The results of PEXIVAS have finally been published in the NEJM. The long-awaited trial sought to put to bed the question over the use of plasma exchange (PEX) for ANCA associated vasculitis (AAV). 704 patients were randomised in a 2-by-2 factorial design to test both the use of plasma exchange and two dosing regimens for glucocorticoids (GC), standard-dose and reduced-dose. The primary outcome was a composite of death or ESKD. The headline result was that there was no difference between plasma exchange and no-plasma exchange in terms of the primary outcome, see figure below. A sub-group analysis showed no benefit in any of the pre-specified groups, although the HR was 0.64 for those with alveolar haemorrhage.
The results of the steroid part of the study are interesting and will probably change current practice. The reduced dosing regimen was non-inferior to standard dosing with respect to the primary outcome. The standard and reduced GC groups received the same amount of prednisolone in the first week but thereafter the dose was rapidly scaled back for the reduced dose group, see table below for the exact dosing. The absolute difference between the steroid groups was 2.3% (90% CI, -3.4 to 8) which met the criterion for non-inferiority of 11%. What’s more, there were significantly less serious infections at 1 year in the reduced dose group, HR 0.69 (95% CI, 0.52-0.93). There were more “kidney/urinary” events in the reduced dose regime, 50 vs 27 (RR 1.84, CI 1.18 to 2.87). I asked the first author of the study, Dr Mike Walsh, what constituted these events and this was his response: “Hodge podge. Low overall numbers but quite a few extra dialysis access hospitalizations”. However, there was no difference in the number of patients in the low or standard GC dosing groups reaching ESKD.
The results of this trail were first announced at UK Kidney Week in 2018. Although negative for plasma exchange the feeling at the time was that there may still be a role for PEX in some cases. The mood does seem to have changed somewhat since then. When the results were discussed on #NEPHJC recently, there was seemingly broad consensus that most would refrain from using PEX in future cases, although, in cases of alveolar haemorrhage there were still those arguing that it may still have a role. The trial is another resounding success for minimising steroids. As with the recently published MinTac trial there is now further evidence that we can safely reduce the use of steroids in renal conditions, leading to a reduction in the number of infections in our patients.
So is the death knell of plasma exchange in AAV? Maybe, certainly it’s hard to justify its use in most cases now, although, I suspect many will still find it hard to resist in cases of severe alveolar haemorrhage.
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