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Targeting B Cells in ANCA-Associated Vasculitides

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Drugs Targeting B-Cells in Autoimmune Diseases

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

ANCA-associated vasculitides (AAV) is defined as vasculitides associated with anti-neutrophil cytoplasmic antibody (ANCA) serum positivity affecting small and medium-sized vessels. Glomerulonephritis in AAV is typified by focal necrosis, crescent formation, and few or no immunoglobulin deposits. In vitro and animal evidence suggests that ANCA play a pathogenic role in AAV. Specific gene expression signatures are reported to predict long-term prognosis in AAV, suggesting that therapy might be personalized and new therapeutic targets identified. Although immunosuppressant agents and glucocorticosteroids are the basis of AAV therapy, the results of randomized controlled trials show that rituximab is not inferior to cyclophosphamide (CYC) in inducing remission in patients with severe AAV. In 2011, the US Food and Drug Administration (FDA) approved rituximab plus glucocorticosteroids as a front-line therapy for adults with granulomatosis with polyangiitis (Wegener’s granulomatosis) and microscopic polyangiitis. This new indication for rituximab represents the first ever FDA-approved therapy for these two diseases and the first alternative to CYC for the treatment of severe disease in nearly four decades. However, questions regarding the use of maintenance therapy after rituximab, the concurrent use of CYC and the toxicity of rituximab remain to be answered in current and future randomized trials.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, Hospital Clínic, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Xavier Bosch

  2. Division of Rheumatology, Allergy & Immunology, Rheumatology Unit, Harvard Medical School, Massachusetts General Hospital, Yawkey 2, 55 Fruit Street, Boston, MA, 02114, USA

    John H. Stone

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  1. Xavier Bosch
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Correspondence to John H. Stone .

Editor information

Editors and Affiliations

  1. Hospital Clinic, Department of Internal Medicine, University of Barcelona, Barcelona, Spain

    Xavier Bosch

  2. Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain

    Manuel Ramos-Casals

  3. King's College, The Rayne Institute, St. Thomas' Hospital, London, United Kingdom

    Munther A Khamashta

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© 2014 Springer Basel

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Bosch, X., Stone, J.H. (2014). Targeting B Cells in ANCA-Associated Vasculitides. In: Bosch, X., Ramos-Casals, M., Khamashta, M. (eds) Drugs Targeting B-Cells in Autoimmune Diseases. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0348-0706-7_8

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