Vifor Pharma: Can outcomes in ANCA Associated Vasculitis be improved by targeting disease mechanisms?


Valkenburg
English
Satellite Symposium
05 June 2020 08:15 - 09:45

ANCA associated vasculitis is a severe systemic small vessel vasculitis and all nephrologists are involved in patient care whether with acute glomerulonephritis, long term follow up or managing the vasculitis patient receiving renal replacement therapy. Therefore this symposium concerning this severe disease will be of broad interest to EULAR attendees and will focus on new clinical and scientific evidence to meet the following educational objectives; 

  • To explain the underlying pathophysiology of the vasculitic process in ANCA associated vasculitis and in particular the amplification loop with the interaction between neutrophils and the activated alternative complement system. 

  • To review the latest clinical trial evidence and real world data to show the unmet medical needs around achieving and sustaining remission, the harm from high dose and prolonged lower dose glucocorticoids and the adverse impact of renal involvement  

  • To describe how new therapies could target the underlying interaction between complement and neutrophils and achieve control of vasculitis activity while avoiding glucocorticoid induced harm. 

Overall outcomes in ANCA associated vasculitis have improved from the 1970s but current treatment guidelines  for remission induction (ERA-EDTA/EULAR, Yates 2016) focus on the use of a combination of high dose glucocorticoids and either rituximab or cyclophosphamide. This yields a variable remission rate and an over reliance on glucocorticoids to achieve and maintain remission (Bruchfeld 2019). This symposium will focus on the progress in our understanding of the underlying causes of ANCA associated vasculitis and how this can lead to the development of targeted therapeutic advances in this debilitating long term condition.

 

Drivers of the vasculitic process - how do neutrophils and the complement system interact?  

This presentation will focus on the underlying pathophysiology of ANCA associated vasculitis. The loss of autoimmunity leading to the development of ANCA is due to an interaction between environment and genetic factors which have become more clear with recent GWAS (Lee 2019). The pathophysiological role of ANCA will be described and in particular how they can activate the innate immune system following neutrophil priming (Jennette 2017). Although seemingly counterintuitive to the description of the pauci-immune glomerunephritis in ANCA associated vasculitis, the alternative complement pathway is activated – the consequences which lead to intense vascular inflammation will be described with evidence from pre-clinical models and clinical studies. The terminal effector protein C5a is critically involved in this process and is a potential therapeutic target. 

  

Unmet needs in ANCA associated vasculitis - can they be met with a targeted therapy?  

The unmet needs in ANCA associated vasculitis will be described and the adverse impact on patient experience emphasized. Current treatment regimes allow approximately 60% of patients to be in remission without need for glucocorticoids at 6 months of remission induction treatment (Stone 2010) but this drops to approximately 43% at 12 months (Specks 2013). The accompanying high acute mortality and elevated long term mortality risk will be described (Flossman 2010). The risks of renal involvement are significant and the burden of ESRF and the cumulative organ damage from vasculitis and adverse impact of glucocorticoids will be reviewed (Robson 2015). The presentation will then link to the underlying pathophysiology of ANCA associated vasculitis described in the first presentation. The potential therapeutic approach to block the alternative complement cascade will be described (Jayne 2017) and potential advantages for vasculitis control, renal disease and quality of life reviewed. The presentation will finish with a description of the ADVOCATE study (Merkel 2018) which is comparing avacopan (a specific C5a receptor 1 antagonist) with glucocorticoids for achieving and maintaining remission. This randomised controlled trial included 331 ANCA associated vasculitis patients, many in Europe, and was completed in late 2019 offering potentially a new option for clinicians, targeted at the underlying causes of the disease.  


Presentations

Title Time Add to calendar
Welcome & Introduction
05 June 2020 08:15 - 08:15 Add to calendar
Drivers of the vasculitic process - how do neutrophils and the complement system interact?
05 June 2020 08:15 - 08:45 Add to calendar
Unmet needs in ANCA associated vasculitis - can they be met with a targeted therapy?
05 June 2020 08:45 - 09:15 Add to calendar
Q&A and Closing
05 June 2020 09:15 - 09:15 Add to calendar