher JG, et al. Clinical benefit of CT enterography in suspected or established Crohn s disease: impact on patient management and physician level of confidence. Gastroenterology 2008;134 (Suppl 1):S Hara AK, Alam S, Heigh RI, et al. Using CT enterography to monitor Crohn s disease activity: a preliminary study. AJR Am J Roentgenol 2008;190: Siddiki H, Fletcher JG, Hara AK, et al. Validation of a lower radiation computed tomography enterography imaging protocol to detect Crohn s disease in the small bowel. Inflamm Bowel Dis 2011;17: Schindera ST, Nelson RC, DeLong DM, et al. Multi-detector row CT of the small bowel: peak enhancement temporal window-- initial experience. Radiology 2007;243: Bodily KD, Fletcher JG, Solem CA, et al. Crohn disease: mural attenuation and thickness at contrast-enhanced CT enterography--correlation with endoscopic and histologic findings of inflammation. Radiology 2006;238: Freeman HJ. Use of the Crohn s disease activity index in clinical trials of biological agents. World J Gastroenterol 2008;14: Colombel JF, Solem CA, Sandborn WJ, et al. Quantitative measurement and visual assessment of ileal Crohn s disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein. Gut 2006;55: Solem CA, Loftus EV Jr, Tremaine WJ, et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis 2005;11: Vandenbroucke F, Mortelé KJ, Tatli S, et al. Noninvasive multidetector computed tomography enterography in patients with smallbowel Crohn s disease: is a 40-second delay better than 70 seconds? Acta Radiol 2007: Young BM, Fletcher JG, Booya F, et al. Head-to-head comparison of oral contrast agents for cross-sectional enterography: small bowel distention, timing, and side effects. J Cat 2008;32: Reprint requests Address requests for reprints to: David H. Bruining, MD, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, Minnesota bruining. david@mayo.edu; fax: (507) Conflicts of interest The authors disclose the following: D. Bruining has received research support from Centocor Ortho Biotech; W. Sandborn has received research support from and served as a consultant for Centocor Ortho Biotech; E. Loftus has consulted for Centocor Ortho Biotech (fees to Mayo Clinic); and J. Fletcher has received research support in the past from Siemens Medical Solutions, E-Z-EM, and General Electric. The remaining authors disclose no conflicts. Funding This report was supported by an investigator-initiated grant from Centocor Ortho Biotech.

6 August 2011 INTESTINAL WALL CHANGES WITH INFLIXIMAB 683.e1 Supplementary Table 1. Lesion Location Based on Initial CTE Lesion location n (%) Duodenum 0 (0) Jejunum 5 (4.8) Ileum 61 (58.1) Ileocecal 18 (17.1) Colonic 21 (20.0) Total 105 Supplementary Figure 1. Serial CTE imaging noting centripetal healing with a reduction in enhancement and bowel wall thickness on infliximab therapy. Supplementary Figure 2. Serial CTE imaging demonstrating near complete normalization of abnormalities on infliximab therapy. Initial image (2004) was just prior to initiation of infliximab. Arrows demonstrate regions of asymmetric mural hyperenhancement and luminal stenosis.