A study published in The Lancet Rheumatology found that the replacement of a standard prednisone taper with avacopan reduced glucocorticoid toxicity as measured by the Glucocorticoid Toxicity Index (GTI) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Glucocorticoid toxicity is a possible adverse effect of sustained prednisone use. Recently, avacopan, a novel complement C5a receptor inhibitor, has been introduced to treat patients with AAV. If avacopan can replace prednisone, it may reduce the risk of glucocorticoid toxicity among this patient population. 

The GTI is designed to measure glucocorticoid toxicity levels between 2 timepoints and can be used to monitor how a change in medication impacts toxicity. The ADVOCATE trial, a phase 3, randomized, double-blind, double-dummy, active-controlled study that compared avacopan with an oral prednisone taper regimen, used GTI domains to measure changes in glucocorticoid toxicity. 

This study recruited patients with AAV and randomly assigned them in a 1:1 ratio to receive 30 mg of oral avacopan twice daily for 52 weeks and a prednisone-matching placebo for 20 weeks or an oral tapering regimen of prednisone for 20 weeks and an avacopan-matching placebo for 52 weeks. GTI data were collected at baseline, 13 weeks, and 26 weeks. 

Read more about AAV etiology 

The trial included 330 patients—166 received avacopan and 164 received prednisone. The research team reported that participants in the avacopan group demonstrated a substantial reduction in glucocorticoid toxicity according to various GTI domains, although glucocorticoid toxicity remained substantial in both groups. Their findings also suggest that a reduction in glucocorticoid toxicity is desirable not just for safety reasons, but also because it represents a marker of treatment efficacy. 

“Future treatment strategies should therefore strive to reduce glucocorticoid toxicity further in patients with ANCA-associated vasculitis and other inflammatory diseases,” the authors of the study wrote. 


Patel NJ, Jayne DRW, Merkel PA, et al. Glucocorticoid Toxicity Index scores by domain in patients with antineutrophil cytoplasmic antibody-associated vasculitis treated with avacopan versus standard prednisone taper: post-hoc analysis of data from the ADVOCATE trial. Lancet Rheumatol. 2023;5(3):E130-E138. doi:10.1016/S2665-9913(23)00030-9