Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn's Disease: A Multicenter Study.

BACKGROUND & AIMS: Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. METHODS: In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. RESULTS: We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. CONCLUSIONS: Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Clinical Benefit of Capsule Endoscopy in Crohn's Disease: Impact on Patient Management and Prevalence of Proximal Small Bowel Involvement.

Background: Ileocolonoscopy and computed tomography (CT) or magnetic resonance (MR) enterography (CTE/MRE) are utilized to evaluate patients with small bowel (SB) Crohn's disease (CD). The purpose of our study was to estimate the impact of capsule endoscopy (CE) on patient management after clinical assessment, ileocolonoscopy, and CTE/MRE. Methods: We prospectively analyzed 50 adult CD patients without strictures at clinically indicated ileocolonoscopy and CTE/MRE exams. Providers completed pre- and post-CE clinical management questionnaires. Pre-CE questionnaire assessed likelihood of active SBCD and management plan using a 5-point level of confidence (LOC) scales. Post-CE questionnaire assessed alteration in management plans and contribution of CE findings to these changes. A change of ≥2 on LOC scale was considered clinically meaningful. Results: Of the 50 patients evaluated (60% females), median age was 38 years, median disease duration was 3 years, and median Crohn's Disease Activity Index (CDAI) score was 238 points. All CTE/MRE studies were negative for proximal disease. CE detected proximal disease in 14 patients (28%) with a median Lewis score of 215 points. CE findings altered management in 17 cases (34%). The most frequent provider-perceived benefits of CE were addition of new medication (29%) and exclusion of active SB mucosal disease (24%). Conclusion: CE is a safe imaging modality that alters clinical management in patients with established SBCD by adding incremental information not available at ileocolonoscopy and cross-sectional enterography.

Predictors of Durability of Radiological Response in Patients With Small Bowel Crohn's Disease.

Background: The long-term significance of radiological transmural response (TR) as a treatment goal at the first follow-up scan in small bowel Crohn's disease (CD) has been previously shown. We examined the durability of a long-term strategy of treating to a target of radiological TR and the influence of baseline predictors on the maintenance of TR. Methods: Small bowel CD patients between January 1, 2002, and December 31, 2014, were identified with serial computed tomography enterography (CTE)/magnetic resonance enterography (MRE) before and after initiation of therapy or on maintenance therapy. Overall TR (inflammatory lesions with/without strictures) w1as characterized by abdominal radiologists in up to 5 small bowel lesions per patient at each serial scan until last follow-up or small bowel resection, as response, partial response, or nonresponse. The rate of conversion between TR states and transition to surgery, including the effect of baseline patient/disease characteristics, was examined using a multistate model (mstate R-package). Results: CD patients (n = 150, 705 CTE/MRE) with a median of 4 CTE/MRE during 4.6 years of follow-up, 49% with ileal-only distribution, had 260 examined bowel segments. Conversion from response to partial response/nonresponse was 37.4% per year of follow-up with no transitions seen directly from response to surgery. Current smoking status (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.1-4.3) and internal penetrating disease at baseline scan (HR, 2.2; 95% CI, 1.2-4.1) were associated with a 2-fold increased risk of transition from partial response/nonresponse to surgery. Conclusions: Achievement and maintenance of radiological response is associated with avoidance of small bowel surgery. Continued follow-up with CTE/MRE is recommended to identify loss of response, especially in current smokers and patients with internal penetrating disease at baseline CTE/MRE.

Assessment of multi-modality evaluations of obscure gastrointestinal bleeding.

AIM: To determine the frequency of bleeding source detection in patients with obscure gastrointestinal bleeding (OGIB) who underwent double balloon enteroscopy (DBE) after pre-procedure imaging [multiphase computed tomography enterography (MPCTE), video capsule endoscopy (VCE), or both] and assess the impact of imaging on DBE diagnostic yield. METHODS: Retrospective cohort study using a prospectively maintained database of all adult patients presenting with OGIB who underwent DBE from September 1st, 2002 to June 30th, 2013 at a single tertiary center. RESULTS: Four hundred and ninety five patients (52% females; median age 68 years) underwent DBE for OGIB. AVCE and/or MPCTE performed within 1 year prior to DBE (in 441 patients) increased the diagnostic yield of DBE (67.1% with preceding imaging vs 59.5% without). Using DBE as the gold standard, VCE and MPCTE had a diagnostic yield of 72.7% and 32.5% respectively. There were no increased odds of finding a bleeding site at DBE compared to VCE (OR = 1.3, P = 0.150). There were increased odds of finding a bleeding site at DBE compared to MPCTE (OR = 5.9, P < 0.001). In inpatients with overt OGIB, diagnostic yield of DBE was not affected by preceding imaging. CONCLUSION: DBE is a safe and well-tolerated procedure for the diagnosis and treatment of OGIB, with a diagnostic yield that may be increased after obtaining a preceding VCE or MPCTE. However, inpatients with active ongoing bleeding may benefit from proceeding directly to antegrade DBE.

Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease.

OBJECTIVES: Crohn's disease (CD) management targets mucosal healing on ileocolonoscopy as a treatment goal. We hypothesized that radiologic response is also associated with better long-term outcomes. METHODS: Small bowel CD patients between 1 January 2002 and 31 October 2014 were identified. All patients had pre-therapy computed tomography enterography (CTE)/magnetic resonance enterography (MRE) with follow-up CTE or MRE after 6 months, or 2 CTE/MREs≥6 months apart while on maintenance therapy. Radiologists characterized inflammation in up to five small bowel lesions per patient. At second CTE/MRE, complete responders had all improved lesions, non-responders had worsening or new lesions, and partial responders had other scenarios. CD-related outcomes of corticosteroid usage, hospitalization, and surgery were assessed using Kaplan-Meier survival analysis and multivariable Cox models. RESULTS: CD patients (n=150), with a median disease duration of 9 years, had 223 inflamed small bowel segments (76 with strictures and 62 with penetrating, non-perianal disease), 49% having ileal distribution. Fifty-five patients (37%) were complete radiologic responders, 39 partial (26%), and 56 non-responders (37%). In multivariable Cox models, complete and partial response decreased risk for steroid usage by over 50% (hazard ratio (HR)s: 0.37 (95% confidence interval (CI), 0.21-0.64); 0.45 (95% CI, 0.26-0.79)), and complete response decreased the risk of subsequent hospitalizations and surgery by over two-thirds (HRs: HR, 0.28 (95% CI, 0.15-0.50); HR, 0.34 (95% CI, 0.18-0.63)). CONCLUSIONS: Radiological response to medical therapy is associated with significant reductions in long-term risk of hospitalization, surgery, or corticosteroid usage among small bowel CD patients. These findings suggest the significance of radiological response as a treatment target.

Retained Capsule Endoscopy in a Large Tertiary Care Academic Practice and Radiologic Predictors of Retention.

BACKGROUND: Capsule retention reported rates range between 1% and 13%. This study aims to determine the incidence of, risk factors for, and clinical outcomes of capsule retention in a large heterogenous cohort of patients and define cross-sectional imaging findings predictive of capsule retention. METHODS: A retrospective review of all capsule endoscopy (CE) examinations performed at our center from January 2002 to January 2013 was undertaken. Data on patient demographics, CE indication, findings, and details of management were analyzed. Radiologic images of patients with computed tomography scan performed 6 months before CE for patients with CE retention and for controls without CE retention but at high risk based on clinical computed tomography reports were examined by a gastrointestinal radiologist, blinded to history, and classified as worrisome based on the presence of stricture, partial obstruction, or small bowel (SB) anastomosis. RESULTS: Seventeen CE retentions (0.3%) occurred in 15 patients. Obscure gastrointestinal bleeding (47%) was the most common indication. Outcomes included surgical intervention (n = 10), endoscopic retrieval (n = 2), passing of capsule after treatment of inflammation (n = 3), passage after conservative measures for SB obstruction (n = 1), and loss to follow-up (n = 1). Patients with CE retention were more likely to have SB anastomoses (88% versus 23%) and partial obstruction (63% versus 38%) than patients with high-risk features for capsule retention who passed the capsule. CONCLUSIONS: In a tertiary care population without obstructive symptoms, capsule retention occurred in only 0.3% of cases. Review of surgical history and prior imaging for obstruction or SB anastomoses may help to reduce retention.

Clinical characteristics and imaging features of small bowel adenocarcinomas in Crohn's disease.

PURPOSE: Small bowel adenocarcinoma is uncommon in patients with Crohn's disease but has an extremely poor prognosis. There is a paucity of data on the clinical characteristics and radiologic features of this entity. We sought to update our institutional experience with small bowel adenocarcinoma occurring in the setting of Crohn's disease and to systematically re-examine pre-operative imaging findings. METHODS: Medical records were abstracted to identify all patients with Crohn's disease and small bowel adenocarcinoma who were evaluated at Mayo Clinic, Rochester, Minnesota and Mayo Clinic, Scottsdale, Arizona between 1976 and 2012. Clinical, demographic, and outcomes data were obtained for each patient. Pre-diagnosis radiologic imaging was re-evaluated by two gastrointestinal radiologists. RESULTS: Thirty-four patients (21 males) were identified. Median ages at Crohn's disease and cancer diagnoses were 22.4 and 52.9 years, respectively. Median follow-up after cancer diagnosis was 272.0 days; 22 patients (64.7%) had persistent or recurrent adenocarcinoma at last follow-up. 1- and 2-year mortality rates were 29.6% and 48.0%. Pre-operative imaging studies were available for re-review in 14 cases. Features concerning for malignancy included annular mass, nodularity at the extraluminal margins of the mass, and perforation. Nearly all tumors arose in regions of chronic inflammation and caused luminal narrowing with pre-stenotic dilatation. CONCLUSIONS: Small bowel adenocarcinoma is rare in patients with Crohn's disease but results in significant mortality. CT or MR imaging findings can be suggestive of the pre-operative diagnosis, but it is usually diagnosed at an advanced stage with laparotomy.

Validation of a CT-derived method for osteoporosis screening in IBD patients undergoing contrast-enhanced CT enterography.

OBJECTIVES: Osteoporosis and bone fractures are of particular concern in patients with inflammatory bowel disease (IBD). Biomechanical computed tomography (BCT) is an image-analysis technique that can measure bone strength and dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) from noncontrast CT images. This study seeks to determine whether this advanced technology can be applied to patients with IBD undergoing CT enterography (CTE) with IV contrast. METHODS: Patients with IBD who underwent a CTE and DXA scan between 2007 and 2011 were retrospectively identified. Femoral neck BMD (g/cm(2)) and T-scores were measured and compared between DXA and BCT analysis of the CTE images. Femoral strength (Newtons) was also determined from BCT analysis. RESULTS: DXA- and CTE-generated BMD T-score values were highly correlated (R(2)=0.84, P<0.0001) in this patient cohort (n=136). CTE identified patients with both osteoporosis (sensitivity, 85.7%; 95% confidence interval (CI), 48.7-97.4 and specificity, 98.5%; 95% CI, 94.5-99.6) and osteopenia (sensitivity, 85.1%; 95% CI, 72.3-92.6 and specificity, 85.4%; 95% CI, 76.6-91.3). Of the 16 patients who had "fragile" bone strength by BCT (placing them at the equivalent high risk of fracture as for osteoporosis), 6 had osteoporosis and 10 had osteopenia by DXA. CONCLUSIONS: CTE scans can provide hip BMD, T-scores, and clinical classifications that are comparable to those obtained from DXA; when combined with BCT analysis, CTE can identify a subset of patients with osteopenia who have clinically relevant fragile bone strength. This technique could markedly increase bone health assessments in IBD patients already undergoing CTE to evaluate small bowel disease.

Comparative outcomes of younger and older hospitalized patients with inflammatory bowel disease treated with corticosteroids.

BACKGROUND: Data on the differences in inpatient treatment approaches and outcomes between younger and older patients with inflammatory bowel disease (IBD) are limited. Therefore, we used a parallel cohort study design to compare outcomes between younger and older patients with IBD. METHODS: All anti-tumor necrosis factor (TNF)-naive patients aged 60 years and older hospitalized at our institution between 2003 and 2011 and treated with corticosteroids for an IBD flare were matched 1:1 to younger patients aged 18 to 50 years. Rates of corticosteroid response, colectomy, and initiation of anti-TNF therapy were compared. RESULTS: Sixty-five patients were identified in each cohort. Median ages were 70 years (range, 60-94) and 30 years (range, 18-50) for the older and younger groups, respectively. Twenty-three percent of older patients were refractory to corticosteroids compared with 38% of the younger cohort (odds ratio, 0.5; 95% confidence intervals, 0.2-1.1). Older corticosteroid-refractory patients had surgery (80% versus 72%) and were started on anti-TNF therapy (20% versus 12%; P = 0.71), at a similar frequency as younger patients. Older steroid-responsive patients were less likely to start an anti-TNF agent during the first year of follow-up than younger patients (7% versus 31%, P = 0.006), but there was no difference in 1-year colectomy rates (27% versus 28%, P = 0.63). CONCLUSIONS: Corticosteroid response was similar in older and younger patients hospitalized for IBD. Inpatient treatment for corticosteroid-refractory patients was similar between cohorts. Older corticosteroid-responsive patients were less likely to be treated with an anti-TNF than younger patients.

Tacrolimus salvage in anti-tumor necrosis factor antibody treatment-refractory Crohn's disease.

BACKGROUND: Several small retrospective studies have reported encouraging response rates in patients with Crohn's disease (CD) treated with tacrolimus. METHODS: We conducted a retrospective study of the use of oral tacrolimus for severe CD refractory to anti-tumor necrosis factor agents. Response was defined as a clinician's assessment of improvement after at least 7 days of treatment of one or more of the following: bowel movement frequency, fistula output, rectal bleeding, abdominal pain, extraintestinal manifestations, or well-being. Remission required all of the following: <3 stools per day, no bleeding, abdominal pain or extraintestinal manifestations, and increased well-being. RESULTS: Twenty-four eligible patients were treated with tacrolimus for a median of 4 months. Approximately 37% were steroid dependent or steroid refractory. Response and steroid-free remission rates were 67% and 21%, respectively, and lasted for a median of 4 months. Approximately 42% of patients were able to stop steroids and 54% of patients ultimately required surgery within a median of 10 months after starting tacrolimus. Patients with mean tacrolimus trough levels of 10 to 15 ng/mL had the highest rates of response (86%) and remission (57%). Surgery seemed to be postponed in this group compared with others. An adverse event occurred in 75% of patients. Eight of these events (33%) required dose reduction and 6 (25%) led to treatment discontinuation. There were no irreversible side effects or deaths attributable to tacrolimus over a median follow-up of 56 months. CONCLUSIONS: Oral tacrolimus seems to be safe and effective in some patients with severe CD refractory to anti-tumor necrosis factor therapy, particularly at a mean trough level of 10 to 15 ng/mL.

The experience of community-living men managing fecal incontinence.

PURPOSE: The purpose of this study was to investigate the lived experience of men managing fecal incontinence (FI). METHOD: A phenomenological method was used to investigate the experience of FI. Eleven men participated in unstructured interviews. Van Manen's approach was used for data analysis. RESULTS: The findings display men's experiences of living with FI through space, relationships, time and body. The essential theme generated from the analysis was "secret resignation." Resignation of having FI was the main coping strategy of the men in this study and was reflected in the limited approaches they used to manage their symptoms. The common reason of the resignation was considering FI normal for them and a consequence of aging. DISCUSSION AND CONCLUSION: The findings provide guidance to rehabilitation nurses to first inquire about the presence of FI, education men about its etiologies, and develop plans of care that address men's main concerns.

Endoscopic skipping of the distal terminal ileum in Crohn's disease can lead to negative results from ileocolonoscopy.

BACKGROUND & AIMS: Crohn's 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. METHODS: We analyzed data from 189 consecutive patients (55% women) with Crohn's 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 Crohn's disease activity. RESULTS: Of 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 Crohn's 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 Crohn's disease based on ileoscopy (41.1% for less than 5 years; P < .05). CTE detected extracolonic Crohn's 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). CONCLUSIONS: Ileoscopy examination can miss Crohn's 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 Crohn's disease.

Use of a screening tool to determine nonadherent behavior in inflammatory bowel disease.

OBJECTIVES: Nonadherence is an issue in the management of inflammatory bowel disease (IBD), and no validated screening tool is available. We aimed to determine whether scores from a self-reported adherence survey correlated with pharmacy refill data as a reliable measure of medication adherence. METHODS: We used the eight item, self-reported Morisky Medication Adherence Scale. Each question is worth a point, with a maximum score of 8. Pharmacies were contacted for refill information for the previous 3 months, then 3 and 6 months from enrollment. Refill data were recorded for each time interval as the medication possession ratio (MPR); adherence was defined as >80%. Analysis of variance was used to determine the relationship between survey scores and MPR by drug class. RESULTS: One hundred fifty outpatients were enrolled, of whom 94 had Crohn's disease and 56 had ulcerative colitis; 89 were female. At baseline, 47% of patients were on 5-aminosalicylic acid (5-ASA), 54% an immunomodulator, 15% infliximab, 8% an injectable biologic, and 6% budesonide. The median adherence score was 7. Fifty-two percent stated they "rarely" missed a dose of medication. The median adherence score, as defined by refill data, ranged from 0% (injectable biologic) to 75% (infliximab) by drug class. Only those on an immunomodulator had a survey score that positively correlated with adherence. CONCLUSIONS: Only those on a thiopurine were likely to have a score predicting adherence behavior. Adherence to therapy for IBD is complex and cannot be predicted reliably by a self-reported survey tool validated for other chronic conditions.

Similar outcomes of surgical and medical treatment of intra-abdominal abscesses in patients with Crohn's disease.

BACKGROUND & AIMS: It is not clear whether medical therapy, surgery, or both is the best approach for patients with Crohn's disease who develop an intra-abdominal abscess. METHODS: We evaluated data from patients with Crohn's 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. RESULTS: The 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). CONCLUSIONS: Among patients with Crohn's 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.

Enhancing adherence through education.

The treatment of multiple sclerosis (MS) has advanced greatly since the introduction of disease-modifying therapies (DMTs) in the early 1990s. Although the DMTs have exhibited significant efficacy in relapsing-remitting MS and other forms of the disease, the degree of benefit depends heavily on patient adherence to recommended regimens. This article addresses some of the most pressing areas of unmet need in educating advanced-practice nurses, neurologists, patients, and support care partners regarding strategies that can overcome obstacles to adherence. The observations presented here are based on clinical experience with real-life cognitive, psychosocial, and cultural impediments to adherence. The article also explores the ways in which adherence may be affected by emerging therapies for MS (such as oral agents) as well as the educational needs that will arise with the further evolution of MS care.

Monoclonal antibodies in MS: mechanisms of action.

The development of monoclonal antibodies (mAbs) presents an emerging, highly specific therapeutic strategy for the treatment of multiple sclerosis (MS). mAbs target selective molecules and have shown early promise, along with notable risks, in the treatment of MS and other immune-mediated diseases. The mechanism of action of the 4 mAbs under active investigation for MS (natalizumab, rituximab, alemtuzumab, and daclizumab) are reviewed, with a discussion of how mAb interaction with each target antigen may produce direct and indirect effects (proven and hypothesized) on immune cell activity, CNS-related inflammatory processes, and clinical outcomes.