B cell therapy in ANCA-associated vasculitis: current and emerging treatment options.

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an organ-threatening and life-threatening multi-system autoimmune disease in which B cell-derived ANCAs cause neutrophil activation and endothelial damage, strongly implicating these autoantibodies in the pathogenesis of AAV. B cell depletion with rituximab combined with glucocorticoids is associated with a reduction in ANCA concentrations and with clinical remission in the majority of patients with AAV. However, the safety profile of rituximab is no better than that of conventional therapy with cyclophosphamide, and long-term glucocorticoid treatment is needed to achieve and maintain disease-free remission. A need for new therapies exists to reduce the time to remission, to spare the use of glucocorticoids and to promote long-lasting remission without the risk of relapse. Over the past 20 years, there has been great interest in therapeutically targeting B cell cytokines, such as B cell-activating factor (BAFF), in many autoimmune disease settings. Dual B cell-targeted immunotherapy that combines B cell depletion and BAFF blockade could potentially be more efficacious than targeting either mechanism alone. In this Review, the theoretical background for use of this combination approach in AAV is presented and discussed.

• Authors: Mark McClure, Seerapani Gopaluni, David Jayne, Rachel Jones
• Journal: Nature reviews. Rheumatology (Nat Rev Rheumatol) Vol. 14 Issue 10 Pg. 580-591 (10 2018) ISSN: 1759-4804 [Electronic] United States
• PMID: 30108367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antibodies, Monoclonal, Humanized
• B-Cell Activating Factor
• Glucocorticoids
• TNFSF13B protein, human
• Rituximab
• belimumab

Topics

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy, immunology)
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• B-Cell Activating Factor (antagonists & inhibitors)
• B-Lymphocytes (drug effects, immunology)
• Clinical Trials as Topic
• Drug Therapy, Combination
• Glucocorticoids (pharmacology, therapeutic use)
• Humans
• Immunotherapy (methods)
• Molecular Targeted Therapy
• Rituximab (pharmacology, therapeutic use)
• Treatment Outcome