Evidence map›Paper›PMID 29159893›Full record

ArticleAlimentary pharmacology & therapeutics2018

Exposure-response relationship of certolizumab pegol induction and maintenance therapy in patients with Crohn's disease.

N Vande Casteele, B G Feagan, S Vermeire, M Yassine, J Coarse, G Kosutic, W J Sandborn

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alimentary pharmacology & therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 5% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
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  3. A Clinical Prediction Model to Determine Probability of Response to Certolizumab Pegol for Crohn's Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

N Vande CasteeleDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-0854-0274
B G FeaganRobarts Clinical Trials, Western University, London, ON, Canada.
S VermeireTranslational Research in GastroIntestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
M YassineUCB Pharma, Smyrna, GA, USA.
J CoarseUCB Pharma, Raleigh, NC, USA.
G KosuticUCB Pharma, Raleigh, NC, USA.
W J SandbornDivision of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
UCB Pharma (United States) · USWestern University · CAKU Leuven · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTherapeutic drug monitoring may optimize therapy for Crohn's disease (CD).

aimTo use a population pharmacokinetic model that accounts for the time-varying nature of covariates to simulate certolizumab pegol (CZP) concentrations to evaluate the exposure-response relationship for CZP in Crohn's disease.

methodsAdults (N = 2157) with Crohn's disease were treated with CZP in nine clinical trials. Simulated CZP concentrations were compared to outcomes at weeks 6 and 26, including Crohn's disease activity index (CDAI) response (decrease from baseline ≥ 100 points), remission (CDAI ≤ 150), C-reactive protein (CRP) ≤ 5 mg/L, faecal calprotectin (FC) ≤ 250 μg/g, and a composite endpoint of CDAI ≤ 150 and FC ≤ 250 μg/g. Multivariable analyses identified covariates associated with outcomes and receiver operating characteristic analyses determined optimal CZP concentrations.

resultsCZP concentrations at weeks 2, 4 and 6 were higher in patients with clinical response, remission, CRP ≤ 5 mg/L or FC ≤ 250 μg/g at week 6 than without. In multivariable analyses, higher CZP concentrations at week 6 were associated with the composite outcome at weeks 6 and 26 (P < .001). Although the exposure-response relationship varied among patients, approximate CZP concentrations of at least 36.1 μg/mL (positive predictive value [PPV] 22.8% and negative predictive value [NPV] 92.7%) and at least 14.8 μg/mL (PPV 28.0% and NPV 90.4%) at weeks 6 and 12 were associated with weeks 6 and 26 outcomes.

conclusionsAn exposure-response relationship was apparent for CZP in Crohn's disease and achieving higher CZP concentrations may increase the likelihood of attaining efficacy outcomes, but this remains to be evaluated prospectively.

Indexed as

Induction ChemotherapyMaintenance ChemotherapyAdultCertolizumab PegolClinical Trials as TopicCrohn DiseaseDrug MonitoringFemaleHumansMalePrognosisTreatment OutcomeCertolizumab Pegol

Identifiers

PMID29159893
PMCPMC5765392
OpenAlexW2769684727

What OpenQuestion holds

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Registered trials

None linked

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.