CD4+ count-dependent concentration-effect relationship of rituximab in rheumatoid arthritis.
Adult
Aged
Aged, 80 and over
Antirheumatic Agents
/ administration & dosage
Arthritis, Rheumatoid
/ blood
Biomarkers
/ analysis
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes
/ drug effects
Dose-Response Relationship, Drug
Female
Half-Life
Humans
Male
Markov Chains
Middle Aged
Models, Biological
Retrospective Studies
Rituximab
/ administration & dosage
Treatment Outcome
T-lymphocytes
pharmacodynamics
pharmacokinetics
rheumatoid arthritis
rituximab
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
29
03
2019
revised:
29
07
2019
accepted:
13
08
2019
pubmed:
28
8
2019
medline:
29
9
2020
entrez:
28
8
2019
Statut:
ppublish
Résumé
Rituximab 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. In 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. Elimination 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. This 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.
Identifiants
pubmed: 31454097
doi: 10.1111/bcp.14102
pmc: PMC6955400
doi:
Substances chimiques
Antirheumatic Agents
0
Biomarkers
0
Rituximab
4F4X42SYQ6
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2747-2758Informations de copyright
© 2019 The British Pharmacological Society.
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