Prospective study of complications and sequelae of glucocorticoid therapy in ANCA-associated vasculitis

Abstract

Objective Glucocorticoids (GC) are a cornerstone in treating antineutrophil cytoplasmic antibodies-associated vasculitides (AAV), however, they add to morbidity and mortality. To date, GC toxicity in AAV has rarely been systematically investigated. Methods Patients with a confirmed AAV were included in this monocentric prospective study. GC toxicity was assessed by structured interviews, clinical examination and electronic medical record analysis. The Glucocorticoid Toxicity Index (GTI) consisting of the Aggregate Improvement Score (GTI-AIS) and the Cumulative Worsening Score (GTI-CWS) was assessed at two time points (t1 baseline, t2 6 months later). We used regression analyses to assess the relationship between GTI and GC exposure, toxicity, and disease activity, and a receiver operating characteristic analysis to calculate a GC threshold dose beyond which toxicity is expected to occur. Results We included 138 patients with AAV. The median cumulative GC dose was 9014.0 mg. The most frequent adverse events were skin atrophy, osteoporosis and myopathy. GC exposure and toxicity were significantly correlated (p<0.001). GTI-AIS was significantly higher in active disease compared with patients in remission (p<0.001). GTI-CWS scored significantly higher in long-standing diseases (p=0.013) with high cumulative GC doses (p=0.003). Patients with a cumulative GC dose of 935 mg or more showed an 80% likelihood for a clinically meaningful change in GTI scoring. Conclusion The GTI is capable of capturing GC toxicity in AAV and identifies patients at increased risk for GC side effects. Our data support efforts to limit GC exposure in patients with AAV.