Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease

Dulai, Parambir S.; Boland, Brigid S.; Singh, Siddharth; Chaudrey, Khadija; Koliani-Pace, Jenna L.; Kochhar, Gursimran; Parikh, Malav P.; Shmidt, Eugenia; Hartke, Justin; Chilukuri, Prianka; Meserve, Joseph; Whitehead, Diana; Hirten, Robert; Winters, Adam C.; Katta, Leah; Peerani, Farhad; Narula, Neeraj; Sultan, Keith; Swaminath, Arun; Bohm, Matthew; Lukin, Dana J.; Hudesman, David; Chang, John T.; Rivera–Nieves, Jesús; Jairath, Vipul; G, Zou; Feagan, Brian G.; Shen, Bo; Siegel, Corey A.; Loftus, Edward V.; Kane, Sunanda V.; Sands, Bruce E.; Colombel, Jean Fréd́eric; Sandborn, William J.; Lasch, Karen; Cao, Charles

doi:10.1053/j.gastro.2018.05.039

Cited by 109 publications

(97 citation statements)

References 36 publications

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“…Methodology for the development and validation of our CDST has been published previously. 13 In the current study, individual participant data from the phase 3 VDZ in CD trial (GEMINI 2) were used in combination with observational cohort data from the VICTORY consortium and GETAID collaboration. 14,15 A treat-straight-through cohort was created from the GEMINI 2 clinical trial programs to mimic an observational cohort design.…”

Section: Data Sources and Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The VICTORY consortium investigators previously developed and validated a clinical decision support tool (CDST) that classifies CD patients according to low, intermediate and high probability of response to VDZ. 13 In the current analysis, we used the GEMINI 2 clinical trial data (NCT00783692) to assess whether these differences were related to differences in measured VDZ concentrations (exposure-efficacy) and whether the CDST predicts differences in rapidity of onset of action. We subsequently performed a second external validation of the CDST based on data from a prospective cohort study (GETAID) and then, using data from both the GETAID and VICTORY cohorts, assessed whether the CDST accurately identified patients who might benefit from dose intensification.…”

Section: Introductionmentioning

confidence: 99%

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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

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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,

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Section: Data Sources and Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

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“…Genetic backgrounds and phenotypes of inflammatory bowel disease differ considerably between Asian and Western patients [10,11]; it is therefore important to determine treatment targets, outcomes, and responses in populations with different genetic backgrounds [12]. Multivariable analysis of GEMINI 2 data identified that ethnicity was a predictive factor of remission (American Indian or Alaskan Native, Asian, Black, and Native Hawaiian or other Pacific Islander vs non-Hispanic/Latino; odds ratio [OR] and 95% confidence interval [CI], 0.30 [0.12-0.75]) [13], and a post hoc analysis of data from GEMINI 2 and 3 also showed that race (non-White vs White) tended to predict rapid response to vedolizumab at Week 2 [14]. Therefore, it is meaningful to evaluate vedolizumab efficacy and associated predictive factors in patients with CD who are of different race to the more widely studied Western patient population.…”

Section: Introductionmentioning

confidence: 99%

Effects of vedolizumab in Japanese patients with Crohn’s disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses

et al. 2019

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Background Vedolizumab is a gut-selective humanized antibody that binds the a 4 b 7 integrin. We evaluated efficacy and safety of vedolizumab in Japanese patients with moderate-to-severe Crohn's disease (CD). Methods In this Phase 3, double-blind study (NCT02038920), 157 patients were randomized to receive intravenous vedolizumab 300 mg (n = 79) or placebo (n = 78) at Weeks 0, 2, and 6 (induction phase). Patients with CD activity index (CDAI)-70 response at Week 10 were randomized to receive vedolizumab 300 mg (n = 12) or placebo (n = 12) at Week 14, then every 8 weeks until Week 54 (maintenance phase). Primary endpoints were C 100-point reduction in CDAI (CDAI-100 response) at

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“…In clinical settings, morphological MRI coupled to molecular imaging of MAdCAM-1 could allow fast, sensitive and non-invasive evaluation of mucosal lesions, thereby alleviating the need for endoscopy and improving patient comfort and safety. The ability to detect MAdCAM-1 could also be key for the identification of patients candidate for MAdCAM-1 targeted therapies such as vedolizumab( 24 ). Beyond mucosal lesions, this method has also the potential to improve the diagnosis of other disorders involving dysregulation of MAdCAM-1 such as pancreatic cancers( 25 ) or chronic inflammatory liver disease( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Ultrasensitive Molecular Imaging of Mucosal Inflammation Using Leucocyte-Mimicking Particles Targeted to MAdCAM-1

Fournier

Lizarrondo

Rateau

et al. 2019

Preprint

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One Sentence Summary: Molecular magnetic resonance imaging allows non-invasive evaluation of mucosal inflammation in clinically relevant experimental models. ABSTRACTMucosal tissues line the digestive, respiratory, urinary, mammary and reproductive tracts and play critical roles in health and disease as the primary barrier between the external world and the inner body. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, that causes significant patient discomfort and can lead to organ damage. Here, we developed a new contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this new technique can detect low, subclinical levels of mucosal inflammation.Molecular MRI of MAdCAM-1 has thus potential applications in early diagnosis, longitudinal follow-up and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.Recently, we and others reported the use of a new family of contrast agents for molecular MRI based on micro-sized particles of iron oxide (MPIO) that displays a dramatically higher sensitivity than classically used nano-sized particles(9-12). Thanks to an artefact known as the blooming effect, MPIO appear around 50 times larger than their actual size on iron sensitive T2*-weighted images (12). This characteristic of MPIO makes them particularly interesting for imaging mucosal tissues, since these tissues measure only a few hundred micrometers of thickness in physiological conditions and are thus hardly visible on unenhanced MRI. In the present study in mice, we developed a new MPIO-based contrast agent for MRI targeted to MAdCAM-1 (thereafter named MPIO-αMAdCAM-1). In three different models of intestinal inflammation, including lipopolysaccharides (LPS) induced endothelial activation, dextran sodium sulfate (DSS) induced colitis and trinitrobenzene sulfonic acid (TNBS) induced colitis(13), we demonstrated that this contrast agent allows detection of mucosal inflammation, quantification of disease activity and assessment of the mucosal response to anti-inflammatory treatments.

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Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease

Abstract: We developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.

Cited by 109 publications

References 36 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

Effects of vedolizumab in Japanese patients with Crohn’s disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses

Ultrasensitive Molecular Imaging of Mucosal Inflammation Using Leucocyte-Mimicking Particles Targeted to MAdCAM-1

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