Issue: April 2021
Disclosures: Jayne reports consulting fees from AstraZeneca, ChemoCentryx, GlaxoSmithKline and Genentech, as well as grant support paid to the University of Cambridge from GlaxoSmithKline. Please see the study for all other authors’ relevant financial disclosures.
February 18, 2021
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Avacopan outperforms prednisone for ANCA-associated vasculitis remission at 1 year

Issue: April 2021
Disclosures: Jayne reports consulting fees from AstraZeneca, ChemoCentryx, GlaxoSmithKline and Genentech, as well as grant support paid to the University of Cambridge from GlaxoSmithKline. Please see the study for all other authors’ relevant financial disclosures.
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Avacopan is superior to prednisone taper in preventing relapse in patients with antineutrophil cytoplasmic antibody-associated vasculitis at 1 year, and is at least as effective as steroids in controlling the disease at 6 months, according to data.

“High-dose steroids are currently necessary to control the severe inflammation of vasculitis, but their toxicity is a major problem for patients, and they are not always effective,” David R.W. Jayne, MD, FMedSci, of Addenbrooke's Hospital and the University of Cambridge, in the United Kingdom, told Healio Rheumatology. “Complement inhibition with avacopan is a real opportunity to replace steroids with a safer drug that also appears more effective in controlling the disease.”

“Avacopan will offer patients and their physicians an alternative to steroid and the potential for better overall disease control,” David R.W. Jayne, MD, FMedSci, told Healio Rheumatology.

To compare avacopan (CCX168, ChemoCentryx) with a tapering schedule of prednisone among patients with ANCA-associated vasculitis who were being simultaneously treated with immunosuppressive drugs, Jayne and colleagues conducted the ADVOCATE study, a phase 3, randomized controlled trial. A total of 331 participants with ANCA-associated vasculitis were assigned 1:1 to receive 30 mg of oral avacopan twice daily or oral prednisone on a tapering schedule. All participants also received either cyclophosphamide, followed by azathioprine, or rituximab (Rituxan, Genentech).

The researchers used two primary endpoints. The first was remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0, at week 26 with no glucocorticoid use in the previous 4 weeks. The second primary endpoint was sustained remission, defined as remission at both weeks 26 and 52. Both endpoints were analyzed for noninferiority and superiority.

David R.W. Jayne

According to the researchers, who published their findings in the New England Journal of Medicine, the mean BVAS at baseline was 16 in both the avacopan and prednisone groups. Week 26 remission was observed in 72.3% of participants treated with avacopan, and in 70.1% of those in the prednisone group (estimated common difference = 3.4 percentage points; 95% CI, –6 to 12.8). Sustained remission at week 52 was later observed in 65.7% of the avacopan group, and in 54.9% of those who received prednisone (estimated common difference = 12.5 percentage points; 95% CI, 2.6-22.3).

Regarding safety, 37.3% of participants treated with avacopan demonstrated serious adverse events, excluding worsening vasculitis, compared with 39% in the prednisone group.

“The ADVOCATE study demonstrated that avacopan was at least as effective in controlling disease at 6 months as steroids — with all patients receiving an immune suppressive as well — but between 6 and 12 months, and following tapering of steroids, the avacopan group did better through prevention of relapse,” Jayne said. “Secondary endpoints also showed superiority for avacopan with respect to recovery of renal function for those with kidney involvement, in recovery of quality of life, and in fewer side-effects.”

“Avacopan will offer patients and their physicians an alternative to steroid and the potential for better overall disease control,” he added. “This is likely to have long-term benefits for patients in terms of reduced risk of end stage renal failure, reduced risk of steroid induced damage such as osteoporosis and cataracts, and a reduced number of relapse events.”