Steroid sparing option for ANCA-associated vasculitis

Wednesday, 24 Feb 2021

The C5a receptor inhibitor avacopan is non-inferior to oral prednisone on a tapering schedule for the management of ANCA-associated vasculitis.

The ADVOCATE trial, published in the NEJM, randomised 331 patients to either oral avacopan (30 mg twice daily) or oral prednisone (tapered from 60 mg/day to none over 21 weeks).

All patients received standard remission-induction therapy with cyclophosphamide (followed by azathioprine) or rituximab. Glucocorticoids were available as rescue therapy to both groups.

The first primary outcome of remission at week 26 was observed in 72.3% of patients in the avacopan group and 70.1% of patients in the prednisone group (p <0.001 for noninferiority; p = 0.24 for superiority).

The second primary end point of sustained remission at week 52 was observed in 65.7% patients in the avacopan group and in 54.9% in the prednisone group (p <0.001 for noninferiority; p = 0.007 for superiority).

The overall incidence of serious adverse events was also similar in the two groups (13.3% v 15.2%). Fatal infections and life-threatening infections were reported in one patient each in the avacopan group and in two patients each in the prednisone group.

The study said quality of life improved in both treatment groups.

While more long term evidence was required, avacopan offered a treatment option that could reduce glucocorticoid-induced toxic effects.

An accompanying editorial called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis.”

“The ADVOCATE trial heralds a change in the treatment of ANCA-associated vasculitis that was previously unthinkable — the possibility of inducing disease remission without glucocorticoids,” the editorial said.

It said glucocorticoids were not only used in the remission-induction phase of severe ANCA-associated vasculitis but are also used to manage minor disease relapses.

“Therefore, it will be of interest to explore whether avacopan could also replace glucocorticoids during management of minor relapses.”

Disclosures: The study was funded by ChemoCentryx. The editorial author Dr Kenneth Warrington reports grants from Eli Lilly, Kiniksa, Roche/Genentech, and GlaxoSmithKline.

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