Summary
A 2026 readjudication of the 330-person ADVOCATE trial found avacopan produced remission rates similar to a prednisone taper in granulomatosis with polyangiitis and microscopic polyangiitis. The preprint also reports lower glucocorticoid exposure and toxicity with avacopan.
A 2026 readjudication of the ADVOCATE trial found that avacopan produced remission rates similar to a prednisone taper in people with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The medRxiv preprint, posted on September 16, 2026, reports that the avacopan treatment strategy also reduced glucocorticoid exposure and toxicity.
GPA and MPA are forms of ANCA-associated vasculitis, a group of autoimmune diseases in which inflammation damages blood vessels and can affect multiple organs. The updated analysis revisited the trial’s primary outcomes after concerns about the adjudication procedures used for nine participants in the original 2019 analysis.
What was readjudicated?
The ADVOCATE trial enrolled 330 participants and randomly assigned them in a 1:1 ratio to either avacopan or a prednisone taper. The avacopan dose was 30 mg twice daily. Participants in both treatment groups also received either cyclophosphamide or rituximab.
An independent, blinded committee reassessed the primary outcomes for all participants. These outcomes were remission at week 26 and sustained remission at week 52. The study prespecified noninferiority if the lower bound of the 95% confidence interval for the difference between groups was above −20.0 percentage points. Superiority required that the lower bound be above 0 percentage points.
This was a readjudication of the existing phase 3 clinical trial registered as NCT02994927, rather than a new treatment trial with newly enrolled participants.
Remission results at weeks 26 and 52
| Outcome | Avacopan | Prednisone taper | Adjusted difference, 95% CI |
|---|---|---|---|
| Remission at week 26 | 68.1% | 67.1% | 2.2 percentage points (−7.5 to 11.9) |
| Sustained remission at week 52 | 61.4% | 52.4% | 9.8 percentage points (−0.3 to 19.9) |
The week-26 result met the study’s noninferiority criterion because the confidence interval’s lower bound, −7.5 percentage points, was above −20.0. The week-52 result also met the noninferiority criterion, with a lower bound of −0.3 percentage points.
The numerical difference at week 52 favoured avacopan, but the confidence interval extended slightly below zero. Under the prespecified analysis plan, this meant the result did not meet the threshold for superiority. The readjudicated findings therefore support similarly high remission and sustained-remission rates, rather than establishing that avacopan was superior to prednisone on these primary outcomes.
The updated values were somewhat lower than those reported in the 2019 adjudication. In that earlier analysis, remission at week 26 was recorded in 72.3% of the avacopan group and 70.1% of the prednisone group, while sustained remission at week 52 was recorded in 65.7% and 54.9%, respectively. The adjusted differences were 3.4 percentage points at week 26 and 12.5 percentage points at week 52.
What the findings mean for steroid exposure
Prednisone is a glucocorticoid, or corticosteroid, commonly used to suppress the inflammation caused by autoimmune disease. Glucocorticoid treatment can be effective but may cause toxicity, particularly when exposure is substantial or prolonged. A treatment approach that maintains disease control with less exposure to these medicines could therefore be clinically meaningful.
The preprint reports that secondary endpoints favoured avacopan, including measures of glucocorticoid exposure and toxicity, kidney parameters, health-related quality of life and safety. The supplied abstract does not provide numerical estimates for each of those secondary outcomes, so the clearest quantified result is the similarity in remission rates between the two treatment strategies.
The authors’ conclusion concerns avacopan used together with rituximab or cyclophosphamide. It does not describe avacopan as a standalone replacement for the other immunosuppressive treatments used in the trial.
How to read the updated evidence
The evidence comes from a randomized human clinical trial and a blinded readjudication of its primary outcomes. The new analysis was prompted by concerns about the earlier adjudication, making the change in results itself important when interpreting the trial’s history.
The report is a medRxiv preprint and has not yet undergone the peer-review process associated with a journal publication. Amgen funded the work; the source states that three authors are Amgen employees who hold company stock, while other authors report consulting, research or other industry relationships. The underlying analysis data are not publicly available, although qualified researchers may request access subject to review and governance requirements.
Taken together, the readjudicated results indicate that avacopan achieved remission outcomes comparable to a prednisone taper in GPA and MPA while the study authors report lower glucocorticoid exposure and toxicity. The strongest quantitative conclusion is noninferiority on remission outcomes; the available abstract does not establish superiority.