ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives

Abstract

The ANCA associated vasculitides (AAVs) affect a range of internal organs including ear nose and throat, respiratory tract, kidneys, skin and nervous system. They include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). The AAVs are treated with high dose glucocorticoids, immunosuppressants, and targeted biological medications. Since the 1990s classification criteria for the AAVs have been based on clinical features, laboratory tests and basic imaging; an initiative to update the classification criteria incorporating newer tests, for example, anti-neutrophil cytoplasmic antibodies (ANCA) and novel imaging techniques will be published this year. There is also evidence for classification of patients based on ANCA subtype; those with anti-proteinase 3 antibodies (PR3) or anti-myeloperoxidase antibodies (MPO) have differences in response to treatment and clinical outcomes. An update is described within this review. The pathogenesis of AAV involves necrotizing inflammation of small to medium blood vessels involving multiple immunological pathways. We present an update on emerging evidence related to auto-antibodies, complement and lymphocyte pathways. This review describes emerging treatment regimens, including evidence for plasma exchange in severe disease and the inhibitor of the complement C5a receptor (C5aR) inhibitor, Avacopan. Lastly, patient reported outcomes are key secondary outcomes in randomised controlled trials and increasingly clinical practice, we report development in disease specific and glucocorticoid-specific PROs.

ANCA Associated Vasculitis Subtypes: Response [Letter]

“…However, we respectfully want to elaborate on one statement in the article. 1 In the management section, the authors reference the ADVOCATE trial and suggest that background immunosuppressive therapy and ANCA type should influence decisions on use of avacopan to treat ANCA-associated vasculitis.…”

“…However, we respectfully want to elaborate on one statement in the article. 1 In the management section, the authors reference the ADVOCATE trial and suggest that background immunosuppressive therapy and ANCA type should influence decisions on use of avacopan to treat ANCA-associated vasculitis.ADVOCATE was a randomized, double-blind, double-dummy trial conducted in 143 study centers in 20 countries in which avacopan replaced an oral prednisone taper regimen in a standard of care regimen for ANCA-associated vasculitis. 2 The choice of background immunosuppressive therapy was not randomized, and the study was not powered, nor the analyses designed, to determine the efficacy of avacopan based on background immunosuppressive therapy.…”

ANCA Associated Vasculitis Subtypes: Response [Response to Letter]

“…Many thanks for the opportunity to respond to the interesting letter to the Editor from Merkel, Jayne, and Bekker, with regard to our publication “ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives”. 1 …”

“…

Many thanks for the opportunity to respond to the interesting letter to the Editor from Merkel, Jayne, and Bekker, with regard to our publication "ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives". 1 In the management section of our review article, we highlighted some examples of where "personalized" treatment could be explored further in trials of ANCA associated vasculitis.Our main evidence in terms of the influence of serotype on disease outcomes was in relation to the RAVE study, ie, PR3-ANCA cases responding better to Rituximab than cyclophosphamide in terms of long-term outcomes. 2 We did, however, also reference the ADVOCATE study and appreciate that, in doing so, we could have been clearer about our meaning.

…”

“…Many thanks for the opportunity to respond to the interesting letter to the Editor from Merkel, Jayne, and Bekker, with regard to our publication "ANCA Associated Vasculitis Subtypes: Recent Insights and Future Perspectives". 1 In the management section of our review article, we highlighted some examples of where "personalized" treatment could be explored further in trials of ANCA associated vasculitis.…”