Reduced-dose glucocorticoids in GPA and MPA increase mortality

In a real-world setting, the reduced-dose glucocorticoids (GC) regimen of the PEXIVAS trial was associated with unfavourable outcomes in patients with severe granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Giving less GCs was associated with an increased risk of death, end-stage kidney disease (ESKD), and progression before achieving remission requiring treatment modification.

Patients with severe GPA and MPA usually receive GCs plus rituximab or cyclophosphamide. In the PEXIVAS trial (NCT00987389), a reduced-dose GC regimen was non-inferior to a standard dose with respect to death or end-stage kidney disease (ESKD), while the infection risk was significantly reduced [1]. However, disease progression or relapse were not among the primary endpoints, and there was a trend towards an increased risk of death or ESKD in participants treated with rituximab. This trial had serious limitations. Therefore, the reduced-dose GC regimen was evaluated in a retrospective, multicentre study [2].

The analysis included 234 patients: 93 with MPA and 148 with GPA. In this cohort, 126 (53.8%) patients received a reduced GC regimen and 108 (46.2%) a standard regimen. The primary endpoint included minor or major relapse, progression before remission requiring treatment modification, ESKD, or death, whichever occurred first.

After 1 year, survival without the occurrence of the primary endpoint was significantly lower in the reduced-dose GC group (P=0.022). The primary endpoint occurred in 62 patients (26.5%): 33.3% in the reduced-dose group versus 18.5% in the standard-dose group (P=0.016). The risk of the primary endpoint was significantly higher in the reduced-dose group (HR 1.72; 95% CI 1.08–2.74). The difference in the risk of death or ESKD (the primary composite outcome in the PEXIVAS trial) was not significant (HR 1.62; 95% CI 0.82-3.19).

The number of patients with a severe infection was also not significantly different between both groups (26 [20.6%] vs 17 [15.7%], respectively; P=0.427). In the reduced-dose GCs group, patients with creatinine levels >300 μmol/L were more likely to meet the primary endpoint (RR 2.14; 95% CI 1.14–4.03). The same was true for patients treated with rituximab (HR 1.61; 95% CI 0.94–2.77).

The authors concluded that vigilance must be increased if the reduced GC regimen is applied, especially in patients receiving rituximab as induction therapy and those with creatinine levels above 300 μmol/L.

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   1. Walsh M, et al. N Engl J Med. 2020;382(7):622-631. doi: 10.1056/NEJMoa1803537.
   2. Nagle S, et al. Real-life Use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis. 0725, ACR Convergence 2023, 10–15 November, San Diego, USA.

 

Medical writing support was provided by Michiel Tent.
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Posted on 1 December 20231 December 2023