TAVAB: Therapy of autoantibody-mediated diseases with Bortezomib
In spite of different clinical manifestations a number of autoimmune diseases have in common that their pathogenesis is mainly due to the production of autoantibodies and that their long-term therapy is based on corticosteroids and additional immunosuppressive drugs.
However, especially the so called „long-lived“ plasma cells, that produce the autoantibodies and are responsible for disease chronicity due to their ability to persist for many years or even lifelong, are especially resistant to current therapeutic options. Therefore, a cure for these diseases is not possible and the long-term immune suppression that is necessary for disease stabilization often results in a multitude of serious side effects. On the other hand a significant fraction of patients does not sufficiently respond to current therapy. Consequently, new therapeutic options for these diseases are urgently needed.
The proteasome inhibitor Bortezomib that is characterized by a plasma cell specific mechanism has already been licensed for some years for the therapy of multiple myeloma, a malignant plasma cell tumor. The mechanism of action is based on the inhibition of the proteasome which leads to programmed cell death (apoptosis) especially in cell types with a high protein turnover like plasma cells. Recent data in experimental systems show a significant therapeutic effect of Bortezomib also in autoantibody mediated diseases. However, so far this has not been proven in a clinical study in humans.
Therefore, in our study a small number of patients suffering from Myasthenia Gravis (MG), Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), all refractory to current standard therapy, were treated with Bortezomib (Velcade®). During the study we analyzed the disease specific antibody titers, disease activity, disease related quality of life and a number of other parameters. We hoped that based on this study we will be able to offer new therapeutic options for these patients.
Principle Investigator: Prof. Falk Hiepe (Dept. of Rheumatology, Charité) and Prof. Andreas Meisel (Dept. of Neurology, Charité).
Registration: This study is registered in the database clinicaltrials.gov (NCT02102594)
Kohler, S., M. Losen, T. Alexander, F. Hiepe, and A. Meisel. "Myasthenia Gravis: Subgroup Classifications." Lancet Neurol 15, no. 4 (Apr 2016): 356-7. https://doi.org/10.1016/S1474-4422(16)00033-8. Link
Kohler, S., S. Marschenz, U. Grittner, T. Alexander, F. Hiepe, and A. Meisel. "Bortezomib in Antibody-Mediated Autoimmune Diseases (Tavab): Study Protocol for a Unicentric, Non-Randomised, Non-Placebo Controlled Trial." BMJ Open 9, no. 1 (Jan 28 2019): e024523. Link