Avacopan Safety Described in Pooled Vasculitis Trial Data

TOPLINE:

Avacopan treatment for antineutrophil cytoplasmic antibody–associated vasculitis demonstrated lower rates of adverse events, serious adverse events, white blood cell (WBC) count reductions, and infections than standard treatment without avacopan.

METHODOLOGY:

• Researchers pooled data from two phase 2 trials (CLEAR and CLASSIC) and one phase 3 trial (ADVOCATE) that compared avacopan with active control regimens not including avacopan to evaluate the safety of avacopan in patients with granulomatosis with polyangiitis or microscopic polyangiitis.
• They evaluated 439 patients (mean age at screening, 60.2 years; mean disease duration, 22 months; 57.5% men), of whom 239 and 200 received avacopan and control regimens, respectively.
• Patients treated with avacopan had a total exposure of 212.3 patient-years, whereas those receiving the non-avacopan treatment had a total exposure of 195.7 patient-years.
• Exposure-adjusted rates of adverse events, serious adverse events, and adverse events of special interest, including hepatic abnormalities, infections, WBC count reductions, and hypersensitivity events, were analyzed.
• Treatment protocols varied across trials: Patients in CLEAR and ADVOCATE received either no prednisone or lower doses in the intervention than in the control groups, whereas those in CLASSIC received identical prednisone doses across all groups.

TAKEAWAY:

• Exposure-adjusted rates of adverse events per 100 patient-years were significantly lower in the avacopan group than in the control group (difference, −151.9; 95% CI, −218.6 to −85.3).
• The avacopan regimen showed lower rates than the control regimen for serious adverse events (difference, −20.8; 95% CI, −38.3 to −3.3 per 100 patient-years), WBC count reductions (difference, −11.6; 95% CI, −22.0 to −1.2 per 100 patient-years), and infections (difference, −24.3; 95% CI, −48.5 to −0.1 per 100 patient-years).
• Hepatic function abnormalities resulted in serious adverse events in 4.4% of patients in the avacopan group compared with 2.8% of patients in the control group; however, this difference was not statistically significant (difference, 1.7%; 95% CI, −1.8 to 5.1).

IN PRACTICE:

“Avacopan demonstrated a favorable safety profile compared with standard treatment with a prednisone taper. No new safety signals have been identified since avacopan became commercially available, and its safety continues to be closely monitored,” the authors wrote.

SOURCE:

The study was led by Peter A. Merkel, MD, MPH, University of Pennsylvania, Philadelphia. It was published online on April 7, 2025, in ACR Open Rheumatology.

LIMITATIONS:

The differences between trials in glucocorticoid dosing and reported safety outcomes was a major limitation. The phase 2 CLEAR and CLASSIC trials had smaller sample sizes and shorter durations of therapy than the phase 3 ADVOCATE trial.

DISCLOSURES:

The study was supported by ChemoCentryx (a wholly owned subsidiary of Amgen). Some authors reported having financial relationships with Amgen and other pharmaceutical companies, and one author is an employee of Amgen.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.