Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study).

OBJECTIVE: Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. DESIGN: Patients 50 to 75 years of age (African Americans, 45-75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. RESULTS: From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. CONCLUSION: CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov no: NCT02754661.

Panenteric capsule endoscopy versus ileocolonoscopy plus magnetic resonance enterography in Crohn's disease: a multicentre, prospective study.

INTRODUCTION: Crohn's disease diagnosis and monitoring remains a great clinical challenge and often requires multiple testing modalities. Assessing Crohn's disease activity in the entire gastrointestinal (GI) tract using a panenteric capsule endoscopy (CE) system could be used as an alternative to colonoscopy and cross-sectional imaging. This study assessed the accuracy and safety of panenteric CE in Crohn's disease as compared with ileocolonoscopy (IC) and/or magnetic resonance enterography (MRE). METHODS: A prospective, multicentre study was performed in subjects with established Crohn's disease. Individuals with proven small bowel patency underwent a standardised bowel preparation, followed by CE ingestion and IC either the same or following day. MRE, IC, and CE interpretations were performed by blinded central readers using validated scoring systems. The primary endpoint was the overall sensitivity of CE vs MRE and/or IC in Crohn's disease subjects. RESULTS: Study enrolment included 158 subjects from 21 sites in the USA, Austria, and Israel. Of those, 99 were included in the analysis. Imaging modality scores indicated none to mild inflammation in the proximal small bowel and colon, but discrepant levels of inflammation in the terminal ileum. Overall sensitivity for active enteric inflammation (CE vs MRE and/or IC) was 94% vs 100% (p=0.125) and specificity was 74% vs 22% (p=0.001). Sensitivity of CE was superior to MRE for enteric inflammation in the proximal small bowel (97% vs 71%, p=0.021), and similar to MRE and/or IC in the terminal ileum and colon (p=0.500-0.625). There were seven serious adverse advents of which three were related to the CE device. CONCLUSION: Panenteric CE is a reliable tool for assessing Crohn's disease mucosal activity and extent compared with more invasive methods. This study demonstrates high performance of the panenteric CE as compared to MRE and/or IC without the need for multiple tests in non-stricturing Crohn's disease. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03241368.

Utility of video capsule endoscopy for longitudinal monitoring of Crohn's disease activity in the small bowel: a prospective study.

BACKGROUND AND AIMS: This prospective, multicenter study evaluated small-bowel capsule endoscopy (CE) for the longitudinal assessment of mucosal inflammation in subjects with Crohn's disease (CD). METHODS: Subjects with known CD underwent clinical evaluation with ileocolonoscopy and CE at baseline and 6-month follow-up. Small-bowel patency was confirmed before CE at both time points. The Simple Endoscopic Score for CD (SES-CD) was used for ileocolonoscopy, and the Lewis score and the CE CD Endoscopic Index of Severity (CECDEIS) were used for CE. Clinical scoring indices included the Physician Global Assessment (PGA), CD Activity Index (CDAI), and Harvey-Bradshaw Index (HBI). Laboratory markers including C-reactive protein, fecal calprotectin, and erythrocyte sedimentation rate were collected at baseline and follow-up. Correlation between endoscopic scores and clinical parameters were measured using Spearman tests. RESULTS: A total of 74 subjects were enrolled, of whom 53 (72%) completed endoscopic procedures at baseline and 6-month follow-up. The SES-CD ileocolonoscopy score correlated with the Lewis score (P < .001, ρ = .59) and CECDEIS capsule score (P = .002, ρ = .48). None of the 3 endoscopic scores correlated with PGA, CDAI, HBI, C-reactive protein, erythrocyte sedimentation rate, or fecal calprotectin. Approximately 85% of subjects had proximal small-bowel inflammation identified on CE. There were no CE-related adverse events. CONCLUSIONS: There was high correlation between CE and ileocolonoscopy scores for the assessment of mucosal disease activity over time; however, there were no correlations between endoscopic scores and clinical parameters. The use of serial CE for the assessment of small-bowel CD is feasible and valid. (Clinical trial registration number: NCT01942720.).

Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND: Approximately 15-20% of ulcerative colitis patients and 20-40% of those with Crohn's disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. AIMS: This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. METHODS: We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. RESULTS: Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn's disease. CONCLUSIONS: These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease.

BACKGROUND & AIMS: Interleukin-12 and interleukin-23 are inflammatory cytokines implicated in Crohn's disease pathophysiology. Ustekinumab is a monoclonal antibody against the p40 subunit of interleukin-12/23. METHODS: We performed a double-blind, cross-over trial of the clinical effects of ustekinumab in 104 patients with moderate-to-severe Crohn's disease (population 1). Patients were given subcutaneous placebo at weeks 0-3, then ustekinumab at weeks 8-11; subcutaneous ustekinumab at weeks 0-3, then placebo at weeks 8-11; intravenous placebo at week 0, then ustekinumab at week 8; or intravenous ustekinumab at week 0, then placebo at week 8. Furthermore, an open-label trial evaluated the effects of 4 weekly subcutaneous injections or 1 intravenous infusion of ustekinumab in 27 patients who were primary or secondary nonresponders to infliximab (population 2). RESULTS: In population 1, clinical response rates for the combined groups given ustekinumab and placebo were 53% and 30% (P = .02), respectively at weeks 4 and 6, and 49% and 40% (P = .34), respectively at week 8. In a subgroup of 49 patients who were previously given infliximab (neither primary nor secondary nonresponders), clinical response to ustekinumab was significantly greater than the group given placebo (P < .05) through week 8. In population 2, the clinical responses at week 8 to subcutaneous and intravenous ustekinumab were 43% and 54%, respectively. There was no increase in the number of adverse or serious adverse events in patients given ustekinumab through week 8 compared with placebo. CONCLUSIONS: Ustekinumab induced a clinical response in patients with moderate-to-severe Crohn's disease, especially in patients previously given infliximab.

Cumulative experience with short- and long-term toxicity to 6-mercaptopurine in the treatment of Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: The efficacy of 6-mercaptopurine (6-MP) in the treatment and long-term maintenance of remission of inflammatory bowel disease and prevention of recurrence after resection in Crohn's disease have been established. Concern about 6-MP toxicity remains, especially the development of neoplasm. The aim of this study is to determine the incidence of all short- and long-term toxicity by follow-up of all patients with inflammatory bowel disease treated with 6-MP over a 20-year period. MATERIALS AND METHODS: We reviewed the office and hospital records and also determined the recent status of 410 patients with inflammatory bowel disease treated with 6-MP from 1980 to 1999. All toxicity was recorded. RESULTS: There was a low incidence of early drug-related allergic reactions (3.9%) and pancreatitis (1.2%). Desensitization to either 6-MP or azathioprine is often successful with the same or the other drug. Significant leukopenia (

Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease.

OBJECTIVES: Pyoderma gangrenosum is an immune-mediated inflammatory condition characterized by ulcerative skin lesions affecting 1-2% of patients with inflammatory bowel disease (IBD). Treatment includes wound care, antibiotics, corticosteroids, and immunomodulators. However, response to therapy varies, and many patients with pyoderma gangrenosum have disease that is refractory to these agents. The aim of this study was to assess the response of medically refractory pyoderma gangrenosum to infliximab. METHODS: This was a multicenter retrospective study of patients with IBD and medically refractory pyoderma gangrenosum treated with infliximab. Data collected included the following: baseline demographics; duration of IBD; history of bowel resection; duration of skin lesions; number, size, and location of pyoderma gangrenosum lesions; prior medications; dose and number of infliximab infusions; bowel activity before and after infliximab; pyoderma gangrenosum activity before and after infliximab therapy; time to response and time to healing of pyoderma gangrenosum lesions; recurrence of pyoderma gangrenosum after infliximab; corticosteroid taper; and adverse reactions to infliximab. RESULTS: There were 13 patients with moderate to severe pyoderma gangrenosum and IBD treated with infliximab. All patients demonstrated complete healing of the skin lesions. Three patients had a complete response to induction infliximab therapy and did not require additional treatment. Ten patients responded to induction infliximab and have maintained pyoderma gangrenosum healing with infusions every 4-12 wk. All patients receiving corticosteroids were able to discontinue them completely after institution of infliximab treatment. Infliximab was well tolerated; the only treatment-related adverse events were sunburn in one patient and an infusion reaction in another. CONCLUSIONS: Infliximab is a safe and effective treatment for IBD-associated pyoderma gangrenosum.