1.
Long-term outcomes of patients treated with rituximab as second-line treatment for adult immune thrombocytopenia - Follow-up of the RITP study
Tjonnfjord E, Holme PA, Darne B, Khelif A, Waage A, Michel M, Ben Romdhan N, Ghanima W
Br J Haematol. 2020
Abstract
RITP was a double-blind randomized, 78-week follow-up trial in which 109 adults with immune thrombocytopenias (ITP) who failed to achieve adequate response to steroids, were randomized to receive rituximab or placebo. Here, we provide the duration of response, splenectomy and mortality rates based on extended follow-up after completion of the RITP study. Extended follow-up data were retrospectively collected for 72 (83%) patients out of the 84 patients who were not splenectomized during the initial RITP study. For the present analysis, median [interquartile range] duration of follow-up after randomization was 72 [62-82] months. Median duration of response among patients who achieved an initial response was significantly longer in patients who received rituximab (8.2 [5.5-16.7] months) as compared to placebo (1.8 [1.3-3.6] months), P = 0.036. Overall, 35 patients underwent splenectomy (13 in the rituximab, and 22 in the placebo arm, P = 0.12). Eleven patients (10%) died during the study: five in the rituximab and six in the placebo arms, including four deaths from severe bleeding. Although most rituximab-treated patients eventually relapsed, a longer duration of response and a trend towards lower splenectomy rate were observed in rituximab-treated patients.
2.
Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect
Mathijssen NC, Masereeuw R, Holme PA, van Kraaij MG, Laros-van Gorkom BA, Peyvandi F, van Heerde WL
Thrombosis Research. 2013;132((2):):256-62.
Abstract
INTRODUCTION Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. MATERIALS AND METHODS Ten factor VII deficient patients were treated with either recombinant activated (20mug/kg) or plasma-derived (25IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. RESULTS Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236ml/kg; 175ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206ml/kg; 64ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. CONCLUSIONS Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright 2013 Elsevier Ltd. All rights reserved.