Comparison of outcomes using the rituximab originator MabThera with the biosimilar Truxima in patients with ANCA-associated vasculitis.

OBJECTIVES: The use of rituximab (MabThera®), an anti-CD20 monoclonal antibody, is the most significant development in the management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) since the introduction of cytotoxic therapy in 1950. Truxima® is the first anti-CD20 biosimilar approved for the same indications, and has been available in the UK since 2017. Significant cost savings have been reported when switching to biosimilars, which could lead to greater patient access to such treatment. Therefore, it is important to know whether patients' clinical and laboratory parameters respond equally well to biosimilars as to reference medicines, tested in clinical trials. METHOD: We retrospectively reviewed the clinical outcomes and laboratory parameters in 257 consecutive patients treated with anti-CD20 depletion therapy using MabThera or Truxima, for induction and maintenance of remission, in two tertiary renal centres between 2010 and 2019. RESULTS: We demonstrated no difference between patients treated with MabThera or Truxima in rates of remission, relapse, and hospitalization with infection when used for either induction or maintenance of remission of AAV. In one hospital subgroup analysis, we showed comparable levels of hypogammaglobulinaemia, B-cell depletion, and frequency of infusion reactions, with no significant differences. CONCLUSION: The efficacy and safety of the rituximab biosimilar Truxima are not inferior to the originator MabThera in patients with AAV. Truxima represents a cheaper and safe therapeutic alternative that could increase patient access to rituximab.

Outgrowth in vitro of cervical epithelium separated from the uterovaginal anlage of newborn mice. An ultrastructural study.

After gently trypsinization, the pseudostratified columnar Müllerian epithelium that lines the uterine cervix of newborn mice could be separated from the enclosing stromal tissue Pure epithelial tubes explanted in vitro and were allowed to grow in a standard medium for 3-4 days forming a confluent colony of rather closely-fitting cells. The cell sheet was studied by a preparatory technique that allows examination of a large number of cells with preserved intercellular spatial orientation. Attempts were made to identify cultured cells according to the morphology of cell types in the cervicovaginal epithelium in vivo. Electron micrographs revealed that, close to the explant, the cultured cell sheet exhibited several features similar to the Müllerian epithelium in vivo. Outside these central areas of the colony was a broad transitional zone consisting of thin platelike cells distinguished by an abundance of microfilaments. At the periphery of the colonies, bulky cells possessing microvilli and a vacuolated cytoplasm tended to overlpa adjoining platelike cells. These bulky cells had a morphology resembling that of the superficial cells seen in the upper vagina and common cervical canal of immature and diestrous animals. The epithelial development in the cultures apparently simulated the transformation iatified epithelium resembling that of the uppermost vagina and common cervical canal of immature animals. Judged by morphological and cytochemical criteria, the Müllerian cells in the out-growth obviously had many changed features. It thus seems questionable wheter the cells grown in vitro are comparable with the corresponding cells in vivo when used for experiments requiring the corresponding of the culture environment.

Heparin effects on cultured mammalian cells.

Plasmacytoma cells exposed to heparin exhibited zeiotic blebs in the G1 phase, S phase, and early G2 phase. Zeiosis was not seen in mitotic cells. This heparin effect was reversible. Also fibroblasts were sensitive to heparin. After trypsinization of fibroblasts, heparin produced large non-reversible zeiotic blebs in the cells, except in those in mitosis. The primary target for heparin is apparently to be sought among components of the cellular periphery.