Brenda D. Becker

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

BACKGROUND & AIMS Crohns 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 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. 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 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). CONCLUSIONS Ileoscopy 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.

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 Crohns disease who develop an intra-abdominal abscess. METHODS We 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. 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 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.

Natalizumab for moderate to severe Crohn's disease in clinical practice: The Mayo Clinic Rochester experience†

Background: Not all patients with Crohns disease (CD) respond or maintain response to anti‐tumor necrosis factor (TNF) agents and alternative treatment is necessary. Natalizumab, a monoclonal antibody to alpha‐4 integrin approved for CD, has demonstrated efficacy in randomized clinical trials. We describe our experience with natalizumab in clinical practice at Mayo Clinic Rochester. Methods: Consecutive patients prescribed natalizumab for active CD were invited to participate and were followed prospectively. Incidence of infection, hospitalization, neoplasm, or other adverse events were recorded. Clinical activity was assessed using the Harvey–Bradshaw Index at each 30‐day infusion visit. Results: Between April 2008 and September 2010, 36 patients were prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease duration was 9 years (range, 3–43). Twenty‐three patients had prior exposure to two anti‐TNF agents, seven to one agent. All patients experienced at least one adverse event; none of the 13 patients in whom natalizumab was stopped (43%) discontinued due to adverse events. Five patients had infusions held for infection. No patient developed progressive multifocal leukoencephalopathy (PML). Fourteen patients (46%) had clinical response. The cumulative probability of achieving complete response within 1 year was 56% (28%–73%). Four of seven patients were weaned off corticosteroids. Conclusions: In our experience with natalizumab in clinical practice, adverse events were manageable and did not result in treatment cessation. No PML cases were seen and clinical response was similar to that in clinical trials. Natalizumab results in clinical benefit in patients who have active disease and have failed anti‐TNF therapy (Inflamm Bowel Dis 2012;)

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.

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

OBJECTIVES:Crohns 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.

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/cm2) 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 (R2=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.

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.

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.

Efficacy and safety of certolizumab pegol for Crohn's disease in clinical practice

Certolizumab pegol (CZP) is Food and Drug Administration (FDA)‐approved to treat Crohns disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established.

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.