Avacopan in the treatment of ANCA-associated vasculitis

ABSTRACT

Introduction: ANCA-associated vasculitis (AAV) is a rare but potentially life-threatening disease. Currently used induction treatment (cyclophosphamide or rituximab with high-dose corticosteroids) has significantly improved outcome of AAV, but is associated with high toxicity. Alternative complement pathway activation was shown to play a role in the pathogenesis of AAV, thus providing rationale for the use of avacopan, a selective inhibitor of C5a receptor, in the treatment of AAV.

Areas covered: Pharmacokinetic and pharmocodynamic properties of avacopan, clinical efficacy and safety and tolerability of avacopan in so far performed clinical trials in patients with AAV are reviewed and discussed.

Expert opinion: Avacopan was shown to have at least similar efficacy compared to high dose corticosteroids in patients with active AAV with renal involvement, while there were no major safety issues reported. Replacement of corticosteroids should decrease the corticosteroid-related toxicity and improve long-term outcome of patients with AAV even though this still needs to be confirmed in a larger trial. Data on long-term outcome of avacopan-treated patients are currently lacking and will be eagerly awaited. In the future, avacopan could replace corticosteroids not only in the induction phase, but also in the maintenance treatment of AAV.

KEYWORDS:

• ANCA
• vasculitis
• avacopan
• complement inhibition
• treatment

Declaration of interest

V. Tesar was the primary investigator on the CLEAR study, which was funded by Chemocentry. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The authors are supported by a grant from Charles University and General AQ5 University Hospital (PROGRESS).