A novel dosing approach for rituximab in glomerular diseases based on a population pharmacokinetic analysis
Language English Country France Media print-electronic
Document type Journal Article
PubMed
38678967
DOI
10.1016/j.biopha.2024.116655
PII: S0753-3322(24)00539-0
Knihovny.cz E-resources
- Keywords
- ANCA associated vasculitis, Focal-segmental glomerulosclerosis, Lupus nephritis, Membranous nephropathy, Minimal change disease, Nephrotic syndrome, Proteinuria,
- MeSH
- Models, Biological MeSH
- Adult MeSH
- Glomerulonephritis drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Glomerulonephritis, Membranous drug therapy MeSH
- Young Adult MeSH
- Rituximab * pharmacokinetics administration & dosage therapeutic use MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Rituximab * MeSH
OBJECTIVES: Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. METHODS: We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients' characteristics, rituximab levels and anti-rituximab antibodies. RESULTS: The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. CONCLUSION: In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.
References provided by Crossref.org
Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies
