Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2015
[Pemphigus. Model disease for targeted therapy].
Аннотация на английскомСтатьяОбзорНазвание и аннотация: Перевод пока не подготовлен
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Eming R
Аннотация
BACKGROUND: Pemphigus is a severe bullous autoimmune dermatosis that represents a clinical challenge despite high-dose immunosuppressive therapy due to the therapy-related comorbidities and the lack of long-term control of disease activity.
OBJECTIVES: Which targeted therapies are currently used in pemphigus and which innovative therapeutic strategies are in clinical development?
MATERIALS AND METHODS: A review of the literature in PubMed was performed under consideration of the current guideline for the treatment of pemphigus as well as of our own results. Discussion of basic findings and results of targeted therapies in autoantibody-mediated autoimmune disorders were taken into account.
RESULTS: Immunapheresis and high-dose intravenous immunoglobulins with the aim of reducing circulating autoantibodies have been successfully used in the treatment of pemphigus. Depletion of autoreactive B-lymphocytes provides the rationale for the use of the monoclonal anti-CD20 antibody rituximab which demonstrated long-term clinical remission of pemphigus in clinical trials. Current developments include the investigation of humanised B-cell depleting antibodies in other B-cell driven autoimmune disorders as well as the identification of new cellular and molecular target structures that are essential in the humoral autoimmune cascade and exert important immune regulatory functions, respectively.
CONCLUSIONS: The well-characterised basic pathogenesis of pemphigus results in targeted therapies. Currently, therapies aiming at rapid reduction of circulating autoantibodies and the depletion of autoreactive B-cells are in clinical use. More cellular and molecular target structures are being investigated in other autoantibody-driven autoimmune disorders and they provide promising candidates for innovative pathogenesis-related therapeutic strategies in pemphigus in the future.
OBJECTIVES: Which targeted therapies are currently used in pemphigus and which innovative therapeutic strategies are in clinical development?
MATERIALS AND METHODS: A review of the literature in PubMed was performed under consideration of the current guideline for the treatment of pemphigus as well as of our own results. Discussion of basic findings and results of targeted therapies in autoantibody-mediated autoimmune disorders were taken into account.
RESULTS: Immunapheresis and high-dose intravenous immunoglobulins with the aim of reducing circulating autoantibodies have been successfully used in the treatment of pemphigus. Depletion of autoreactive B-lymphocytes provides the rationale for the use of the monoclonal anti-CD20 antibody rituximab which demonstrated long-term clinical remission of pemphigus in clinical trials. Current developments include the investigation of humanised B-cell depleting antibodies in other B-cell driven autoimmune disorders as well as the identification of new cellular and molecular target structures that are essential in the humoral autoimmune cascade and exert important immune regulatory functions, respectively.
CONCLUSIONS: The well-characterised basic pathogenesis of pemphigus results in targeted therapies. Currently, therapies aiming at rapid reduction of circulating autoantibodies and the depletion of autoreactive B-cells are in clinical use. More cellular and molecular target structures are being investigated in other autoantibody-driven autoimmune disorders and they provide promising candidates for innovative pathogenesis-related therapeutic strategies in pemphigus in the future.