Immune-mediated colitis associated with ocrelizumab: A new safety risk.

BACKGROUND: An association between certain immunomodulatory therapies (rituximab, ipilimumab, and other immune checkpoint inhibitors) and inflammatory (non-ischemic and non-infectious) colitis in oncologic and non-oncologic patient populations is well documented in the medical literature. OBJECTIVE: The purpose of this case series is to describe adverse event reports of new onset, inflammatory colitis in association with ocrelizumab in patients with multiple sclerosis submitted to U.S. Food and Drug Administration (FDA) or published in the medical literature. METHODS: The FDA Adverse Event Reporting System (FAERS) and medical literature were searched. RESULTS: A review of postmarketing cases from FAERS and published medical literature identified 38 cases consistent with inflammatory, non-ischemic, and non-infectious colitis in association with ocrelizumab. The median time-to-onset was 8 months. Cases were reported using the following diagnostic terms: Crohn's disease (13), unspecified colitis (11), microscopic colitis (5), ulcerative colitis (5), medication-induced colitis (3), and autoimmune colitis (2). CONCLUSIONS: This case series highlights ocrelizumab induced immune-mediated colitis that can be clinically severe and potentially life-threatening. Based on the findings of this review, the ocrelizumab Prescribing Information was amended to include immune-mediated colitis in the Warnings and Precautions section.

Antitumor Necrosis Factor-α Therapy Is Associated With Reduced Risk of Thromboembolic Events in Hospitalized Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thromboembolic events. The aim of this study was to assess whether treatment with anti-tumor necrosis factor-α (TNF-α) therapy was associated with a decreased risk of thromboembolism. METHODS: We identified IBD patients hospitalized between July 2002 and July 2011 at our institution. Demographic data, medications, indication for hospitalization, and type of thromboembolic event were obtained by chart review. Wald tests were used to calculate an association between clinical characteristics and risk of thromboembolism. A multivariable logistic regression model was used to identify independent risk factors for thromboembolic events. RESULTS: A total of 547 patients (1048 hospitalizations) were identified. Fifty thromboembolic events occurred. Patient-related factors associated with thromboembolism included older age (P<0.0001), chronic kidney disease (P=0.001), diabetes (P=0.009), liver disease (P=0.005), and prior history of thromboembolism (P<0.0001). Acute infection (P=0.009), trauma (P=0.009), prolonged hospitalization (P<0.0001), and lack of thromboembolic prophylaxis (P<0.0001) were also associated with increased risk. Systemic corticosteroids were associated with increased risk of thromboembolism (P=0.003), whereas TNF-α inhibitors were protective (P=0.011). Multivariate regression identified systemic corticosteroid use (OR=4.62, P=0.0004) as associated with an increased risk of thromboembolism. TNF-α inhibitors were associated with a reduced risk of thromboembolism (OR=0.20, P=0.049). CONCLUSIONS: In this cohort of hospitalized IBD patients, TNF-α inhibitor therapy was associated with a reduced risk of thromboembolism, whereas systemic corticosteroid use was associated with an increased risk of thromboembolism.

Gut sensing mechanisms.

The mechanisms by which the gut senses and responds to nutrients involve the interplay of multiple complex pathways. In addition to regulating digestion and absorption, the pathways stimulated by molecules in the gut lumen mediate gastric motility, food intake, and satiety. Furthermore, protective mechanisms are activated as necessary to prevent injury, promote healing, and limit intake and absorption of potentially toxic substances. This review provides an update on the current knowledge and recent findings related to gastric sensing of nutrients, highlighting recent research and future endeavors in the field.