[The role of rituximab in the treatment of ANCA-associated systemic vasculitis].
A considerable minority of patients with ANCA-associated small-vessel vasculitis are refractory to conventional therapy or experience dose-limiting side effects. Novel therapeutic approaches include rituximab, a genetically engineered chimeric murine-human monoclonal antibody that binds to CD20, which is expressed on human B cells. It was approved in 1997 for the treatment of CD20-positive B-cell non-Hodgkin lymphoma and in 2006 for the treatment of rheumatoid arthritis. The multiple mechanisms proposed for rituximab-mediated B-cell depletion are discussed in this paper. Cumulative data from several open studies on the treatment of microscopic ANCA-associated polyangiitis suggest that in the vast majority of cases rituximab has a beneficial effect. Two randomized controlled trials confirmed these promising results, suggesting that rituximab might be considered as an option for first-line therapy of induction of remission of ANCA-associated vasculitis, and providing an additional tool for treating patients with disease relapse after previous therapy. While rituximab is very effective in the depletion of B cells, current research suggests it could also influence other immune system cells and reestablish immune homeostasis and tolerance. The safety profile of rituximab reveals that most reactions are infusion-related and that the incidence of serious side effects is low. Systemic infection remains a major concern and may result in death. A small number of cases of progressive multifocal leukoencephalopathy reported in patients receiving rituximab in off-label use (albeit none with ANCA-associated vasculitis) highlights the importance of pharmacovigilance.
Centro di Ricerche di Immunopatologia e Documentazione su Malattie Rare, Ospedale G. Bosco e Universita di Torino, Torino, Italy. dario.roccatello@unito.it
Dario
D
Roccatello
Alba
A
Vangelista
Antonello
A
Pani
D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003131:Combined Modality Therapy; D004198:Disease Susceptibility; D004359:Drug Therapy, Combination; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016867:Immunocompromised Host; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000209:etiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology; D008212:Lymphocyte Depletion; D015337:Multicenter Studies as Topic; D010956:Plasmapheresis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D000069283:Rituximab