Initial high-dose corticosteroids and renal impairment are risk factors for early severe infections in elderly patients with antineutrophil cytoplasmic autoantibody-associated vasculitis

Abstract

Recent large observational studies of antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) show that severe infection is a major cause of death and that the majority of infections occur during the early phase of initiating remission-induction therapy. Many risk factors for severe infection have been suggested, but these have been inconsistent. Nevertheless, infectious risk factors in elderly patients with AAV have not been adequately investigated in previous studies. In this retrospective observational study, we examined potential predictors of severe infection within 90 days (early severe infections) after remission-induction therapy in patients with AAV aged 65 years or older. We included 167 consecutive elderly patients with AAV admitted to our hospital. Data from medical history and remission-induction therapy were analyzed for predictive risk factors associated with early severe infections. The relationship between initial doses of corticosteroids and cumulative incidence of severe infections was also analyzed. A multivariate analysis of risk factors for early severe infections was performed using logistic regression analysis. The Kaplan–Meier method was used to estimate the overall survival, and the log-rank test was used to evaluate the differences between patients with and without early severe infections. Gray method was used to compare the cumulative incidence of severe infections in patients who did and did not receive initial high-dose corticosteroids. Logistic regression analysis showed that initial high-dose corticosteroid administration (prednisolone ≥0.8 mg/kg/d) (odds ratio [OR] 3.86, P = .030) and serum creatinine levels at diagnosis ≥1.5 mg/dL (OR 5.13, P = .003) were independent predictors of early severe infection although administration of cyclophosphamide or rituximab was not. The cumulative incidence of severe infections was also significantly higher in patients who received initial high-dose corticosteroids (P = .042), and patients with early severe infections exhibited a high mortality rate within 6 months (P < .001). Our findings suggest that initial high-dose corticosteroids and renal impairment at diagnosis are associated with a higher risk of early severe infections and early death in elderly patients with AAV.

Glucocorticoid-free treatment of severe ANCA-associated vasculitis

“…High-dose glucocorticoids may actually be the major contributor to adverse events in these patients [11]. Indeed, a recent study found that initial high-dose glucocorticoid exposure (and not the use of cyclophosphamide or rituximab) was a major risk factor for severe infection in elderly patients (defined in this study as >65 years old) with AAV [12]. Advanced age and frailty are two key factors that drove our decision to completely avoid glucocorticoid treatment.…”

Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis

“…Indeed, retrospective studies have shown that high-dose intravenous glucocorticoid use is associated with more frequent infections in patients with AAV, particularly in the elderly and those with severe disease features 26,27 . We highlight that intravenous glucocorticoid use was low in our study (median dose for entire cohort 0.25 [0-0.5] g), significantly less than the 1-3 received in recent controlled studies such as PEXIVAS.…”

COVID-19 and Rheumatic Diseases: It Is Time to Better Understand This Association

“…Evidence arising from larger cohorts of patients with IMRD has associated the chronic use of GC with worse COVID-19 outcomes 13,16,17,18 . Patients with IMRD treated with high-dose CS are at significant risk of other serious infections 19 . In addition to this higher susceptibility, these patients can potentially develop a more severe course of infection due to the variety of metabolic and cardiovascular complications related to cortisol excess 20 .…”