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Atherosclerosis is a progressive disorder that leads to the thickening and narrowing of arterial walls due to plaque buildup. This condition can cause various symptoms depending on the arteries affected:Coronary Artery Disease (CAD): This condition affects the coronary arteries and may lead to chest pain (angina), shortness of breath (dyspnea), heart attacks, and other heart disease symptoms.Cerebrovascular Disease: This affects blood flow to the brain, causing transient ischemic attacks (TIAs)...
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[ANCA-associated vasculitis].

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Avacopan significantly reduces glucocorticoid use in ANCA-associated vasculitis remission induction. Prolonged rituximab maintenance and targeted EGPA therapies show promise for improved patient outcomes.

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Area of Science:

  • Nephrology
  • Rheumatology
  • Immunology

Background:

  • Glucocorticoids (GCs) are standard for inducing remission in Granulomatous with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), but cause significant toxicity.
  • Rituximab is effective for maintenance therapy in ANCA-associated vasculitis (AAV), but optimal duration is unclear.
  • Eosinophilic Granulomatosis with Polyangiitis (EGPA) is increasingly recognized as having distinct phenotypes, suggesting targeted therapies.

Purpose of the Study:

  • To evaluate avacopan's efficacy in reducing glucocorticoid burden during induction of remission for GPA and MPA.
  • To assess the optimal duration of rituximab maintenance therapy in AAV.
  • To explore genetic underpinnings of EGPA phenotypes and evaluate targeted therapies.

Main Methods:

  • The ADVOCATE trial demonstrated avacopan's effect on glucocorticoid reduction during remission induction.
  • The PEXIVAS trial compared reduced-dose glucocorticoids with and without plasma exchange for remission induction.
  • The MAINRITSAN 3 study investigated prolonged rituximab maintenance, and a Genome-Wide Association Study (GWAS) analyzed EGPA patient genetics.

Main Results:

  • Avacopan allows substantial glucocorticoid reduction in GPA/MPA induction.
  • Reduced-dose glucocorticoids (up to 60% reduction) were as effective as standard doses for induction, with no added benefit from plasma exchange.
  • Prolonged rituximab use (>2 years) is beneficial for AAV maintenance.
  • GWAS in EGPA supports distinct "vasculitic" and "eosinophilic" subgroups, with mepolizumab showing clinical benefit for the latter.

Conclusions:

  • Avacopan is likely to play a future role in GPA and MPA induction therapy, enabling significant glucocorticoid sparing.
  • Plasma exchange is largely obsolete for induction of remission in GPA/MPA.
  • Longer-term rituximab maintenance and targeted therapies like mepolizumab for EGPA represent advances in AAV management.