26 February 2020

Trial supports cuts to glucocorticoid dose

Corticosteroids

The PEXIVAS trial has already changed practice, with nephrologists now confidently halving the prednisolone prescription for patients with severe ANCA-associated vasculitis.

The trial randomly allocated around 700 patients with severe ANCA-associated vasculitis to receive either a normal or reduced dose of oral glucocorticoids.

At six months, the reduced-dose group had 60% less cumulative dose of glucocorticoids than the standard-dose group.

The trial tracked patients with severe ANCA-associated vasculitis who had either poor kidney function or diffuse pulmonary haemorrhage over an average of three years.

Serious infections were less common in the reduced-dose group than the standard-dose group at one year, but other adverse event rates were similar among the two groups.

“The results of the glucocorticoid arm of the study are very pleasing,” said Professor Richard Kitching, a nephrologist at Monash University and Monash Health, the head of the Monash Vasculitis Clinic and the chair of the ANZ Vasculitis Society.

“To be confidently able to prescribe half as much prednisolone for patients is a huge advantage and this has improved standard of care.

“Without proper induction treatment outcomes are poor, but the side-effects of the high dose prednisolone for patients are often critically important. They can cause severe morbidity and markedly impact people’s quality of life.”

The PEXIVAS trial was the largest ever in ANCA-associated vasculitis and it had already changed practice in Australia and New Zealand, Professor Kitching said.

The trial results, published in NEJM in February, have been presented and discussed at nephrology and rheumatology conferences in Europe, the US and Australia.

“One of the key practice changes to come out of this is that reduced dose glucocorticoid
was non-inferior to standard dose glucocorticoid for the primary outcome of end-stage kidney disease/death and sustained remission,” said Professor Catherine Hill, the director of the rheumatology unit at The Queen Elizabeth Hospital in and a clinical professor at the University of Adelaide.

“We should feel more comfortable using a reduced dose glucocorticoid regimen, especially with reduced infection; although there were a few more renal adverse effects in the low dose group.”

The PEXIVAS trial also examined the role of plasma exchange in treatment by randomising patients to either receive plasma exchange or not.

There is still a lot of uncertainty around whether this quite invasive treatment should be a routine part of therapy for people with severe disease, said Professor Kitching.

There had been two meta-analyses on plasma exchange; one concluded that the treatment had benefits, the other did not, he said.

The PEXIVAS trial was quite large and showed that plasma exchange conferred little benefit.

However, there might still be a case for treatment in isolated specific cases, Professor Kitching said.

“The findings indicate that plasma exchange should not be used in most patients with ANCA-associated vasculitis who have severe kidney dysfunction,” US nephrologists Dr Vimal Derebail and Dr Ronald Falk wrote in an accompanying editorial.

However, plasma exchange “may benefit carefully selected subgroups of patients”, such as those with concomitant anti–glomerular basement membrane disease or those with rapidly progressive glomerulonephritis but minimal scarring, the nephrologists said.

“In our judgment, until a study specifically designed to evaluate efficacy in patients with pulmonary haemorrhage has been performed, plasma exchange should remain part of the induction regimen for patients with ANCA-induced pulmonary haemorrhage,” they said.

NEJM, 13 February
doi: 10.1056/NEJMoa1803537

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