Association Between Steroid Therapy and Glucocorticoid Toxicity Studied in Patients With ANCA-Associated Vasculitis

In patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), cumulative doses of steroids result in worse glucocorticoid (GC) toxicity, according to study results published in Kidney 360.

A retrospective cohort of patients with biopsy AAV from a single center between 2012 and 2016 was enrolled in the study and followed up with for 48 months.

A total of 43 patients (mean age, 65.9±11.06 years; 23 women) were included in the analysis of whom all tested positive for ANCA antibodies. Patients received induction treatment with daily oral GCs, along with intravenous cyclophosphamide or rituximab.

At fixed intervals during the 4-year follow-up, the researchers calculated Glucocorticoid Toxicity Index (GTI) and cumulative steroid dose; scores ranged from 0 to 123. At the end of the study, 12 (27.9%) of 37 patients had a GTI score of 0. Except for 1 patient, all of them with a score greater than 60 had received more than 9000 mg of GCs. There was a statistically significant association between cumulative GC dose and GTI score (P =.008; 95% CI, 1.31-8.05).

Glucocorticoid toxicity was observed in 3 (7.0%) patients at 4 weeks; at the end of follow-up, 27 (71.9%) patients had demonstrated toxic effects. The most common adverse effects were infections, reduced bone density, and increasing body mass index. The GC toxicity scores of approximately one-quarter (23.2%) of patients improved during follow-up, a majority of whom had improvements in weight, glucose tolerance, and blood pressure. Toxicity-associated adverse events, such as mood disturbance and steroid-induced psychosis, occurred early during treatment (median time, 21 days [interquartile range (IQR), 18-24 days); however, adrenal insufficiency occurred later in follow-up period (median time, 1059 days [IQR, 895-1224 days]).

Study limitations included the observational nature of the study, with potential confounders including immunosuppressive medications, plasma exchange, and active vasculitis that could have contributed to the development of adverse events. In addition, all scores did not rely on invasive procedures or imaging, and the retrospective nature of the study could have resulted in inaccuracies while reporting mild side effects.

”Using the GTI creates potential to [individualize] and quantify the adverse effects patients experience as a result of GC treatment and permits more patient-[centered] management. Whilst [GCs] remain the main adjunctive immunosuppression of AAV treatment, the narrow therapeutic window supports the need for GC-sparing treatments,” the researchers concluded.

Reference

Floyd L, Morris A, Joshi M, Dhaygude A. Glucocorticoid therapy in ANCA Vasculitis – using the Glucocorticoid Toxicity Index as an outcome measure. Kidney 360. Published online April 20, 2021. doi:10.34067/KID.0000502021