‘Increased vigilance’ necessary when reducing glucocorticoid dose in ANCA vasculitis
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SAN DIEGO — Patients with granulomatosis with polyangiitis and microscopic polyangiitis who lower their glucocorticoid dose have an increased risk for death, renal failure, progression or relapse, said a presenter at ACR Convergence 2023.
“As you know, glucocorticoids with rituximab [Rituxan, Genentech] or cyclophosphamide are the cornerstone of treatment for ANCA-associated vasculitis,” Sophie Nagle, MD, of AP-HP Cochin Hospital, in Paris, told attendees. “There are associations between shorter duration of glucocorticoids and a higher number or relapses.”
However, Nagle also acknowledged that glucocorticoids are associated with “potentially fatal” adverse events.
She added that patients with severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are commonly treated with glucocorticoids and rituximab.
To assess efficacy and safety of the reduced dose of glucocorticoids, in a real-world setting, among this patient population, Nagle and colleagues conducted a retrospective, multicenter analysis of the PEXIVAS trial. This trial had demonstrated that reducing glucocorticoid doses was non-inferior to standard dosing in mitigating end-stage kidney disease (ESKD) or mortality risk in these patients. However, the study failed to include endpoints pertaining to disease progression or relapse, according to Nagle. In addition, subgroup analysis revealed a trend toward ESKD or mortality risk associated with rituximab, she said.
The current analysis included 234 patients from 19 centers in France, of whom 148 had GPA and 93 had MPA. Eligible participants experienced a flare between January 2018 and June 2022. A composite of death, ESKD, progression before remission requiring intervention or relapse served as the primary endpoint. Baseline data showed that 126 patients received a reduced glucocorticoid regimen while 108 were treated with standard of care.
“The kidney was the most frequent organ involved, in 70%,” Nagle said. “Kidney disease was severe.”
According to the researchers, the primary endpoint occurred in 26.5% of patients overall during the first year of follow-up. This outcome was reported in 33.3% of patients in the reduced dose compared with 18.5% of those in the standard dose arm (P = .016). Multivariable analysis results showed that a reduced glucocorticoid regimen carried a significant association with the primary endpoint compared with standard of care (HR = 1.72; 95% CI, 1.08-2.74).
“The primary outcome occurred more frequently in the reduced dose group compared with the standard dose group,” Nagle said.
However, the reduced dose failed to increase specific components of the primary endpoint, including mortality or ESKD risk (HR = 1.62; 95% CI, 0.82-3.19). In addition, serious infection rates were comparable between the two groups, with incidence rates of 20.6% for the reduced dose group and 15.7% for standard dosing (P = .427).
“There was no significant difference between the two groups like in the PEXIVAS trial,” Nagle said.
Propensity score matching analysis demonstrated a trend toward meeting the primary endpoint in the reduced-dose arm (HR = 1.57; 95% CI, 0.93-2.64). Subgroup analysis of the reduced-dose arm showed that patients with creatinine levels greater than 300 mol/L were more likely to meet the primary endpoint (RR = 2.14; 95% CI, 1.14-4.03), according to the researchers.
Among patients treated with rituximab, the reduced-dose glucocorticoid regimen was associated with the primary endpoint (HR = 1.61; 95% CI, 0.94-2.77). In addition, rituximab-treated patients in the reduced glucocorticoid group also were more likely to experience death or ESKD (HR = 2.42; 95% CI, 1.04-5.66).
“In a real-world setting, the reduced-dose glucocorticoid regimen of PEXIVAS was significantly associated with an increased risk for death, ESKD, progression before remission or relapse compared to patients receiving a standard-dose glucocorticoid regimen,” Nagle said. “The PEXIVAS reduced-dose glucocorticoid regimen was not associated with an increased risk for death or end-stage kidney disease, nor with the occurrence of severe infections at 1 year.”
In this context, Nagle offered recommendations for clinicians managing this patient population.
“Increased vigilance is required when using the reduced-dose glucocorticoid regimen, especially in two subgroups, due to risk of failure,” she said.
These two groups include patients being treated with rituximab induction therapy and those with severe kidney disease at baseline.
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Nagle S, et al. Abstract 725. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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