Evidence map›Paper›PMID 28353055›Full record

ArticleClinical pharmacokinetics2017

Accounting for Pharmacokinetic Variability of Certolizumab Pegol in Patients with Crohn's Disease.

Niels Vande Casteele, Diane R Mould, Jason Coarse, Iram Hasan, Ann Gils, Brian Feagan, William J Sandborn

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03765450 (Pharmacokinetics of Infliximab and Tumor Necrosis Factor Concentrations in Serum, Stool, and Colonic Mucosa in Acute Severe Ulcerative Colitis), which is not on this map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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.

NCT03765450 active not recruitingnot on this mapstarted 2018, after this paper: background citation

Pharmacokinetics of Infliximab and Tumor Necrosis Factor Concentrations in Serum, Stool, and Colonic Mucosa in Acute Severe Ulcerative Colitis

TypeobservationalSponsorAlimentiv Inc.Ran2018 to 2027Enrolled18ConditionsUlcerative ColitisArmsInfliximab
3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. 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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  17. Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019
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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.

Niels Vande CasteeleDivision of Gastroenterology, School of Medicine, IBD Center, University of California San Diego, 9500 Gilman Drive #0956, La Jolla, CA, 92093, USA. nvandecasteele@ucsd.edu.
Diane R MouldProjections Research Inc., Phoenixville, PA, USA.
Jason CoarseUCB Pharma, Raleigh, NC, USA.
Iram HasanUCB Pharma, Raleigh, NC, USA.
Ann GilsDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Louvain, Belgium.
Brian FeaganRobarts Research Institute, London, ON, Canada.
William J SandbornDivision of Gastroenterology, School of Medicine, IBD Center, University of California San Diego, 9500 Gilman Drive #0956, La Jolla, CA, 92093, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCertolizumab pegol is an effective biologic for patients with Crohn's disease (CD). Individual differences in certolizumab pegol apparent clearance (CL/F) affect exposure and possibly efficacy. A previously developed population pharmacokinetic (PK) model did not account for dynamic changes in clinical parameters during therapy.

objectiveThe aim of this study was to refine the existing PK model to capture the time-varying influence of covariates.

methodsData collected from 2157 Crohn's disease patients in nine studies were analyzed using nonlinear mixed-effects modeling software (NONMEM). Certolizumab pegol concentration-time data were described by a one-compartment PK model with first-order absorption, and one-compartment disposition with linear, time-dependent elimination using antidrug antibody (ADAb) concentration as a continuous variable.

resultsThe final dataset consisted of 12,926 analyzable records. Parameter estimates were absorption rate constant 1.83/day, CL/F 0.527 L/day, and apparent volume of distribution (V/F) 8.33 L. ADAb concentration (2.5-214 units/mL) increased the median CL/F by 142-174%. For a typical patient, body weight (46.8-100.5 kg) increased the median CL/F and V/F from 82 to 120%. Albumin (32-48 g/L) decreased and C-reactive protein (0.5-54.0 mg/L) increased the median CL/F from 123 to 85% and from 83 to 113%, respectively. Between-patient variability of CL/F was 19.6%.

conclusionsBy incorporating time-varying covariates, this population PK model reduces between-patient variability on CL/F estimates, and the relative influence of ADAb can now be assessed. As Crohn's disease patient covariates are often time-dependent, this model is more reflective of patient drug exposure with sustained treatment.

Indexed as

Models, BiologicalAdolescentAdultAgedAged, 80 and overAntibodiesCertolizumab PegolClinical Trials as TopicC-Reactive ProteinCrohn DiseaseFemaleHumansImmunosuppressive AgentsLinear ModelsMaleMiddle AgedAntibodiesCertolizumab PegolC-Reactive ProteinImmunosuppressive AgentsSerum Albumin, Human

Identifiers

PMID28353055

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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.