Docteur JULIEN MELET

Bibliographie

• Antigenic burden and serum IgG concentrations influence rituximab pharmacokinetics in rheumatoid arthritis patients

  2017

  ArticleBritish Journal of Clinical Pharmacology

Source : HAL — archive ouverte CCSD/CNRS (couvre articles, chapitres EMC, communications congrès, thèses).

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Top publications · les plus citées

• 1

  Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response

  Arthritis and rheumatism · 2013

  📚 123 citations🎯 RCR 3.89Top 11% NIH

  Lire l'abstract Crossref ↓

  Objective Rituximab, a monoclonal antibody specifically targeting CD20, induces B cell depletion and is effective in the treatment of rheumatoid arthritis (RA). This study was undertaken to evaluate whether routine monitoring of lymphocyte subpopulations, especially T cells, may be useful in patients receiving rituximab for RA. Methods We examined data on all RA patients receiving rituximab between July 2007 and November 2012 in our center. Peripheral blood CD3+, CD4+, CD8+, CD3−CD56+, and CD19+ lymphocyte counts before and during the first course of rituximab were measured by flow cytometry. The Mann‐Whitney nonparametric test was used to compare lymphocyte subpopulation counts before and during treatment. Results Data on 52 patients were examined. Rituximab induced unexpected and substantial depletion of T cells, mainly CD4+ cells, in most patients. The CD4+ cell count decreased by a mean ± SD of 37 ± 33% as compared to baseline at week 12, reaching <200 cells/μl in 3 patients. Importantly, lack of CD4+ cell depletion was associated with no clinical response. Therefore, the mechanism of action of rituximab may depend at least in part on T cells. Conclusion Rituximab induces substantial T cell depletion, mainly of CD4+ cells, which is associated with the clinical response in RA. Routine monitoring of T cells may be useful in the clinical setting of RA.

• 2

  Antigenic burden and serum IgG concentrations influence rituximab pharmacokinetics in rheumatoid arthritis patients

  British journal of clinical pharmacology · 2017

  📚 32 citations🎯 RCR 1.56🔓 Open Access📄 PDF gratuit ↗

  Lire l'abstract Crossref ↓

  AimsRituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target‐antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients.MethodsIn a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis.ResultsA two‐compartment model, with first‐order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day–1, respectively. Distribution and elimination half‐lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k10) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10−8), and that k10 decreased with time (P = 0.00015), partly explained by a change in target‐antigen amount.ConclusionsThe association between CD19+ count and k10 may be explained by target‐mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.

Publications scientifiques (2) — classées par pathologie

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