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Glucocorticoids Induced Adverse Events in Patients with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Are Frequent and Often Severe, but Under-Reported: A Systematic Review

Abstract

Tejas Thomas*, Dieter Götte, Bernhard Hellmich, Duvuru Geetha, Peter Antony Rutherford, Kumari Priyanka

Background: Glucocorticoids are cornerstone for treatment of anti-neutrophil cytoplasmic Antibody-Associated Vasculitis (AAV) but
their significant dose-dependent toxicity is a major concern in clinical practice. This systematic review aims to determine the frequency
and proportion of glucocorticoid-related adverse events in patients with AAV.
Method: A systematic literature search was performed in the Embase, Medline and PubMed databases with limitation on years of publication
between January 2000 and December 2020. Full text articles from randomized controlled trials, other interventional and observational
studies including data on the study design, population size, drugs administered and adverse events reported were considered for the
analyses. Studies focused exclusively on eosinophilic granulomatosis with polyangiitis were excluded. A regression model was run to
explore the relationship between mean doses of glucocorticoids, duration and reported adverse events. Furthermore, a correlation matrix
was generated to analyse the rate of incidence of adverse events.
Results: A total of 91 articles were reviewed. Most frequently reported serious adverse events included death (12%) and severe infections
(9%) while non-serious adverse events included infections (not specified) and leukocytopenia (approximately 14%each). Diabetes was
frequently reported according to the Vasculitis Damage Index components. Regression analysis revealed a significant association between
duration of glucocorticoid treatment and occurrence of infections and eye disorders (not specified, p<0.05). There was no significant
association between the mean glucocorticoid dose and occurrence of reported adverse events.
Conclusion: The increasing clinical burden of glucocorticoid-related adverse events in patients with AAV could be reduced by considering
advanced therapeutic strategies.

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