ANCA-associated vasculitis-treatment standard

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are characterized by small-vessel necrotizing inflammation, and prior to the advent of immunosuppressive therapy frequently had a fatal outcome. Treatment has transformed AAV into a relapsing/remitting disease with increased drug-related toxicities and organ damage. The use of glucocorticoids, cyclophosphamide and immunosuppressives (including azathioprine, mycophenolate and methotrexate) was optimized through a sequence of clinical trials establishing a standard of care against which subsequent targeted therapies could be developed. Improved understanding of pathophysiology has supported the development of B-cell depletion and complement inhibition in granulomatosis with polyangiitis and microscopic polyangiitis, and interleukin 5 inhibition for eosinophilic granulomatosis with polyangiitis, leading to the approval of newer agents for these conditions. There has been an increased attention on minimizing the adverse effects of treatment and on understanding the epidemiology of comorbidities in AAV. This review will focus on recent evidence from clinical trials, especially with respect to glucocorticoids, avacopan, plasma exchange, rituximab and mepolizumab, and their interpretation in the 2022 management recommendations by the European League of Associations of Rheumatology.

Keywords: ANCA-associated vasculitis; diagnosis; pathophysiology; prognosis; treatment.

Figure 1:

Proposed therapeutic algorithm for the management of GPA and MPA. GC, glucocorticoid; RTX, rituximab; CYC, cyclophosphamide; MMF, mycophenolate mofetil; MTX, methotrexate; IVIG, intravenous immunoglobulin; AZA, azathioprine; TMP-SMX, trimethoprim/sulfamethoxazole.

Figure 2:

Proposed therapeutic algorithm for the management of EGPA. GC, glucocorticoid; RTX, rituximab; CYC, cyclophosphamide; AZA, azathioprine; MTX, methotrexate; MMF, mycophenolate mofetil; MEPO, mepolizumab; TMP-SMX, trimethoprim/sulfamethoxazole.

Figure 3:

Pathogenesis of AAV and potential targeted therapies. TNF, tumor necrosis factor alpha; IL-1, interleukin-1; IL-5R, interleukin 5 receptor; Th2, T helper 2 cells; avacopan, target C5aR; vilobelimab, target C5a; belimumab, target BAFF/Blys; rituximab, target CD20; obinutuzumab, target CD20; abatacept, ligand-binding domain of CTLA4; mepolizumab, target IL-5; benralizumab; target IL-5R.