Evidence map›Paper›PMID 25996351›Full record

Trial reportAlimentary pharmacology & therapeutics2015

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

M Rosario, N L Dirks, M R Gastonguay, A A Fasanmade, T Wyant, A Parikh, W J Sandborn, B G Feagan, W Reinisch, I Fox

Erratum issued 5 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase IIClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alimentary pharmacology & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 5 registered trials, which are not on this map. Cited by 133 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 5 pooled it
20.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00783692 phase3completednot on this map

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2008 to 2012Enrolled1,116ConditionsCrohn's DiseaseArmsvedolizumab, Placebo
NCT00783718 phase3completednot on this map

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2009 to 2012Enrolled895ConditionsUlcerative ColitisArmsvedolizumab, Placebo
NCT01177228 phase2completednot on this map

A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MLN0002 Following Multiple Intravenous Doses in Patients With Ulcerative Colitis

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2007 to 2008Enrolled47ConditionsUlcerative ColitisArmsVedolizumab, Placebo
NCT01224171 phase3completednot on this map

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn's Disease

TypeinterventionalSponsorMillennium Pharmaceuticals, Inc.Ran2010 to 2012Enrolled416ConditionsCrohn's DiseaseArmsvedolizumab, Placebo
NCT03802214 terminatednot on this mapstarted 2020, after this paper: background citation

A Case-control Study to Evaluate the Immunoinflammatory Effect of Prior Exposure to Anti-TNF Therapy in Patients With Ulcerative Colitis Starting Vedolizumab Therapy

TypeobservationalSponsorStanford UniversityRan2020 to 2020Enrolled1ConditionsUlcerative ColitisArmsVedolizumab
3 · Its place in the literature

Who cites it

133 citing papers in PubMed, 5 syntheses or guidelines pooled it, 255 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Trial
  19. Article
  20. Article

73 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 3 countries.

M RosarioTakeda Pharmaceuticals International Co., Cambridge, MA, USA.
N L DirksMetrum Research Group LLC, Tariffville, CT, USA.
M R GastonguayMetrum Research Group LLC, Tariffville, CT, USA.
A A FasanmadeTakeda Pharmaceuticals International Co., Cambridge, MA, USA.
T WyantTakeda Pharmaceuticals International Co., Cambridge, MA, USA.
A ParikhTakeda Pharmaceuticals International, Inc., Deerfield, IL, USA.
W J SandbornDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
B G FeaganRobarts Research Institute, University of Western Ontario, London, ON, Canada.
W ReinischDepartment Internal Medicine III, Medical University of Vienna, Vienna, Austria.
I FoxTakeda Pharmaceuticals International Co., Cambridge, MA, USA.
Takeda (United States) · USMetrum Research Group (United States) · USMedical University of Vienna · ATUniversity of California, San Diego · USWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing.

aimsTo characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling.

methodsData from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data.

resultsVedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L).

conclusionsPopulation pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3).

Indexed as

AdolescentAdultAgedAlbuminsAntibodies, Monoclonal, HumanizedBody WeightColitis, UlcerativeCrohn DiseaseFemaleGastrointestinal AgentsHalf-LifeHealthy VolunteersHumansInflammatory Bowel DiseasesMaleMetabolic Clearance RateAlbuminsAntibodies, Monoclonal, HumanizedGastrointestinal Agentsvedolizumab

Identifiers

PMID25996351
PMCPMC5032981
OpenAlexW1940516511

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.