Analysis backs lower-dose GCs for severe ANCA-associated vasculitis


By Selina Wellbelove

3 Apr 2024

Clinicians can be “reassured” that the use of lower dose glucocorticoid treatment in patients with severe ANCA-associated vasculitis can be used without sacrificing long-term-disease control, researchers say.

An international collaboration found that neither the use of plasma exchange (PLEX) or standard glucocorticoid regimen appreciably changed the risk of relapse in a post-hoc analysis of 704 patients who participated in the PEXIVAS trial.

The study, which compared plasma exchange or not with standard and reduced glucocorticoid treatment, found relapse was a common event whichever approach was taken.

Overall, 22.7% of patients experienced relapses, the researchers – including Dr Eswari Vilayur from the John Hunter Hospital, New South Wales, reported in Arthritis and Rheumatology.

The analysis showed a relapse rate of 10.3 relapses per 100 patient-years, and neither PLEX (sub-hazard ratio 0.91 to 0.94, 95% CI 0.66 to 1.31) nor glucocorticoid regimen (sub-hazard ratio 0.93 to 0.94, 95% CIs range from 0.67 to 1.35) “appreciably changed” the rate, they concluded.

However, the data pointed out which patients might be more at risk of relapse, particularly around the identification of proteinase 3-ANCA and the presence of non-haemorrhagic respiratory manifestations at trial entry.

By contrast, receiving dialysis at baseline and the use of cyclophosphamide as induction therapy was associated with a lower risk of relapse, they found.

“These findings add confidence to the recommendations to use the reduced-dose glucocorticoid regimen from PEXIVAS,” the  researchers concluded.

“Additionally, our study provides further understanding of which patients with ANCA-associated vasculitis are at risk of relapse. These data may help predict disease course and inform decision making regarding the choice and duration of maintenance therapy.”

They added that whether or not plasma exchange reduces the risk of kidney failure in this population remains controversial.

However, they noted that any such effect is unlikely to be mediated by preventing renal relapses or exerting a sustained impact on disease activity.

“The reduced-dose glucocorticoid regimen used in PEXIVAS is now commonly recommended due to its lower risk of serious infections than the previous standard-dose regimen.

“The lack of effect on relapses with this dose regimen should reassure clinicians that reducing glucocorticoid exposure during the induction phase does not sacrifice long-term disease control,” the team concluded.

Importantly, the data suggest that it may be possible to accurately predict who is at risk of relapse, which could lead to opportunities for tailored treatments and monitoring, they added.

But more work is needed to validate risk factors and identify accurate risk prediction models incorporating a broader array of information.

‘As by far the largest trial in ANCA associated vasculitis ever performed PEXIVAS is well placed to examine the frequency and impact of disease relapse in patients with this disease who have kidney involvement,” co-author Professor David Jayne, Professor of Clinical Autoimmunity at University of Cambridge, told the limbic, commenting on the trial.

“The headline results that variations in initial therapy with plasma exchange vs no plasma exchange, or standard vs reduced dose glucocorticoids, had no influence on relapse risk is perhaps not surprising as relapses occur over a much longer time course. Of importance was the frequency of relapse, over one-fifth of patients, with potential impacts on kidney and patient survival. This post-hoc study does not change the current recommendations towards use of plasma exchange and reduced dose glucocorticoids for this vasculitis population,” he noted.

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