Glucocorticoid therapy in ANCA Vasculitis - using the Glucocorticoid Toxicity Index as an outcome measure

Abstract

Background
Anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is an autoimmune disease. Induction remission and maintenance treatment typically includes high dose, tapering glucocorticoids (GC) in addition to other immunosuppressive medication. The use of Glucocorticoid Toxicity Index (GTI), provides a global, quantifiable assessment tool in which clinicians can assess GC associated morbidity. Recent trials in AAV have exposed the need for systemic assessment of GC burden. In this small cohort study, we look to address these issues and the justification of newer GC sparing agents such as C5a inhibitors.
Methods
A retrospective cohort study of 43 patients with biopsy AAV was constructed from a single centre between 2012 to 2016 and followed up for 48 months. The GTI table made up of adverse features used to quantify patients GC toxicity. Electronic patient records were reviewed and scores calculated according to published methods. GTI scores were compared with cumulative steroid doses at separate intervals as well as incidences of adverse features in relation to the treatment timeline.
Results
The mean age was 65.9 (± 11.06) years and treatment regimens consisted of glucocorticoids alongside cyclophosphamide or rituximab. Our results showed statistical significance in the association of cumulative GC doses and GTI scores (p=0.008, 95% CI, 1.31 to 8.05). Adverse features relating to mood disturbance and GC induced psychosis occurred early, in contrast
to adrenal insufficiency which typically presented later in the follow up. Infection related adverse events were consistent throughout.
Conclusions
We demonstrated that higher, cumulative doses of steroids in AAV lead to worse glucocorticoid related toxicity. Using the GTI creates potential to individualise and quantify the adverse effects patients experience as a result of GC treatment and permits more patient centred management. Whilst glucocorticoids remain the main adjunctive immunosuppression of AAV treatment, the narrow therapeutic window supports the need for GC-sparing treatments.