Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody‐mediated disease

Abstract

Aims Both rituximab and plasmapheresis can be associated in the treatment of immune‐mediated kidney diseases. The real impact of plasmapheresis on rituximab pharmacokinetics is unknown. The aim of this study was to compare rituximab pharmacokinetics between patients requiring plasmapheresis and others without plasmapheresis. Methods The study included 20 patients receiving one or several infusions of rituximab. In 10 patients, plasmapheresis sessions were also performed (between two and six sessions per patient). Rituximab concentrations were measured in blood samples in all patients and in discarded plasma obtained by plasmapheresis using an enzyme‐linked immunosorbent assay method. Data were analysed according to a population pharmacokinetic approach. Results The mean percentage of rituximab removed during the first plasmapheresis session ranged between 47 and 54% when plasmapheresis was performed between 24 and 72 h after rituximab infusion. Rituximab pharmacokinetics was adequately described by a two‐compartment model with first‐order elimination. Plasmapheresis had a significant impact on rituximab pharmacokinetics, with an increase of rituximab clearance by a factor of 261 (95% confidence interval 146–376), i.e. from 6.64 to 1733 ml h−1. Plasmapheresis performed 24 h after rituximab infusion decreased the rituximab area under the curve by 26%. Conclusions Plasmapheresis removed an important amount of rituximab when performed less than 3 days after infusion. The removal of rituximab led to a significant decrease of the area under the curve. This pharmacokinetic observation should be taken into account for rituximab dosing, e.g. an additional third rituximab infusion may be recommended when three plasmapheresis sessions are performed after the first rituximab infusion.

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

“…Several studies have shown a remarkable increase in RIT clearance in thrombotic thrombocytopenic purpura or kidney transplant recipients by TPE performed within 1-3 days of RIT infusion (28,29); however, these studies did not analyze the impact of TPE on the therapeutic efficacy of RIT. Darabi et al (30) suggested that regularly scheduled TPE did not diminish the immunosuppressive effects of RIT due to the rapid effects of RIT on circulating CD20þ in a study with two thrombocytopenic purpura patients who were given RIT 24-36 hours before TPE.…”

Nonlinear pharmacokinetics of rituximab in non‐Hodgkin lymphomas: A pilot study

“…The pharmacokinetics of rituximab were described in 12 pharmacokinetic modelling studies in NHL, CLL and rheumatoid arthritis . and in patients under plasmapherisis . Some of these studies suggested that rituximab pharmacokinetics might be influenced by antigen mass (i.e.…”

Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study

“…In this context, rituximab was shown to hasten platelet count recovery, reduce plasma Additional Supporting Information may be found in the online version of this article. 1 Service de M edecine Interne, CHU Charles Nicolle, Rouen; 2 Inserm U1096, Rouen, France; 3 Hôpital Saint-Antoine, AP-HP, Centre de R ef erence des Microangiopathies Thrombotiques, Paris, France; 4 Universit e François-Rabelais de Tours, CNRS, GICC UMR 7292, CHRU de Tours, Laboratoire de Pharmacologie-Toxicologie, Tours, France; 5 Hôpital Saint-Louis, AP-HP, Service de R eanimation M edicale, Paris, France; 6 Universit e Paris Diderot, Sorbonne Paris Cit e, Paris, France; 7 Hôpital de Marseille Conception, Service d'H emaph erèse, Marseille, France; 8 Hôpital Saint-Louis, AP-HP, Service d'Immunologie Clinique, Paris, France; 9 CHU Saint-Antoine, AP-HP, Service de R eanimation M edicale, Paris, France; 10 Sorbonne Universit e, UPMC Univ Paris 06, Paris, France; 11 Urgences n ephrologiques et transplantation r enale, Hôpital Tenon, AP-HP, Paris, France; 12 Hôpital Cochin, AP-HP, Service de R eanimation Polyvalente, Paris, France; 13 Universit e Paris 5, Paris, France; 14 Hôpital Sud, Service de N ephrologie-M edecine Interne, Amiens, France; 15 Service de M edecine interne 1, Hôpital La Piti e-Salpêtrière, AP-HP, Paris, France; 16 Service de M edecine interne, CHU de Fort-de France, France; 17 Hôpital Saint-Antoine, AP-HP, Unit e de Recherche Clinique de l'Est Parisien (URC-Est), Paris, France; 18 CHU Saint-Antoine, AP-HP, Service d'Immunologie et H ematologie biologique, Paris, France; 19 Hôpital Lariboisière, AP-HP, Service d'H ematologie Biologique, Paris, France; requirement and decrease the 1-year relapse rate by diminishing the production of anti-ADAMTS13 and restoring ADAMTS13 activity [9,10,12]. Additionally, preemptive rituximab infusions administered to patients with a persistent severe ADAMTS13 deficiency during TTP remission efficiently prevent long-term relapses [13].…”