Development and Validation of a Digital Analysis Method to Quantify CD3-immunostained T Lymphocytes in Whole Slide Images of Crohn's Disease Biopsies.

The T-lymphocyte-mediated inflammation in Crohn's disease can be assessed by quantifying CD3-positive T-lymphocyte counts in colonic sections. We developed and validated a process to reliably quantify immunohistochemical marker-positive cells in a high-throughput setting using whole slide images (WSIs) of CD3-immunostained colonic and ileal tissue sections. In regions of interest (ROIs) and/or whole tissue sections of 40 WSIs from 36 patients with Crohn's disease, CD3-positive cells were quantified by an expert gastrointestinal pathologist (gold standard) and by image analysis algorithms developed with software from 3 independent vendors.

Vedolizumab and Extraintestinal Manifestations in Inflammatory Bowel Disease.

In Crohn's disease and ulcerative colitis, inflammation is not limited to the digestive tract. Extraintestinal manifestations (EIMs), which affect up to 50% of patients, can substantially impair quality of life. EIMs may parallel luminal disease activity or have an independent course.

Biomarkers of Crohn's Disease to Support the Development of New Therapeutic Interventions.

Background: Currently, 2 coprimary end points are used by health authorities to determine the effectiveness of therapeutic interventions in patients with Crohn's disease (CD): symptomatic remission (patient-reported outcome assessment) and endoscopic remission (ileocolonoscopy). However, there is lack of accepted biomarkers to facilitate regulatory decision-making in the development of novel therapeutics for the treatment of CD.

Methods: With support from the Helmsley Charitable Trust, Critical Path Institute formed the Crohn's Disease Biomarkers preconsortium (CDBpC) with members from the pharmaceutical industry, academia, and nonprofit organizations to evaluate the CD biomarker landscape.

How Will Evolving Future Therapies and Strategies Change How We Position the Use of Biologics in Moderate to Severely Active Inflammatory Bowel Disease.

Several biological agents have been added to our armamentarium of treatment options for moderate to severely active inflammatory bowel diseases, and this number is expected to only increase in the near future. With our growing understanding of disease mechanisms and pharmacokinetics, we are now able to target several mechanisms of action to achieve key endpoints (steroid-free remission and mucosal healing) associated with improved long-term disease-related outcomes. In this context, concerns arise regarding the optimal positioning of currently available biologics and key biologics in development.