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Pharmacokinetics of rituximab and clinical outcomes in patients with anti-neutrophil cytoplasmic antibody associated vasculitis.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2018 Apr 01; Vol. 57 (4), pp. 639-650. - Publication Year :
- 2018
-
Abstract
- Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes.<br />Methods: This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by computing the trapezoidal area under the curve. We explored potential determinants of the PK-RTX, and analysed its association with clinical outcomes: achievement of remission at 6 months, duration of B-cell depletion and time to relapse in patients who achieved complete remission.<br />Results: RTX serum levels were significantly lower in males and in newly diagnosed patients, and negatively correlated with body surface area, baseline B-cell count and degree of disease activity. In multivariate analyses, the main determinants of PK-RTX were sex and new diagnosis. Patients reaching complete remission at month 6 had similar RTX levels compared with patients who did not reach complete remission. Patients with higher RTX levels generally experienced longer B-cell depletion than patients with lower levels, but RTX levels at the different time points and area under the curve were not associated with time to relapse.<br />Conclusion: Despite the body-surface-area-based dosing protocol, PK-RTX is highly variable among patients with AAV, its main determinants being sex and newly diagnosed disease. We did not observe any relevant association between PK-RTX and clinical outcomes. The monitoring of serum RTX levels does not seem clinically useful in AAV.
- Subjects :
- Adult
Aged
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis blood
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis immunology
B-Lymphocytes immunology
B-Lymphocytes pathology
Dose-Response Relationship, Drug
Double-Blind Method
Female
Humans
Immunologic Factors administration & dosage
Immunologic Factors pharmacokinetics
Infusions, Intravenous
Lymphocyte Count
Male
Middle Aged
Remission Induction
Rituximab administration & dosage
Treatment Outcome
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis drug therapy
Rituximab pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 57
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 29340623
- Full Text :
- https://doi.org/10.1093/rheumatology/kex484