Vedolizumab for the Treatment of Moderately to Severely Active Ulcerative Colitis

Abstract

Ulcerative colitis is a chronic, idiopathic, inflammatory bowel disease characterized by a relapsing and remitting course. A substantial proportion of patients fail conventional therapies despite therapy with immunosuppressives and tumor necrosis factor antagonists. Accordingly, newer therapeutic agents that target disease-specific inflammation and minimize adverse events are required. Central to the pathogenesis of ulcerative colitis is an aberrant host response to commensal microorganisms with a resultant dysregulation of gut immune homeostasis and lymphocyte trafficking. Recently, a newer biologic, vedolizumab, which blocks lymphocyte trafficking, has been developed for use in moderate to severe ulcerative colitis. The efficacy of this agent has been demonstrated to be similar to that of other currently available biologics, and the selectivity of this agent in blocking lymphocyte migration to the gut has substantially reduced treatment-related adverse events. The drug has now been approved for use in the United States and Europe, and, although the exact positioning of this biologic in clinical practice is yet to be defined, it represents an important new chapter in our armamentarium of treatment options for this population. In this review, we will highlight key considerations to be made by providers when using this agent in clinical practice.

A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab

“…The European prescribing information suggests that some patients with UC or CD who have experienced a decrease in their response to vedolizumab may benefit from an increase in dosing frequency to every 4 weeks [ 8 ]. The clinical profile of vedolizumab is consistent with its binding specificity, with evidence of therapeutic benefit in patients with UC or CD [ 9 – 13 ] and a lack of systemic immunosuppression [ 14 , 15 ]. The aim of this article is to review the clinical pharmacokinetics, pharmacodynamics, exposure–efficacy relationships, and immunogenicity of vedolizumab.…”

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

“…Vedolizumab may be an appropriate alternative in certain populations where the enhanced safety profile may be beneficial. 105 The exact positioning of adalimumab within current treatment algorithms remains unclear. It has been suggested that the reduced efficacy as compared to infliximab is a result of under dosing, and clinical trials are currently underway to address this question through a high dose induction regimen.…”

Comparative Effectiveness of Second-Line Biological Therapies for Ulcerative Colitis and Crohn’s Disease in Patients With Prior Failure of Anti-Tumour Necrosis Factor Treatment

“…It inhibits integrin α4β7, a cell-surface glycoprotein variably expressed on circulating B and T lymphocytes, thus inhibiting lymphocyte tra cking from the blood vessels to the intestines. [9] Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit of interleukin (IL)-12 and IL-23. [10] Tofacitinib, an oral medication, is a selective small-molecule Janus kinase (JAK) inhibitor that preferentially inhibits JAK 1 and JAK 3.…”