The following is a summary of the “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,” published in the March 2023 issue of Rheumatology by Patel, et al.

The Glucocorticoid Toxicity Index (GTI) was used to quantify glucocorticoid toxicity change in the ADVOCATE trial, which compared the complement C5a receptor inhibitor avacopan to a standard prednisone taper in patients with antineutrophil cytoplasmic antibody-associated vasculitis. To better differentiate treatment groups, they conducted a post hoc analysis of the ADVOCATE data to examine how different GTI domains were affected over time. In patients with ANCA-associated vasculitis, the ADVOCATE trial compared the effects of oral avacopan (30 mg twice daily for 52 weeks) plus a prednisone-matching placebo for 20 weeks with the effects of oral prednisone tapered over 20 weeks plus a prednisone-matching placebo for 52 weeks. Weight, height, blood pressure, glucose tolerance, lipid metabolism, glucocorticoid myopathy, skin toxicity, neuropsychiatric effects, and infection data were collected at baseline, 13 weeks, and 26 weeks via the GTI. 

As part of this post hoc analysis, they determined the cumulative worsening score (CWS) and aggregate improvement score (AIS) for each GTI domain, evaluated the relative importance of each domain to the overall GTI score, and identified the domains that best distinguished the avacopan and prednisone groups. Mantel-Haenszel 2 tests were used to compare the groups’ differences in domain scores. At week 13, 321 (97%) of the 330 patients included in the ADVOCATE trial’s intention-to-treat population had complete data (160 in the avacopan group, and 161 in the prednisone group), and at week 26, 307 (93%) of the 330 patients had complete data (154 in the avacopan group, and 153 in the prednisone group) and were evaluated. In ADVOCATE, the mean age was 61 (612 years [SD 146] in the avacopan group and 605 years [145] in the prednisone group); 98 (59%) of the 166 patients in the avacopan group and 68 (41%) were women; 88 (54%) of the 164 patients in the prednisone group and 76 (46%) were women. Out of a total of 330 patients, 278 (84%). Avacopan patients used less glucocorticoids than prednisone patients over a 26 week period (1,073 mg [SD 1669] vs 3192 mg [1174]).

The CWS and AIS showed that by week 13, the avacopan group had significantly less glucocorticoid toxicity than the prednisone group had in four domains of the GTI (body mass index, glucose tolerance, lipid metabolism, and skin toxicity). At 26 weeks, the avacopan group had significantly lower CWS values in the body mass index (BMI), lipid metabolism (lipids), and skin toxicity (toxicity) domains than the prednisone group did. In order to lessen the toxicity of glucocorticoids, the prednisone group was not favoured by any domain. At 26 weeks, glucocorticoid toxicity affected 280 (30%) of 307 patients. The greatest influences on CWS values at 26 weeks were blood pressure (35% in the avacopan group versus 25% in the prednisone group), infection (22% versus 24%), and lipid metabolism (20% versus 15%). At the 26-week mark, 128 (42%) of 307 patients showed both improvement and worsening across multiple dimensions. By substituting an avacopan taper for the conventional prednisone taper, glucocorticoid toxicity in several GTI domains was reduced in patients with ANCA-associated vasculitis. Glucocorticoid toxicity was often complex, with patients showing improvement in some areas while worsening in others. These results highlight the need for a composite measure of glucocorticoid toxicity that can quantify cumulative deterioration and aggregate change directly.

Source: sciencedirect.com/science/article/abs/pii/S2665991323000309