Avacopan, a Novel Competitive C5a Receptor Antagonist, for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Clin Drug Investig. 2023 Aug;43(8):595-603. doi: 10.1007/s40261-023-01298-z. Epub 2023 Aug 18.

Abstract

Avacopan is a relatively novel drug with complement antagonizing properties, and it has demonstrated promising outcomes in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. This review article seeks to investigate the current standard of care for ANCA vasculitis with the combination of avacopan. The current standard therapy involves the usage of daily corticosteroids in addition to either cyclophosphamide or rituximab; however, prolonged use of corticosteroids is known to be associated with various adverse effects. Avacopan was introduced as a possible substitution to alleviate high-corticosteroid dosages. It functions through competitive inhibition of the C5a receptor in the complement system and results in the reduction of neutrophil activation and migration to sites of inflammation. Clinical trials have observed the efficacy of avacopan both in conjunction with standard therapy with corticosteroids and without corticosteroids. The use of avacopan was able to achieve disease remission and improve renal function in patients with ANCA-associated vasculitis. Additionally, the novel treatment did not increase the risk of adverse events during treatment, while also lowering the toxic effects associated with corticosteroid usage. In summary, current evidence supports the success and safety of administering avacopan to treat patients with ANCA-associated vasculitis. Additional clinical trials are warranted to identify optimal dosage and method in using avacopan in the clinical setting.

Publication types

  • Review

MeSH terms

  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis* / drug therapy
  • Antibodies, Antineutrophil Cytoplasmic*
  • Humans
  • Inflammation
  • Receptor, Anaphylatoxin C5a

Substances

  • avacopan
  • Antibodies, Antineutrophil Cytoplasmic
  • Receptor, Anaphylatoxin C5a