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.

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 Crohn's 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.

Adalimumab for Crohn's disease in clinical practice at Mayo clinic: the first 118 patients.

BACKGROUND: We sought to assess the effectiveness and safety of adalimumab for the treatment of Crohn's disease (CD) in clinical practice. METHODS: Demographic, clinical, and treatment data were abstracted from the medical record. The primary outcome was clinical response to induction therapy with adalimumab for CD (complete, partial, or nonresponse). RESULTS: In all, 118 patients were prescribed adalimumab for CD between January 2003 and June 2007. All but five subjects (96%) had received prior infliximab and 50 were on systemic corticosteroids at the time of initial adalimumab dose (44%). A complete response was achieved in 53 patients and 20 patients had no response. The cumulative probability of any response (complete or partial) was 81.3% at 1 year. Dose escalation was required in 59 patients (1-year cumulative probability, 54.0%). Among patients with complete response, 18 lost response during follow-up (1-year cumulative probability, 21.4%). Among 50 patients on corticosteroids at baseline the median daily dose was 20 mg, which decreased to a median of 0 mg during treatment. Sixty-four patients (54%) experienced a total of 117 adverse events. Thirteen patients (11%) experienced 15 serious adverse events. Sixteen patients (14%) discontinued adalimumab due to an adverse event. CONCLUSIONS: Adalimumab was both effective and well tolerated for the treatment of CD in this tertiary practice with a high prevalence of past infliximab exposure. This experience largely predates FDA approval of adalimumab for CD.

Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease.

OBJECTIVES: Human anti-chimeric antibodies (HACAs) and subtherapeutic infliximab concentrations are associated with decreased duration of response. We evaluated the clinical utility of measuring HACA and infliximab concentrations. METHODS: The medical records of patients with inflammatory bowel disease (IBD) who had HACA and infliximab concentrations measured were reviewed to determine whether the result affected clinical management. RESULTS: One hundred fifty-five patients had HACA and infliximab concentrations measured. The main indications for testing were loss of response to infliximab (49%), partial response after initiation of infliximab (22%), and possible autoimmune/delayed hypersensitivity reaction (10%). HACAs were identified in 35 patients (23%) and therapeutic infliximab concentrations in 51 patients (33%). Of 177 tests assessed, the results impacted treatment decisions in 73%. In HACA-positive patients, change to another anti-tumor necrosis factor (TNF) agent was associated with a complete or partial response in 92% of patients, whereas dose escalation had a response of 17%. In patients with subtherapeutic infliximab concentrations, dose escalation was associated with complete or partial clinical response in 86% of patients whereas changing to another anti-TNF agent had a response of 33%. Patients with clinical symptoms and therapeutic infliximab concentrations were continued at the same dose 76% of the time and had no evidence of active inflammation by endoscopic/radiographic assessment 62% of the time. CONCLUSIONS: Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.

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.

Clinical features and outcome of patients with inflammatory bowel disease who use narcotics: a case-control study.

BACKGROUND: The role of narcotic use in patients with inflammatory bowel disease (IBD) is poorly defined. We sought to determine the clinical features of patients with IBD who use narcotics and factors associated with the discontinuation of narcotics. METHODS: A centralized index was used to identify 100 cases (patients with IBD receiving narcotics) and 100 matched controls evaluated in an IBD clinic between 1999 and 2002. Associations of clinical factors with case or control status were summarized as overall percentages and assessed using conditional logistic regression. Associations within cases were assessed using Fisher's exact test. RESULTS: Review of 361 charts identified 100 patients with IBD receiving narcotics (cases). One hundred matched controls were then identified. Cases were significantly associated with: female gender (64% cases versus 45% controls, P = 0.01), >or=2 IBD-related surgeries (42% versus 17%, P < 0.001), moderate-to-severe pain (93% versus 20%, P < 0.001), and moderate-to-severe symptoms (83% versus 33%, P < 0.001). Significant associations were detected for depression (42% versus 19%, P < 0.001), anxiety (19% versus 7%, P = 0.02), history of abuse (sexual, emotional, or physical, 17% versus 3%, P = 0.006), and for substance abuse (excluding alcohol) (14% versus 1%, P = 0.01). Of 39 cases that returned for follow-up, 22 (56%) had discontinued narcotics. Discontinuing narcotics was associated with medical treatment adherence (100% versus 53%), none-to-mild pain (73% versus 18%), and none-to-mild clinical activity (80% versus 24%). CONCLUSIONS: Narcotic use in IBD patients is associated with female gender, >or=2 previous surgeries, moderate to severe pain, and clinical disease activity, depression, anxiety, sexual, emotional and physical abuse, and substance abuse.

Small-bowel imaging in Crohn's disease: a prospective, blinded, 4-way comparison trial.

BACKGROUND: With the introduction of new techniques to image the small bowel, there remains uncertainty about their role for diagnosing Crohn's disease. OBJECTIVE: To assess the sensitivity and specificity of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy, and small-bowel follow-through (SBFT) in the diagnosis of small bowel Crohn's disease. METHODS: Prospective, blinded trial. SETTING: Inflammatory bowel disease clinic at an academic medical center. PATIENTS: Known or suspected Crohn's disease. Exclusion criteria included known abdominal abscess and non-steroidal anti-inflammatory drug (NSAID) use. Partial small-bowel obstruction (PSBO) at CTE excluded patients from subsequent CE. INTERVENTIONS: Patients underwent all 4 tests over a 4-day period. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, and accuracy of each test to detect active small-bowel Crohn's disease. The criterion standard was a consensus diagnosis based upon clinical presentation and all 4 studies. RESULTS: Forty-one CTE examinations were performed. Seven patients (17%) had an asymptomatic PSBO. Forty patients underwent colonoscopy, 38 had SBFT studies, and 28 had CE examinations. Small-bowel Crohn's disease was active in 51%, absent in 42%, inactive in 5%, and suspicious in 2% of patients. The sensitivity of CE for detecting active small-bowel Crohn's disease was 83%, not significantly higher than CTE (83%), ileocolonoscopy (74%), or SBFT (65%). However, the specificity of CE (53%) was significantly lower than the other tests (P < .05). One patient developed a transient PSBO due to CE, but no patients had retained capsules. LIMITATION: Use of a consensus clinical diagnosis as the criterion standard-but this is how Crohn's disease is diagnosed in practice. CONCLUSIONS: The sensitivity of CE for active small-bowel Crohn's disease was not significantly different from CTE, ileocolonoscopy, or SBFT. However, lower specificity and the need for preceding small-bowel radiography (due to the high frequency of asymptomatic PSBO) may limit the utility of CE as a first-line test for Crohn's disease.

Budesonide in the treatment of inflammatory bowel disease: the first year of experience in clinical practice.

BACKGROUND: Delayed release budesonide was approved by the FDA for the treatment of mildly to moderately active Crohn's disease involving the ileum and ascending colon. Controlled trials have demonstrated that budesonide is effective in inducing remission and for maintenance of remission, with less frequent steroid side effects than conventional steroids. We sought to determine the benefit of this medication in clinical practice and to identify any non-FDA-approved uses that may warrant further study. METHODS: Patients in whom oral budesonide was prescribed between November 1, 2001 and October 31, 2002, were identified and medical records were reviewed. Patients were categorized by indication for therapy: ileocolonic Crohn's disease (group 1), Crohn's disease elsewhere (group 2), and other conditions (group 3). RESULTS: A total of 225 patients were identified (108 in group 1, 62 in group 2, and 55 in group 3). Group 3 included patients with microscopic colitis (n = 28), pouchitis (n = 13), ulcerative colitis (n = 12), and celiac disease (n = 2). A favorable outcome occurred in 61% of group 1 patients but only 24% of patients in group 2. In group 3, only microscopic colitis patients and pouchitis patients experienced response rates >50% (77% and 60%, respectively). CONCLUSION: Budesonide is effective in a majority of patients with ileocolonic Crohn's disease and microscopic colitis, which is consistent with results reported from clinical trials. A majority of patients with pouchitis also benefit from budesonide therapy, but prospective controlled trials are necessary to clarify the benefit in this group.

Laboratory studies in the evaluation of urologic disease: Part I.

This is the first of a two-part article reviewing basic laboratory, imaging, endoscopic, urodynamic, and miscellaneous studies used for screening and diagnosis of urologic disease. Normal values, recommended collection procedures, and interpretation of results are also reviewed. This initial installment deals with laboratory tests used in urologic disease.

Diagnostic tests and tools in the evaluation of urologic disease: Part II.

This is the second of a two-part article reviewing basic laboratory, imaging, endoscopic, urodynamic, and miscellaneous studies used for screening and diagnosis of urologic disease. Part one dealt with laboratory analysis. This installment deals with diagnostic tests and tools used in urologic disease.