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
- They cause vascular damage and necrosis to primarily small vessels, leading to organ failure
Organ pathology from vascular injury leads to:
- 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.
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.
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.