Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Singh, Siddharth; Dulai, Parambir S.; Casteele, Niels Vande; Battat, Robert; Fuméry, Mathurin; Boland, Brigid S.; Sandborn, William J.

doi:10.1111/apt.15484

Cited by 46 publications

(42 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple studies in patients with active CD have shown a correlation between VDZ exposure and response, and higher clinical and endoscopic remission rates when stratified by drug exposure. [4][5][6][7][8][9][10] These findings hold out the possibility that dose intensification in patients with low VDZ trough concentrations during induction may result in higher remission rates. In support of this notion, observational data suggest that empiric administration of an additional drug dose in patients with suboptimal response to induction may improve outcomes.…”

Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 73%

See 1 more Smart Citation

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

Dulai

Amiot²,

Peyrin–Biroulet³

et al. 2019

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

Background:A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease.Aim: To assess the utility of this CDST for predicting exposure-efficacy and disease outcomes.Methods: Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST-defined response groups (low, intermediate and high). Results:A linear relationship existed between CDST-defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST-defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high-probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the highintermediate and low-probability groups within GETAID were no longer significant when including low-probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low-to intermediate-probability vs high-probability patients (adjusted HR 2.06, 95% CI 1.33-3.21). Conclusions:We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure-efficacy relationships and rapidity of onset of action and could be used to help identify patients who would mostThis is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AA has received consulting fees from AbbVie, Hospira, Takeda, Gilead and Biocodex, as well as lecture fees and travel accommodations from AbbVie, Janssen, Biocodex, Hospira, Ferring, Takeda and MSD. AA has also received advisory board fees from Gilead, Takeda and AbbVie. LPB has received consulting fees from Merck,

show abstract

Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 73%

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

Dulai

Amiot²,

Peyrin–Biroulet³

et al. 2019

Aliment Pharmacol Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…The probability of clinical remission in both CD and UC patients increased to higher C min values (95%CI, 35–84 mg/L) achieved at week 6 ( Rosario et al, 2017 ). A more recent meta-analysis found a significant association between vedolizumab trough concentrations (>20 and >12 mg/L at week six and at maintenance, respectively) and therapeutic outcomes in UC patients but not in CD individuals ( Singh et al, 2019 ). Of note, some studies questioned the usefulness of vedolizumab TDM ( Pouillon et al, 2019 ) because data are heterogeneous and impede the definition of a clear therapeutic range, while the drug has a low potential for immunogenicity.…”

Section: Monoclonal Antibodies Used In Inflammatory Bowel Diseasesmentioning

confidence: 99%

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

Paolo

Luci

2021

Front. Pharmacol.

View full text Add to dashboard Cite

The pharmacotherapy of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) has experienced significant progress with the advent of monoclonal antibodies (mABs). As therapeutic proteins, mABs display peculiar pharmacokinetic characteristics that differentiate them from chemical drugs, such as aminosalicylates, antimetabolites (i.e., azathioprine, 6-mercaptopurine, and methotrexate), and immunosuppressants (corticosteroids and cyclosporine). However, clinical trials have demonstrated that biologic agents may suffer from a pharmacokinetic variability that could influence the desired clinical outcome, beyond primary resistance phenomena. Therefore, therapeutic drug monitoring (TDM) protocols have been elaborated and applied to adaptation drug doses according to the desired plasma concentrations of mABs. This activity is aimed at maximizing the beneficial effects of mABs while sparing patients from toxicities. However, some aspects of TDM are still under discussion, including time-changing therapeutic ranges, proactive and reactive approaches, the performance and availability of instrumental platforms, the widely varying individual characteristics of patients, the severity of the disease, and the coadministration of immunomodulatory drugs. Facing these issues, personalized medicine in IBD may benefit from a combined approach, made by TDM protocols and pharmacogenetic analyses in a timeline that necessarily considers the frailty of patients, the chronic administration of drugs, and the possible worsening of the disease. Therefore, the present review presents and discusses the activities of TDM protocols using mABs in light of the most recent results, with special attention on the integration of other actions aimed at exploiting the most effective and safe therapeutic effects of drugs prescribed in IBD patients.

show abstract

“…Systematic review with meta-analysis by Singh et al [97] found that vedolizumab trough concentration >20 μg/mL at week 6 and >12 μg/mL during maintenance may be associated with better clinical outcomes. However, in patients with CD, there was no significant difference in median vedolizumab trough concentrations in patients achieving clinical remission or endoscopic remission.…”

Section: Evolving Paradigmsmentioning

confidence: 99%

Vedolizumab in Inflammatory Bowel Disease: West versus East

Debnath¹,

Rathi²

2021

Inflamm Intest Dis

View full text Add to dashboard Cite

Background: Vedolizumab is a humanized immunoglobulin G1 monoclonal antibody, which binds to α4β7 integrin on T lymphocytes, thus disturbing the interaction with mucosal vascular addressin cell adhesion molecule 1 on the intestinal endothelial cells to interfere with lymphocyte trafficking to the gut. Summary: Vedolizumab is a safe and effective drug to induce and maintain clinical remission in patients with Crohn’s disease (CD) and ulcerative colitis (UC) in both clinical trials and real-world data. Various guidelines recommend vedolizumab as a first- or second-line treatment regimen for steroid-dependent, steroid, or immunomodulator refractory cases of UC and CD; however, it is more effective in anti-TNF-naive patients. The first head-to-head trial (VARSITY trial) comparing the efficacy of vedolizumab to adalimumab has shown better clinical remission and mucosal healing with vedolizumab. Key Messages: In this review, we have discussed guidelines recommendation of vedolizumab use, as well as its safety data, use in special population, in presence of extraintestinal complications, therapeutic drug monitoring, data from Asian patients, along with other evolving concepts. Because of its excellent safety data and low immunogenicity, vedolizumab is an impressive option for patients with prior malignancy and less chance of reactivation of tuberculosis; however, cost remains an issue.

show abstract

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Cited by 46 publications

References 30 publications

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease

Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond

Vedolizumab in Inflammatory Bowel Disease: West versus East

Contact Info

Product

Resources

About