ANCA-ASSOCIATED VASCULITIS TREATED WITH AVACOPAN VERSUS A STANDARD PREDNISONE TAPER: GLUCOCORTICOID TOXICITY INDEX SCORES BY DOMAIN
Authors: Naomi Patel et al.
The ADVOCATE trial was a RCT comparing avacopan vs prednisone in addition to standard care in ANCA-associated vasculitis (AAV). The Glucocorticoid Toxicity Index (GTI), a composite score, measures change in GC toxicity. Data from the GTI domains provide a Cumulative Worsening Score (CWS) and an Aggregate Improvement Score (AIS). This analysis evaluates scores from the 8 GTI domains in ADVOCATE: Body Mass Index, Glucose Tolerance, Lipid Metabolism, Blood Pressure, GC Myopathy, Skin, Neuropsychiatric, and Infection.
The total mean (median) GC use during the first 26 weeks was 1,073 mg (400 mg) in the avacopan group, and 3,193 mg (2,847 mg) in the prednisone group. At week 26, the distribution of scores in the Body Mass Index (P=0.02), Lipid Metabolism (P< 0.01), and Skin (P=0.02) domains all significantly favored the avacopan group. GC Myopathy and Infection showed favorable trends at 26 weeks (P=0.06 and P=0.07, respectively). Glucose Tolerance domain CWS values were lower in the avacopan group at both 13 and 26 weeks and were statistically significant at 13 weeks (P< 0.01). For the AIS domains, Body Mass Index, Lipid Metabolism, and Skin were all lower in the avacopan group at both 13 and 26 weeks.
This study confirms the substantial reduction in GC toxicity associated with replacing a standard prednisone tapering schedule with avacopan in the treatment of AAV. The data demonstrate that the benefits were experienced across multiple domains of toxicity, emphasizing the value of a composite measure that quantifies GC toxicity directly, assessing both cumulative toxicity and aggregate change. Taken together the data argue for the use of avacopan in case of elevated GC risks such as osteoporosis, cardio-vascular diseases, diabetes mellitus