A review of vedolizumab and ustekinumab for the treatment of inflammatory bowel diseases.
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ABSTRACT:
SUBMITTER: Shim HH
PROVIDER: S-EPMC6207060 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
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A review of vedolizumab and ustekinumab for the treatment of inflammatory bowel diseases.
Shim Hang Hock HH Chan Pak Wo PW Chuah Sai Wei SW Schwender Brian J BJ Kong San Choon SC Ling Khoon Lin KL
JGH open : an open access journal of gastroenterology and hepatology 20180620 5
Recent advancement in the understanding of the pathophysiology of inflammatory bowel disease has seen an expansion in therapeutic options. Vedolizumab, a selective α4β7 inhibitor, and ustekinumab, an IL 12/23 p40 inhibitor, have provided the much-awaited out-of-class alternatives for patients who have failed or who are intolerant to anti-Tumor Necrosis Factor (TNF) therapy. However, questions remain as to how we may best use these novel therapeutic agents. We evaluate the evidence available from ...[more]
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Project description:The goal of therapeutic drug monitoring (TDM) is to optimize anti-TNF (tumor necrosis factor) biologic treatment in patients with inflammatory bowel disease (IBD). Although commercial assays are readily available for both ustekinumab and vedolizumab, the use of TDM with these newer biologic medications is at its infancy. The clinical utility of TDM with non-anti-TNF mechanisms of action is not clear. This review summarizes the latest available data on the pharmacokinetics of newer biologic and oral small molecules and highlights the threshold concentrations that have been associated with improved outcomes in IBD patients.
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Project description:Background & aimsThere are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice.MethodsWe performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs.ResultsOur analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections.ConclusionIn a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.
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Project description:Inflammatory bowel disease (IBD) is the chronic inflammatory disorder of gastrointestinal tract consisting of two subtypes: Ulcerative colitis and Crohn's disease. IBD occurs due to infiltration of leukocytes in intestinal mucosa and derangements in intestinal barrier function. One of the most important steps in pathogenesis of IBD is the interactions between integrins on the surface of leukocyte. The ?4?7 integrin expressing T-cell is an important leukocyte involved in pathogenesis and represents a new drug target for the treatment of IBD. Vedolizumab is a humanized monoclonal antibody, which acts against ?4?7 integrin heterodimer and blocks the interaction of ?4?7 integrin with MAdCAM-1. It prevents leukocyte binding to endothelial surface and its extravasation into affected tissue. The efficacy and safety of the vedolizumab have been established in many clinical studies. It has shown promising results in various clinical studies where a greater percentage of patients as compared to a placebo achieved and maintained clinical response, clinical remission, and corticosteroid-free clinical remission. Vedolizumab has been shown to be well tolerated with slightly higher risk of infections, headache, naspharyngitis as compared to placebo. This review focuses on the potential role of vedolizumab for the treatment of IBD.
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