Evidence map›Paper›PMID 34351609›Full record

ArticleClinical pharmacokinetics2022

Infliximab Treatment Does Not Lead to Full TNF-α Inhibition: A Target-Mediated Drug Disposition Model.

David Ternant, Marc Pfister, Olivier Le Tilly, Denis Mulleman, Laurence Picon, Stéphanie Willot, Christophe Passot, Theodora Bejan-Angoulvant, Thierry Lecomte, Gilles Paintaud and 1 more

Abstract read
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In one paragraph

Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Physiological Considerations for ModelingFrontiers in pharmacology · 2022
    Review
  6. Article
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

11 authors at 4 institutions in 2 countries.

David TernantPediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland. david.ternant@univ-tours.fr.ORCID 0000-0003-4020-4545
Marc PfisterPediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
Olivier Le TillyEA 4245 'Transplantation, Immunology, Inflammation', Université de Tours, Tours, France.
Denis MullemanEA 7501 'Groupe Innovation et Ciblage Cellulaire', Université de Tours, Tours, France.
Laurence PiconDepartment of Gastroenterology, CHRU de Tours, Tours, France.
Stéphanie WillotDepartment of Paediatrics, CHRU de Tours, Tours, France.
Christophe PassotDépartement de Biopathologie, Institut de Cancérologie de l'Ouest, Angers, France.
Theodora Bejan-AngoulvantEA 4245 'Transplantation, Immunology, Inflammation', Université de Tours, Tours, France.
Thierry LecomteEA 7501 'Groupe Innovation et Ciblage Cellulaire', Université de Tours, Tours, France.
Gilles PaintaudEA 4245 'Transplantation, Immunology, Inflammation', Université de Tours, Tours, France.
Gilbert KochPediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
Université de Tours · FRCentre Hospitalier Universitaire de Tours · FRUniversity of Basel · CHInstitut de Cancérologie de l'Ouest · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveInfliximab, an anti-tumour necrosis factor (TNF)-α monoclonal antibody, has been approved in chronic inflammatory disease, including rheumatoid arthritis, Crohn's disease and ankylosing spondylitis. This study aimed to investigate and characterise target-mediated drug disposition of infliximab and antigen mass turnover during infliximab treatment.

methodsIn this retrospective cohort of 186 patients treated with infliximab for rheumatoid arthritis, Crohn's disease or ankylosing spondylitis, trough infliximab concentrations were determined from samples collected between weeks 0 and 22 after treatment initiation. Target-mediated pharmacokinetics of infliximab was described using target-mediated drug disposition modelling. Target-mediated elimination parameters were determined for rheumatoid arthritis and Crohn's disease, assuming ankylosing spondylitis with no target-mediated elimination.

resultsThe quasi-equilibrium approximation of a target-mediated drug disposition model allowed a satisfactory description of infliximab concentration-time data. Estimated baseline TNF-α amounts were similar in Crohn's disease and rheumatoid arthritis (R0 = 0.39 vs 0.46 nM, respectively), but infliximab-TNF complex elimination was slower in Crohn's disease than in rheumatoid arthritis (k

conclusionsThe present study is the first to quantify the influence of target antigen dynamics on infliximab pharmacokinetics. Target-mediated elimination of infliximab may be complex, involving a multi-scale turnover of TNF-α, especially in patients with Crohn's disease. Additional clinical studies are warranted to further evaluate and fine-tune dosing approaches to ensure sustained TNF-α inhibition.

Indexed as

Antirheumatic AgentsPharmaceutical PreparationsAntibodies, MonoclonalHumansInfliximabRetrospective StudiesTumor Necrosis Factor-alphaAntibodies, MonoclonalAntirheumatic AgentsInfliximabPharmaceutical PreparationsTumor Necrosis Factor-alpha

Identifiers

PMID34351609
OpenAlexW3192567839

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.