Targeted immunotherapy strategies in ANCA-associated vasculitis.

Abstract

Targeted immunotherapy is substantially improving the management of ANCA-associated vasculitides (AAV), which include granulomatosis with polyangiitis (GPA, Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). This article reviews the current role for targeted immunotherapy in AAV, its validated indications, and avenues for further development. Rituximab is a validated induction treatment for GPA and severe MPA. Rituximab in these indications is not less effective than cyclophosphamide and is particularly useful in patients with refractory or relapsing disease, women of childbearing potential, and patients previously treated with cyclophosphamide. Rituximab is more effective than cyclophosphamide for treating relapses. For remission maintenance therapy, which is indispensable, rituximab has been proven superior over conventional immunosuppressive treatment. Rituximab is licensed in the USA and in Europe for the induction treatment of severe forms of GPA and MPA. An extension study for remission maintenance therapy is ongoing. In EGPA, although maintenance treatment with the interleukin-5 antagonist mepolizumab is effective in decreasing glucocorticoid requirements and in alleviating asthma and sinonasal symptoms, its efficacy on the vasculitis remains somewhat unclear. Mepolizumab is licensed for use in EGPA, and rituximab is also being evaluated as an induction and maintenance agent. Immunoglobulins can be helpful as an adjuvant treatment for active AAV with severe immunedepression, notably when infections occur. Plasma exchange is indicated in AAV with advanced renal dysfunction and, perhaps, in the event of alveolar hemorrhage, a possibility that will be assessed in 2018 in a large international study.

• Authors: Xavier Puéchal
• Journal: Joint bone spine (Joint Bone Spine) Vol. 86 Issue 3 Pg. 321-326 (05 2019) ISSN: 1778-7254 [Electronic] France
• PMID: 30201478 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biological Products
• Immunosuppressive Agents
• Rituximab
• Cyclophosphamide
• mepolizumab

Topics

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (diagnosis, drug therapy)
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Biological Products (therapeutic use)
• Cyclophosphamide (administration & dosage)
• Female
• France
• Humans
• Immunosuppressive Agents (administration & dosage)
• Immunotherapy (methods)
• Male
• Molecular Targeted Therapy (methods)
• Plasma Exchange
• Remission Induction
• Risk Assessment
• Rituximab (administration & dosage)
• Treatment Outcome