Faculty Bibliography

OBJECTIVES: We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate-severe Crohn's disease (CD). METHODS: Retrospective cohort study of seven medical centers, from May 2014 to December 2015. Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included. Using the multivariable Cox proportional hazard analyses, we identified independent predictors of clinical remission or mucosal healing with VDZ. Rates of serious infection (requiring antibiotics, resulting in discontinuation of VDZ, hospitalization or death) and serious adverse events (discontinuation of VDZ, hospitalization or death) were described quantitatively. RESULTS: We included 212 patients with moderate-severe CD (median age 34 years; 40% male; 90% tumor necrosis factor (TNF)-antagonist exposed) with a median follow-up (IQR) of 39 weeks (25-53). Twelve-month cumulative rates of clinical remission, mucosal healing, and deep remission (clinical remission+mucosal healing) were 35%, 63%, and 26%, respectively. Individuals with prior TNF-antagonist exposure (hazard ratio (HR) 0.40; 95% confidence interval (CI): 0.20-0.81), smoking history (HR 0.47; 95% CI: 0.25-0.89), active perianal disease (HR 0.49; 95% CI: 0.27-0.88), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve clinical remission. Those with prior TNF-antagonist exposure (HR 0.29; 95% CI: 0.12-0.73), and severe disease activity (HR 0.54; 95% CI: 0.31-0.95) were less likely to achieve mucosal healing. During 160 patient years of follow-up (PYF) and 1,433 VDZ infusions, 5 patients developed infusion reactions (3.5 per 1,000 infusions), 21 developed serious infections (13 per 100 PYF), and 17 developed serious adverse events (10 per 100 PYF). A minority of adverse events required discontinuation of therapy (6 per 100 PYF). CONCLUSIONS: VDZ is a safe and effective treatment option for moderate-severe CD in routine practice. Clinical remission and deep remission (clinical remission and mucosal healing) can be achieved in 1/3 of individuals, and a minority of individuals require discontinuation of therapy due to adverse events.

The optimal method for monitoring quiescent disease in patients with Crohn's disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD.

Crohn's disease (CD) is a complex, immune-mediated disorder that often requires a multi-modality approach for optimal diagnosis and management. While traditional methods include ileocolonoscopy and radiologic modalities, increasingly, capsule endoscopy (CE) has been incorporated into the algorithm for both the diagnosis and monitoring of CD. Multiple studies have examined the utility of this emerging technology in the management of CD, and have compared it to other available modalities. CE offers a noninvasive approach to evaluate areas of the small bowel that are difficult to reach with traditional endoscopy. Furthermore, CE maybe favored in specific sub segments of patients with inflammatory bowel disease (IBD), such as those with IBD unclassified (IBD-U), pediatric patients and patients with CD who have previously undergone surgery.

With the increased use of anti-TNF therapy for both ulcerative colitis and Crohn's disease, there is serious concern about long term adverse events, especially malignancy. Recent data suggests that anti-TNF agents increase the risk of non-Hodgkin's lymphoma; however, there is limited evidence on the risk of solid tumors. Many patients have been exposed to other immunosuppressive therapies in the past making it difficult to discern the true risk of malignancy with TNF-alpha inhibitors alone. The purpose of this review is to discuss the risk of extra-intestinal solid cancer, excluding skin cancer, in adult inflammatory bowel disease patients exposed to anti-TNF agents.