Trial reportClinical pharmacokinetics2020
Non-Linear Rituximab Pharmacokinetics and Complex Relationship between Rituximab Concentrations and Anti-Neutrophil Cytoplasmic Antibodies (ANCA) in ANCA-Associated Vasculitis: The RAVE Trial Revisited.
Trial report in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- The pharmacokinetics and its covariates of rituximab in different clinical populations: a systematic review and narrative synthesis.European journal of clinical pharmacology · 2026Pooled it
- Translating B-Cell and Plasma-Cell Targeting from Oncology to Autoimmunity: Modalities, Quantitative Bridging, and a Development Roadmap.Clinical pharmacology and therapeutics · 2026Review
- Pharmacokinetic Characterization of Rituximab in Patients with Glomerular Diseases.Therapeutic drug monitoring · 2025Article
- Immunoglobulin G Receptors (FcγR), in Addition to Target-Antigen and Neonatal Fc Receptor (FcRn), Influence Rituximab Pharmacokinetics.Clinical pharmacokinetics · 2025Article
- Article
- Antibody Drug Clearance: An Underexplored Marker of Outcomes with Checkpoint Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Dosing optimization of rituximab for primary membranous nephropathy by population pharmacokinetic and pharmacodynamic study.Frontiers in pharmacology · 2024Article
- Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence.Kidney international reports · 2024Article
- Very low doses of rituximab in autoimmune hemolytic anemia-an open-label, phase II pilot trial.Frontiers in medicine · 2024Article
- Relationship Between Cetuximab Target-Mediated Pharmacokinetics and Progression-Free Survival in Metastatic Colorectal Cancer Patients.Clinical pharmacokinetics · 2023Article
- The Influence of Underlying Disease on Rituximab Pharmacokinetics May be Explained by Target-Mediated Drug Disposition.Clinical pharmacokinetics · 2022Article
- Implications of rituximab pharmacokinetic and pharmacodynamic alterations in various immune-mediated glomerulopathies and potential anti-CD20 therapy alternatives.Frontiers in immunology · 2022Review
- Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-associated Vasculitis.The Journal of rheumatology · 2021Article
- Pharmacokinetic Variability of Therapeutic Antibodies in Humans: A Comprehensive Review of Population Pharmacokinetic Modeling Publications.Clinical pharmacokinetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesRituximab is approved in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and leads to a decrease of ANCA levels. The objectives of this study were to investigate the non-linear pharmacokinetics of rituximab and the relationship between its concentrations and ANCA levels in AAV patients.
methodsNinety-two AAV patients from the RAVE (Rituximab in ANCA-Associated Vasculitis) trial were assessed. Both ANCA anti-myeloperoxidase (MPO-ANCA) and anti-proteinase 3 (PR3-ANCA) levels were used as biomarkers. The pharmacokinetics of rituximab were described using a semi-mechanistic two-compartment model that included a latent target antigen turnover and allowed the estimation of specific target-mediated elimination in addition to its non-specific elimination of rituximab. The effect of rituximab on the ANCA level was described using a semi-mechanistic compartment model with a negative feedback (Friberg) model with no transit compartment. A population modeling approach was used.
resultsOur pharmacokinetic and pharmacokinetic-pharmacodynamic (PK-PD) models satisfactorily described both concentration-time and concentration-effect relationship data. The mean (inter-individual standard deviation) estimated non-specific clearance was 0.15 L/day (0.30%) and the target-mediated elimination rate constant was 2.4 × 10
conclusionsA non-linear target-mediated elimination of rituximab was detected in AAV patients. Our PK-PD model allowed quantification of the association between rituximab concentrations and ANCA levels. This decrease was deep but delayed, and more sustained in patients with MPO-ANCA than in those with PR3-ANCA. Our results suggest that repeating courses of rituximab might improve the clinical response to rituximab.
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