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Patients with moderate-to-severe ulcerative colitis were randomly assigned to receive placebo or induction doses of ustekinumab. Patients who had a response to induction therapy underwent a second randomization to maintenance therapy with ustekinumab or placebo. Ustekinumab was more effective than placebo for inducing and maintaining remission.

Mount Sinai Expert Guides: Gastroenterology will provide physicians with an extremely clinical and accessible handbook covering the major GI diseases and symptoms, their diagnosis and clinical management.   Perfect as a point-of-care resource on the hospital wards and also as a refresher for board exam preparation, the focus throughout is on providing rapid reference, essential information on each disease to allow for quick, easy browsing and assimilation of the must-know information.  All chapters follow a consistent template including the following features: - An opening bottom-line/key points section - Classification, pathogenesis and prevention of disease - Evidence-based diagnosis, including relevant algorithms, laboratory and imaging tests, and potential pitfalls when diagnosing a patient - Disease management including commonly used medications with dosages, when to perform surgery, management algorithms and how to prevent complications - How to manage special populations, ie, in pregnancy, children and the elderly - The very latest evidence-based results, major society guidelines (ASG/ACG/UEGW) and key external sources to consult In addition, the book comes with a companion website housing extra features such as case studies with related questions for self-assessment, key patient advice and ICD codes.  Each guide also has its own mobile app available for purchase, allowing you rapid access to the key features wherever you may be. If you specialise in gastroenterology and require a concise, practical guide to the clinical management of GI disease, bought to you by one of world's leading hospitals, then this is the perfect book for you. This title is also available as a mobile App from MedHand Mobile Libraries. Buy it now from iTunes [https://itunes.apple.com/us/app/mount-sinai-expert-guides/id981532548?ls=1&mt=8], Google Play [https://play.google.com/store/apps/details?id=com.medhand.WMTSG&hl=en] or the MedHand Store [https://www.medhand.com/products/mount-sinai-expert-guides-gastroenterology].

In this 52-week randomized trial, the α 4 β 7 integrin antibody vedolizumab was effective in treating ulcerative colitis. There were not significantly more adverse events with vedolizumab than with placebo, but the trial was not large or long enough to fully assess safety. Ulcerative colitis is a chronic inflammatory bowel disease characterized by symptoms of bloody diarrhea, abdominal cramps, and fatigue. 1 Current medical therapy has important limitations. Aminosalicylates 2 – 4 are only modestly effective; glucocorticoids can cause unacceptable adverse events and do not provide a benefit as maintenance therapy. Tumor necrosis factor (TNF) antagonists, although efficacious, 5 , 6 predispose patients to serious infection. 7 Thus, new treatment strategies are needed. The migration of leukocytes into inflamed intestinal tissue is highly regulated by specific molecular mechanisms. The α 4 β 7 integrin, 8 a cell-surface glycoprotein variably expressed on circulating B and T lymphocytes, interacts with mucosal addressin-cell . . .

In three phase 3 trials involving patients with ulcerative colitis, tofacitinib (an oral, small-molecule Janus kinase inhibitor) was more effective as induction and maintenance therapy than placebo. Infections were more common with tofacitinib. Ulcerative colitis is characterized by an increased frequency of bowel movements and bloody diarrhea, which has a negative effect on quality of life. 1 Current therapies for ulcerative colitis include mesalamine, glucocorticoids, thiopurines, and antagonists to tumor necrosis factor (TNF) and α4β7 integrin. 1 – 5 Many patients do not have a response to these therapies or have a response that is not sustained. Additional treatment options with new mechanisms of action are needed to increase efficacy rates. The Janus kinase (JAK) family comprises four intracellular tyrosine kinases — JAK1, JAK2, JAK3, and nonreceptor tyrosine-protein kinase 2 — that activate signal transducers and . . .

In this 52-week randomized trial, the α 4 β 7 integrin antibody vedolizumab was effective in treating Crohn's disease. The incidence of serious adverse events was higher with vedolizumab than with placebo. Crohn's disease is a chronic inflammatory bowel disease. 1 Current treatments include glucocorticoids, immunosuppressive agents (i.e., azathioprine, mercaptopurine, or methotrexate), and tumor necrosis factor (TNF) antagonists. 1 – 3 Many patients do not have a response to therapy, 4 and treatments are associated with important toxic effects. 5 , 6 Natalizumab, a monoclonal antibody that modulates gut and brain lymphocyte migration by antagonizing α 4 β 1 and α 4 β 7 integrin–mediated interactions, 7 is efficacious in the treatment of multiple sclerosis 8 , 9 and Crohn's disease. 10 – 12 Its use in patients with Crohn's disease has been limited by the development in some patients of progressive multifocal . . .

Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn’s disease and ulcerative colitis.IL-12 and IL-23 have been implicated in inflammatory bowel disease. In this Review, Vande Casteele and colleagues summarize the mechanistic role of IL-12 and IL-23 in inflammatory bowel disease, and discuss the clinical development of drugs targeting IL-12 and/or IL-23.

Vedolizumab is a gut-selective α4β7 integrin antagonist for the treatment of moderately to severely active Crohn's disease (CD). Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha (TNF-α) antagonist therapy (TNF-naïve) or who had discontinued TNF-α antagonist therapy because of inadequate response (i.e., primary nonresponse), loss of response, or intolerance (collectively classified as the TNF-failure population).MethodsPost hoc analyses of the efficacy data for 516 TNF-naïve and 960 TNF-failure patients from the GEMINI 2 and GEMINI 3 trials were evaluated at weeks 6, 10, and 52 and included clinical remission (CD Activity Index [CDAI] score ≤150), enhanced clinical response (≥100-point decrease from baseline in CDAI score), durable clinical remission (remission at ≥80% of visits), and corticosteroid-free remission. Adverse events were summarized for the TNF-naïve and TNF-failure subgroups by treatment received.ResultsAmong patients who responded to vedolizumab induction at week 6, 48.9% of TNF-naïve and 27.7% of TNF-failure patients were in remission with vedolizumab at week 52 (versus 26.8% and 12.8% with placebo). Clinical efficacy was similar between the different types of TNF-α antagonist failure or the number of prior TNF-α antagonists failed. Safety profiles were similar in both subpopulations.ConclusionsVedolizumab had increased efficacy over placebo in CD patients irrespective of TNF-α antagonist treatment history. Overall, rates of response and remission were numerically higher in patients receiving vedolizumab as a first biologic than in patients who had experienced TNF failure.

Crohn's disease and ulcerative colitis, collectively known as the inflammatory bowel diseases (IBD), are largely diseases of the twentieth century, and are associated with the rise of modern, Westernized industrial society. Although the causes of these diseases remain incompletely understood, the prevailing model is that the intestinal flora drives an unmitigated intestinal immune response and inflammation in the genetically susceptible host. A review of the past and present of these diseases shows that detailed description preceded more fundamental elucidation of the disease processes. Working out the details of disease pathogenesis, in turn, has yielded dividends in more focused and effective therapy for IBD. This article highlights the key descriptions of the past, and the pivotal findings of current studies in disease pathogenesis and its connection to medical therapy. Future directions in the IBD will likely explicate the inhomogeneous causes of these diseases, with implications for individualized therapy.

We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate-severe Crohn's disease (CD). 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. 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). 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.