{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:28:27Z","timestamp":1791170907341,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T00:00:00Z","timestamp":1248134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Serum concentrations of rituximab influence its clinical efficacy in follicular lymphoma (FL), but its concentration\u2013effect relationship has not been described by pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) modelling.<\/jats:p><jats:p>\u2022\u2003The genetic polymorphism of <jats:italic>FCGR3A<\/jats:italic> influences rituximab efficacy and its <jats:italic>in vitro<\/jats:italic> concentration\u2013effect relationship.<\/jats:p><jats:p>\u2022\u2003Increasing rituximab dose and\/or number of infusions may lead to a better clinical response in FL.<\/jats:p><jats:p> <jats:bold>WHAT THIS PAPER ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003This study is the first to describe the concentration\u2013effect relationship of rituximab in populations of FL patients.<\/jats:p><jats:p>\u2022\u2003This PK\u2013PD model relates progression\u2010free survival with rituximab concentrations and takes into account the influence of <jats:italic>FCGR3A<\/jats:italic> polymorphism.<\/jats:p><jats:p>\u2022\u2003Clinical trials testing new dosing regimens of rituximab can be designed using this PK\u2013PD model.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIM<\/jats:title><jats:p>Rituximab has dramatically improved the survival of patients with non\u2010Hodgkin's lymphomas (NHL), but the dosing regimen currently used should be optimized. However, the concentration\u2013effect relationship of rituximab has never been described by pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) modelling, precluding the simulation of new dosing regimens. The aim of this study was to develop a PK\u2013PD model of rituximab in relapsed\/resistant follicular NHL (FL).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A model describing the relationship between rituximab concentrations and progression\u2010free survival (PFS) was developed using data extracted from the pivotal study, which evaluated 151 relapsed\/resistant FL patients. The influence of FCGR3A genetic polymorphism on the efficacy of rituximab was quantified using data from 87 relapsed\/resistant FL patients. The predictive performance of the model was analysed using two independent datasets: a study that evaluated rituximab combined with chemotherapy [rituximab, cyclophosphamide, vincristine, adriamycin and prednisone (R\u2010CHOP)] in 334 relapsed\/resistant FL patients and a study that evaluated rituximab monotherapy in 47 asymptomatic FL patients with known FCGR3A genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>For R\u2010CHOP, observed and model\u2010predicted PFS (90% confidence interval) at 24 months were 0.50 and 0.48 (0.40, 0.56), respectively, for the observation arm, and 0.62 and 0.59 (0.50, 0.65), respectively, for the rituximab maintenance arm. For rituximab monotherapy, observed and predicted PFS at 24 months were 0.67 and 0.63, respectively, for <jats:italic>FCGR3A<\/jats:italic>\u2010V\/V patients, and 0.41 and 0.36 (0.25, 0.49), respectively, for <jats:italic>FCGR3A<\/jats:italic>\u2010F carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Our model provides a satisfactory prediction of PFS at 24 months. It can be used to simulate new dosing regimens of rituximab in populations of FL patients and should improve the design of future clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2009.03494.x","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T18:18:19Z","timestamp":1248200299000},"page":"561-573","source":"Crossref","is-referenced-by-count":21,"title":["Development of a drug\u2013disease simulation model for rituximab in follicular non\u2010Hodgkin's 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