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Pharmacodynamic assessment of vedolizumab for the treatment of ulcerative colitis.

ABSTRACT: Vedolizumab is an anti-integrin approved for the treatment of Crohn's disease and ulcerative colitis. By binding the ?4?7-integrin heterodimer, vedolizumab blocks leukocyte translocation into gastrointestinal tissue.This review discusses the chemistry, pharmacologic properties, clinical efficacy, and safety of vedolizumab in ulcerative colitis. Other medications available for the treatment of ulcerative colitis are also discussed.Vedolizumab is a promising new agent for the treatment of ulcerative colitis. Its mechanism of action differs from TNF-? inhibitors and immune suppressants, allowing it to be used in cases of TNF-? inhibitor failure or non-response, or as a first-line biologic drug. Available safety data suggests that vedolizumab is not associated with an increased risk of infection or malignancy; however, additional post-marketing data are required to confirm these initial reports. Vedolizumab is likely to be used in growing numbers of patients over the coming years.

SUBMITTER: McLean LP

PROVIDER: S-EPMC4917449 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Pharmacodynamic assessment of vedolizumab for the treatment of ulcerative colitis.

McLean Leon P LP Cross Raymond K RK

Expert opinion on drug metabolism & toxicology 20160512 7

<h4>Introduction</h4>Vedolizumab is an anti-integrin approved for the treatment of Crohn's disease and ulcerative colitis. By binding the α4β7-integrin heterodimer, vedolizumab blocks leukocyte translocation into gastrointestinal tissue.<h4>Areas covered</h4>This review discusses the chemistry, pharmacologic properties, clinical efficacy, and safety of vedolizumab in ulcerative colitis. Other medications available for the treatment of ulcerative colitis are also discussed.<h4>Expert opinion</h4> ...[more]

PMID: 27096357

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Project description:Background and objectivesUlcerative colitis is highly prevalent in Canada and cost-effective ulcerative colitis therapies are warranted. Vedolizumab subcutaneous (SC) formulation was recently approved for ulcerative colitis maintenance therapy. We assessed vedolizumab SC cost effectiveness vs conventional and advanced therapeutics in patients with moderately to severely active ulcerative colitis from a Canadian public healthcare payer perspective.MethodsA hybrid decision tree/Markov model was developed to evaluate vedolizumab SC costs, quality-adjusted life-years, and cost effectiveness vs conventional therapy, adalimumab SC, infliximab intravenous, golimumab SC, tofacitinib, ustekinumab SC, and vedolizumab intravenous. This model predicts the number of patients achieving clinical response and remission after treatment induction, and sustained benefit during maintenance treatment. To account for statistical uncertainties, the base-case analysis was conducted in a probabilistic manner. Scenario analyses examined the impact of previous treatment with anti-tumor necrosis factor agents, dose escalation, loss of efficacy, and treatment adherence.ResultsIn the base-case analysis, conventional therapy was the most cost-effective therapeutic option in the overall population. Vedolizumab SC was cost effective and dominant compared with other advanced therapies (adalimumab, golimumab, infliximab, tofacitinib 5 mg, ustekinumab, and vedolizumab intravenous). The annual vedolizumab SC cost per patient was reduced vs ustekinumab SC, tofacitinib 5 mg, vedolizumab intravenous, and golimumab SC by $47,024, $3251, $2120, and $2004 (Canadian dollars), respectively, and exceeded that of infliximab, adalimumab, and conventional therapy by $582, $3293, and $41,024, respectively. Among the treatments, vedolizumab SC generated the highest quality-adjusted life-years overall (14.21), which translated into the best incremental cost per quality-adjusted life-years gained over conventional therapy in the overall population ($109,374) and in anti-tumor necrosis factor-naïve and anti-tumor necrosis factor-experienced patients ($41,658/$114,287).ConclusionsConventional therapy offered the most cost-effective therapeutic option followed by vedolizumab SC. Based on a $50,000/quality-adjusted life-year threshold, vedolizumab was cost effective in anti-tumor necrosis factor-naïve patients but not the overall population also when compared to conventional therapy.

Project description:Background:Vedolizumab inhibits ?4?7-mediated lymphocyte trafficking and is effective in ulcerative colitis (UC). This study evaluated drug and biomarker concentrations and patient outcomes during vedolizumab treatment in UC. Methods:Prospectively scored maintenance clinical (26.5 weeks; interquartile range [IQR], 16.3-37.0 weeks) and endoscopic (23.5 weeks; IQR, 16.8-35.6 weeks) outcomes were compared with serum vedolizumab concentrations, antivedolizumab antibodies, and serum biomarkers at baseline and weeks 2, 6, 14, and 26. A linear mixed-effects model compared biomarker trajectories over time between clinical and endoscopic remitters and nonremitters. Results:Thirty-two patients were included. Soluble (s)-tumor necrosis factor (TNF)-?, s-?4?7, s-mucosal addressin cell adhesion molecule (s-MAdCAM-1), and s-amyloid A (s-AA) significantly changed with treatment. A linear mixed-effects model demonstrated that s-?4?7 (P = 0.044) increased and s-MAdCAM-1 (P = 0.006) and s-vascular cell adhesion molecule-1 (s-VCAM-1, P = 0.001) decreased more rapidly in patients achieving clinical remission in maintenance. S-MAdCAM-1 (P = 0.005), s-intracellular adhesion molecule-1 (ICAM-1; P = 0.014), s-VCAM-1 (P < 0.001), and s-TNF (P = 0.052) decreased more rapidly in endoscopic remitters. In clinical remitters, higher week 14 (20.3 ng/mL vs 6.0 ng/mL; P = 0.013) and week 26 (14.1 ng/mL vs 8.6 ng/mL; P = 0.05) s-?4?7 were observed. In endoscopic remitters, week 2 (6.7 pg/mL vs 17.8 pg/mL; P = 0.038) and week 6 (3.9 pg/mL vs 15.6 pg/mL; P = 0.005) s-TNF and week 14 s-VCAM (589.1 ng/mL vs 746.0 ng/mL; P = 0.05) were lower. Conclusion:Serum biomarkers were associated with outcomes in vedolizumab-treated UC patients. s-?4?7 increased, whereas s-MAdCAM-1, s-VCAM-1, s-ICAM-1, and s-TNF decreased more rapidly in remitters. At individual time points, induction s-TNF and maintenance s-VCAM-1 concentrations were lower, whereas maintenance s-?4?7 concentrations were higher in remitters.

Dataset Information

Pharmacodynamic assessment of vedolizumab for the treatment of ulcerative colitis.

Publications

Pharmacodynamic assessment of vedolizumab for the treatment of ulcerative colitis.

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