Evaluation of the Long-Term Safety of Avacopan in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in the Real World (AvacoStar): Protocol for a Noninterventional Prospective Cohort Study.

Background: Established treatments for granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) include the use of immunosuppressive agents for remission induction followed by maintenance therapy. However, patients continue to experience disease progression, organ damage, and adverse events related to current therapies. Avacopan, an oral selective C5a receptor antagonist, was approved by the European Commission in January 2022 for the treatment of adult patients with severe, active GPA or MPA in combination with rituximab (RTX) or cyclophosphamide (CYC). In the pivotal phase 3 ADVOCATE (Avacopan Development in Vasculitis to Obtain Corticosteroid Elimination and Therapeutic Efficacy) study, avacopan was noninferior to prednisone taper in achieving remission at week 26 and superior in sustaining remission at week 52; furthermore, a greater improvement in estimated glomerular filtration rate with avacopan was also observed at week 52. The AvacoStar study will generate data on the benefit and risk and safety profile of avacopan in patients in a real-world context, including in those where treatment may potentially continue beyond 1 year. Objective: The primary objective of AvacoStar is to evaluate the incidence of defined medical events of special interest in patients with antineutrophil cytoplasmic antibody-associated vasculitis commencing avacopan. These include liver injury, cardiac safety, serious infections, and malignancy. Methods: AvacoStar is a noninterventional, multinational, prospective postauthorization safety study. It will enroll up to 500 patients in Germany and the United Kingdom in 2 groups of approximately 250 participants each: those treated with avacopan (plus a standard of care at local investigators' discretion; usually an RTX- or CYC-based regimen) and a second cohort treated with a CYC- or RTX-based induction regimen without avacopan. Avacopan and the standard of care will be prescribed in the usual manner in accordance with the corresponding summary of product characteristics under the sole decision of the investigator. The treatment decision will fall within current established practice. Eligible participants will be aged ≥18 years with severe, active GPA or MPA as determined by the investigator at the time of commencing avacopan or non-avacopan standard-of-care induction therapy. Patients will be followed for up to 7 years. Results: This study has been enrolling patients since September 11, 2023. The final report is expected in the second half of 2031; interim reports are planned every 24 months after the first patient first visit. Conclusions: The AvacoStar study will be the largest European prospective real-world evidence comparative study conducted to date that evaluates the long-term safety of avacopan in severe, active GPA or MPA. This study is expected to yield important insights on the use of avacopan in severe, active GPA or MPA in a real-world setting.