PROPOSED MECHANISM OF ACTION IN GPA & MPA

What are granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)?

  • GPA (formerly known as Wegener's Granulomatosis) and MPA are two forms of systemic vasculitis[9]
  • They cause vascular damage and necrosis to primarily small vessels, leading to organ failure[1]

Organ pathology from vascular injury leads to[10]:

  • Ischemia
  • Hemorrhage
  • Loss of organ function

What are antineutrophil cytoplasmic antibodies (ANCAs)?

Patients with ANCA-associated vasculitides often have antibodies to specific neutrophil cytoplasmic proteins[9,10]

  • ANCAs directed to proteinase 3 (PR3) are predominantly associated with GPA
  • ANCAs directed to myeloperoxidase (MPO) are more frequently associated with MPA

ANCA titers may fluctuate over the course of the disease.[10]

Historical standard of care for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)

Cyclophosphamide (CYC), in combination with steroids, has been a commonly prescribed treatment regimen for patients with Granulomatosis with Polyangiitis and Microscopic Polyangiitis.[14]

In 2011, the FDA approved Rituxan, in combination with glucocorticoids, for the induction treatment of adult patients with Granulomatosis with Polyangiitis and Microscopic Polyangiitis.

ANCA-associated vasculitis-induced necrotizing vasculitis in GPA and MPA

B cells produce ANCAs, which play a pathogenic role in GPA and MPA.

ANCA, antineutrophil cytoplasmic antibody; MPO, myeloperoxidase; PR3, proteinase 3.