David H. Bruining

Development of the Lémann Index to Assess Digestive Tract Damage in Patients With Crohn's Disease

BACKGROUND & AIMSnThere is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohns disease (CD).nnnMETHODSnWe performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods.nnnRESULTSnData from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall.nnnCONCLUSIONSnIn a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment.

Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab†

Background: The aim of this study was to assess the clinical benefit and tolerability of adalimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF), in patients with ulcerative colitis (UC). Methods: Patients with active UC, including those who had lost response or developed intolerance to the chimeric anti‐TNF antibody infliximab, were enrolled in a 24‐week uncontrolled trial. Patients were treated with subcutaneous adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg every other week starting at week 4. After week 8 the dose could be escalated to 40 mg weekly for incomplete response. Outcome measures included clinical response and remission and mucosal healing. Results: Twenty patients were enrolled, of whom 13 had previously received infliximab. Seven patients had dose escalation of adalimumab between weeks 8 and 16, from 40 mg every other week to 40 mg weekly, due to incomplete response. The rates of clinical response were 25% at week 8 and 50% at week 24. The rates of clinical remission were 5% at week 8 and 20% at week 24. The rate of mucosal healing was 30% at week 8. The rates of clinical response and remission and mucosal healing were similar in infliximab‐naïve and previously exposed patients. None of the patients experienced hypersensitivity reactions during treatment with adalimumab. Conclusions: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with UC, including those who have previously lost their response to or cannot tolerate infliximab. (Inflamm Bowel Dis 2009)

New Concepts in Intestinal Imaging for Inflammatory Bowel Diseases

In the last decade, multiple imaging technologies have been developed that improve visualization of the mucosal, mural, and perienteric inflammation associated with inflammatory bowel diseases. Whereas these technologies have traditionally been used to detect and stage suspected enteric inflammation, we review new, emerging roles in detecting clinically occult inflammation (in asymptomatic patients) and inflammatory complications, predicting response prior to therapy, assessing response after therapy, and enteric healing. We compare the relative performance of these technologies in detecting inflammation, focusing on their advantages and disadvantages and how they might complement each other. We also discuss their potential benefits for patients and clinical trials, reviewing technologic developments and areas of research that could provide important insights into the pathophysiology of inflammatory bowel diseases-related enteric inflammation.

Endoscopic Skipping of the Distal Terminal Ileum in Crohn's Disease Can Lead to Negative Results From Ileocolonoscopy

BACKGROUND & AIMSnCrohns disease often involves the terminal ileum (TI), but skipping of the distal TI can occur. This can lead to negative results from ileocolonoscopy. We analyzed advanced cross-sectional images to determine how frequently this occurs.nnnMETHODSnWe analyzed data from 189 consecutive patients (55% women) with Crohns disease, evaluated in 2009 by computed tomography enterography (CTE) and ileocolonoscopy. The discharge impression of the gastroenterologist who treated the patients was used as the reference standard for Crohns disease activity.nnnRESULTSnOf the patients evaluated, 153 underwent TI intubation during endoscopy; 67 of these (43.8%) had normal results from ileoscopy, based on endoscopic appearance. Despite their normal results from ileoscopy, 36 of these patients (53.7%) had active, small-bowel Crohns disease. The ileum appeared normal at ileoscopy because the disease had skipped the distal ileum of 11 patients (30.6%), developed only in the intramural and mesenteric distal ileum of 23 patients (63.9%), and appeared only in the upper gastrointestinal region of 2 patients (5.6%). These patients had a shorter duration of disease (61.1% for less than 5 years) compared with those found to have Crohns disease based on ileoscopy (41.1% for less than 5 years; P < .05). CTE detected extracolonic Crohns disease in 26% of patients; 14% of patients were found to have disorders unrelated to inflammatory bowel disease that warranted further investigation or consultation (including 4 cancers).nnnCONCLUSIONSnIleoscopy examination can miss Crohns disease of the TI because the disease can skip the distal ileum or is confined to the intramural portion of the bowel wall and the mesentery. CTE complements ileocolonoscopy in assessing disease activity in patients with Crohns disease.

Validation of the Ulcerative Colitis Colonoscopic Index of Severity and Its Correlation With Disease Activity Measures

BACKGROUND & AIMSnEndoscopic healing is likely to become an important goal for treatment of patients with ulcerative colitis (UC). A simple validated endoscopic index is needed. We validated the previously developed UC Colonoscopic Index of Severity (UCCIS).nnnMETHODSnIn a prospective study, 50 patients with UC were examined by colonoscopy; we analyzed videos of rectum and sigmoid, descending, transverse, and cecum/ascending colon. Eight gastroenterologists blindly rated 4 mucosal lesions (for vascular pattern, granularity, friability, ulceration) and severity of damage to each segment and overall. The global assessment of endoscopic severity (GAES) was based on a 4-point scale and 10-cm visual analogue scale. Correlation of the UCCIS score with clinical indexes (clinical activity index and simple clinical colitis activity index), patient-defined remission, and laboratory measures of disease activity (levels of C-reactive protein, albumin, and hemoglobin and platelet counts) were estimated by using the Pearson (r) or Spearman (r(s)) method.nnnRESULTSnInterobserver agreement was good to excellent for the 4 mucosal lesions evaluated by endoscopy and the GAES. The UCCIS calculated for our data accounted for 74% (R(2) = 0.74) and 80% (R(2) = 0.80) of the variation in the GAES and visual analogue scores, respectively (P < .0001). The UCCIS also correlated with clinical activity index (r = 0.52, P < .001), simple clinical colitis activity index (r = 0.62, P < .0001), and patient-defined remission (r = 0.43, P < .01). The UCCIS also correlated with levels of C-reactive protein (r(s) = 0.56, P < .001), albumin (r = -0.55, P < .001), and hemoglobin (r = -0.39, P < .01). A rederivation of the equation for the UCCIS by using the data from a previous study combined with those of the current study (n = 101) yielded similar results.nnnCONCLUSIONSnThe UCCIS is a simple tool that provides reproducible results in endoscopic scoring of patients with UC.

Benefit of computed tomography enterography in Crohn's disease: Effects on patient management and physician level of confidence

Background: Computed tomographic enterography (CTE) has been shown to have a high sensitivity and specificity for active small bowel inflammation. There are only sparse data on the effect of CTE results on Crohns disease (CD) patient care. Methods: We prospectively assessed 273 patients with established or suspected CD undergoing a clinically indicated CTE. Providers were asked to complete pre‐ and postimaging questionnaires regarding proposed clinical management plans and physician level of confidence (LOC) for the presence or absence of active small bowel disease, fistula(s), abscess(es), or stricturing disease. Correlative clinical, serologic, and histologic data were recorded. Following revelation of CTE results, providers were questioned if CTE altered their management plans, and whether LOC changes were due to CTE findings (on a 5‐point scale). Results: CTE altered management plans in 139 cases (51%). CTE changed management in 70 (48%) of those with established disease, prompting medication changes in 35 (24%). Management changes were made post‐CTE in 69 (54%) of those with suspected CD, predominantly due to excluding CD (36%). CTE‐perceived changes in management were independent of clinical, serologic, and histologic findings (P < 0.0001). Clinically meaningful LOC changes (2 or more points) were observed in 212 (78%). Conclusions: CTE is a clinically useful examination, altering management plans in nearly half of patients with CD, while increasing physician LOC for the detection of small bowel inflammation and penetrating disease. These findings further support the use of CTE in CD management algorithms. (Inflamm Bowel Dis 2011;)

Computed Tomography Enterography Detects Intestinal Wall Changes and Effects of Treatment in Patients With Crohn's Disease

BACKGROUND & AIMSnThe use of computed tomography enterography (CTE) in patients with Crohns 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.nnnMETHODSnWe performed a retrospective study of patients with Crohns 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, 215-630).nnnRESULTSnOf 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 (κ = 0.26, 0.07, and 0.30 respectively).nnnCONCLUSIONSnRadiologic improvement was observed in 63.4% of patients with Crohns 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.

Anti-tumour necrosis factor treatment of inflammatory bowel disease in liver transplant recipients

Ulcerative colitis (UC) and Crohns disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (OLT) despite post‐transplantation immunosuppressive therapy.

Similar Outcomes of Surgical and Medical Treatment of Intra-abdominal Abscesses in Patients With Crohn's Disease

BACKGROUND & AIMSnIt is not clear whether medical therapy, surgery, or both is the best approach for patients with Crohns disease who develop an intra-abdominal abscess.nnnMETHODSnWe evaluated data from patients with Crohns disease who were diagnosed with a radiologically confirmed abdominal abscess (enhancing fluid collection, ≥ 1 cm) from 1999 to 2006 (n = 95; median age, 42.0 y; 50.5% female). Medical/nonsurgical methods (percutaneous aspiration ± drain placement) were used for 55 patients (mean abscess size, 6.9 ± 3.2 cm), and 40 patients underwent surgical interventions (laparotomy ± bowel resection; mean abscess size, 7.5 ± 3.7 cm). We investigated risk factors for abscess recurrence.nnnRESULTSnThe median length of hospitalization was 15.5 days for patients who underwent surgery and 5.0 days for patients who did not (P < .001). The 5-year cumulative probability of abscess recurrence was 31.2% among patients who did not undergo surgery and 20.3% among those who did (P = .25). Histories of perianal or active ileal disease predicted abscess recurrence. Initiation of pharmacologic therapy after drainage reduced the risk for abscess recurrence (P < .001). Anti-tumor necrosis factor therapy, compared with no therapy, reduced the risk of abscess recurrence (P = .001) in all patients, whereas immunosuppressive monotherapy, compared with no therapy, had a trend toward significant risk reduction (P = .06).nnnCONCLUSIONSnAmong patients with Crohns disease who have intra-abdominal abscesses, nonsurgical and primary surgical management strategies result in similar rates of abscess recurrence and complications. Initiation of anti-tumor necrosis factor and/or immunosuppressive therapy when abscesses resolve might protect against intra-abdominal penetrating disease.

A Model for Identifying Cytomegalovirus in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMSnThe presentation of cytomegalovirus (CMV) disease in patients with inflammatory bowel disease (IBD) can be similar to that of idiopathic IBD. It is a challenge to identify patients at highest risk for CMV. We investigated risk factors and generated a clinical score to identify patients with IBD at highest risk for CMV disease.nnnMETHODSnWe performed a retrospective case-control study of 68 patients with IBD (66% with ulcerative colitis, 31% with Crohns disease, and 3% with unclassified IBD) diagnosed with CMV disease on the basis of tissue analysis from January 2005 through December 2011 at Mayo Clinic, Rochester. The patients were each matched with 3 patients with IBD and suspected CMV disease (controls). An a priori set of the most objective variables was used to create a model to identify those with CMV disease. Scores were assigned to each significant factor from the multivariable analysis. Cutoff values that identified patients with CMV with ≥85% sensitivity and specificity were selected.nnnRESULTSnPatients with medically refractory IBD (odds ratio [OR], 3.69; P < .001) or endoscopic ulcers (OR, 3.06; P < .001) and those treated with corticosteroids (OR, 2.95; P < .001) or immunomodulators (OR, 1.86; P = .030) but not tumor necrosis factor antagonists (OR, 1.30; P = .376) were more likely to have CMV disease than patients with IBD without these features. In a multivariable model, refractory disease, treatment with immunomodulators, and age older than 30 years were independently associated with CMV disease. Use of tumor necrosis factor antagonists was an insignificant factor even after adjustment.nnnCONCLUSIONSnClinical features can identify patients with IBD at risk for CMV disease. This model may help clinicians stratify patients on the basis of risk when CMV disease is suspected.