The following is a summary of “Glucocorticoid Toxicity Index-Metabolic Domains, an abridged version of the Glucocorticoid Toxicity Index: post-hoc analysis of data from the ADVOCATE trial,” published in the July 2023 issue of Rheumatology by Patel et al.
It is essential to quantify glucocorticoid toxicity to reduce it. Effectively measuring toxicity in clinical trials, the Glucocorticoid Toxicity Index (GTI) calculates two scores: the cumulative worsening score (CWS) and the aggregate improvement score (AIS). In clinical practice, however, the volume of patients limits the time available for standardized assessments. Researchers aimed to compare the GTI with a shortened version of the GTI, the GTI-Metabolic Domains (GTI-MD), which could aid in addressing this issue by utilizing data readily collected during routine visits and do not require additional effort from clinicians. ADVOCATE was a randomized, double-masked, double-dummy, phase 3 trial in which avacopan replaced the standard prednisone decline in patients with antineutrophil cytoplasmic antibody-associated vasculitis. They calculated the cumulative worsening score (CWS) and aggregate improvement score (AIS) for each domain of the GTI-MD, which includes the BMI, glucose tolerance, blood pressure, and lipid metabolism domains of the GTI, to assess its ability to distinguish between the avacopan and prednisone groups about glucocorticoid toxicity.
The validation set consisted of data from two additional disease cohorts, one consisting of asthma patients and the other of patients with cutaneous autoimmune disease. At week 13, complete data were available for 321 (97%) of the 330 participants in the ADVOCATE trial’s intention-to-treat population. At week 26, data from these individuals were included in their post-hoc analysis. In ADVOCATE, 98 (59%) of 166 participants in the avacopan group were men, and 68 (41%) were women, while 88 (54%) of 164 participants in the prednisone group were men and 76 (46%) were women; the average age of participants was 61·2 years [SD 14·6] in the avacopan group and 60·5 years [SD 14·5] in the prednisone group. About 159 patients comprised the validation cohort (89 with glucocorticoid-dependent asthma, of which 40 [45%] were men, 49 [55%] were women, and 70 with the autoimmune blistering disease of the skin, of which 30 [43%] were men, and 40 [55%] were women). The Spearman’s rank correlation coefficient in ADVOCATE between the GTI-MD CWS and the GTI CWS for the combined treatment groups was 0.78 (95% CI: 0.75–0.81; P<0.0001).
The correlation coefficient for the AIS was 0.73 (0.69–0.77, P<0.0001). The GTI-MD distinguished the groups based on glucocorticoid toxicity at 13 and 26 weeks. The mean GTI-MD CWS was less toxic in the avacopan group than in the prednisone group (15·9 vs. 23·0 at 13 weeks [P=0·0010]; 26·7 vs. 31·7 at 26 weeks [P=0·0092]). The GTI-MD AIS values were also indicative of less toxicity in the avacopan group (2·5 versus 13·0 at 13 weeks [P=0·0003] and 4·4 versus 10·1 at 26 weeks [P=0·027]). A GTI-MD score of 0 indicated a low probability of toxicity in the remaining GTI domains. In the validation set, the correlation between the GTI-MD CWS and the GTI CWS was 0.61 (95% CI: 0·50–0·70; P<0·0001), and the correlation between the AIS and the GTI-MD CWS was 0.58 (0.47–0.68) (P<0·0001). The GTI-MD correlates well with the complete GTI and could be easily integrated into routine clinic workflows without additional clinician input. Using the GTI-MD in the background of electronic medical records systems could assist clinicians in longitudinally monitoring glucocorticoid toxicity to prevent the burden of chronic, treatment-related harms and reduce long-term health system costs.