REAL-LIFE USE OF THE PEXIVAS REDUCED-DOSE GLUCOCORTICOID REGIMEN IN GRANULOMATOSIS WITH POLYANGIITIS AND MICROSCOPIC POLYANGIITIS
Authors: Benjamin Terrier et al.
Glucocorticoids (GCs) in combination with rituximab (RTX) or cyclophosphamide are the cornerstone of treatment for patients with severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The PEXIVAS trial did not show a benefit of plasmapheresis but demonstrated non-inferiority of reduced-dose GC regimen compared to standard dose for the incidence of death or end-stage kidney disease (ESKD), with a significant reduction in serious infections at one year.
This retrospective multicenter study compared the PEXIVAS reduced-dose GC regimen with a standard regimen in patients with severe GPA or MPA flare between January 2018 and April 2022. The primary composite endpoint included the occurrence of death, ESKD, progression before remission requiring treatment modification or relapse.
Of the 234 patients enrolled (93 MPA and 148 GPA), 126 (53.8%) received a reduced GC regimen and 108 (46.2%) received a standard regimen. The primary endpoint occurred in 62/234 (26.5%) of patients during the first year of follow-up: 33.3% of patients on the reduced dose versus 18.5% on the standard dose (p=0.016). In the multivariate analysis, a reduced GC regimen was significantly associated with the occurrence of the endpoint compared to a standard regimen (HR 1.72; 95%CI 1.08-2.74), but was not associated with an increased risk of death or ESKD (HR 1.62; 95%CI 0.82-3.19). There was no significant difference in serious infections at 1 year (20.6% vs 15.7%, p=0.427).
In sharp contrast to the findings of the PEXIVAS study, this large French cohort documents an impressive difference in outcome in standard versus reduced GC dose to treat relapsing MPA and GPA. Together the available data suggest a differential approach: In case of first diagnosis and normal kidney function, the reduced dose regimen may be chosen, however, in case of relapse with reduced kidney function the standard dose appears to be appropriate. Furthermore, the data argue for a steroid-sparing strategy such as prescription of avacopan.