Evidence map›Paper›PMID 31454097›Full record

Observational studyBritish journal of clinical pharmacology2019

CD4+ count-dependent concentration-effect relationship of rituximab in rheumatoid arthritis.

Amina Bensalem, Denis Mulleman, Gilles Thibault, Nicolas Azzopardi, Philippe Goupille, Gilles Paintaud, David Ternant

Open access · bronzeAbstract readObservational Study
In one paragraph

Observational study in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

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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 1 institution in 1 country.

Amina BensalemEA 7501 GICC, Université de Tours, Tours, France.
Denis MullemanEA 7501 GICC, Université de Tours, Tours, France.
Gilles ThibaultEA 7501 GICC, Université de Tours, Tours, France.
Nicolas AzzopardiEA 7501 GICC, Université de Tours, Tours, France.
Philippe GoupilleEA 7501 GICC, Université de Tours, Tours, France.
Gilles PaintaudEA 7501 GICC, Université de Tours, Tours, France.
David TernantEA 7501 GICC, Université de Tours, Tours, France.ORCID 0000-0003-4020-4545
Université de Tours · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsRituximab is approved in rheumatoid arthritis (RA). A substantial decrease in CD4+ count was observed in responders after a single cycle of treatment. This study aimed to describe and quantifying the influence of CD4+ count depletion on the concentration-response relationship of rituximab in RA patients.

methodsIn this retrospective monocentric observational study, 52 patients were assessed. Repeated measurements of rituximab concentrations (pharmacokinetics), CD4+ counts (biomarker) and disease activity score in 28 joints (DAS28, clinical response) were made. Rituximab pharmacokinetics was described using a 2-compartment model, and CD4+ cell counts and DAS28 measurements were described using indirect turnover and direct Emax pharmacokinetic-pharmacodynamic models, respectively. Delay between rituximab concentrations and responses was accounted for by including biophase compartments.

resultsElimination half-life of rituximab was 18 days. The pharmacokinetic-pharmacodynamic model showed that DAS28 response to rituximab was partly associated with CD4+ cell depletion. At 6 months, a deeper DAS28 decrease was observed in patients when CD4+ cell count is decreased: median [interquartile range] of DAS28 was 3.7 [2.9-4.4] and 4.5 [3.7-5.3] in patients with and without CD4+ decrease, respectively.

conclusionsThis is the first study to quantify the relationship between rituximab concentrations, CD4+ count and DAS28 in RA patients. This model showed that approximately 75% of patients had CD4+ count decrease, and that the clinical improvement is 2-fold higher in patients with CD4+ cells decrease than in others.

Indexed as

Models, BiologicalAdultAgedAged, 80 and overAntirheumatic AgentsArthritis, RheumatoidBiomarkersCD4 Lymphocyte CountCD4-Positive T-LymphocytesDose-Response Relationship, DrugFemaleHalf-LifeHumansMaleMarkov ChainsMiddle AgedAntirheumatic AgentsBiomarkersRituximabpharmacodynamicspharmacokineticsrheumatoid arthritisrituximabT-lymphocytes

Identifiers

PMID31454097
PMCPMC6955400
OpenAlexW2970898160

What OpenQuestion holds

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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.