297. Patients' Use of Glucocorticoids by Source and Time Period in the ADVOCATE Trial of Avacopan

Background: ADVOCATE was a Phase 3, randomized, double-blind, controlled clinical study conducted to provide evidence for the efficacy and safety of avacopan as a treatment for patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. The trial was designed not only to assess the efficacy of avacopan in achieving and sustaining remission, but also to evaluate whether glucocorticoid (GC) use could be safely reduced. This analysis evaluated GC use in the two study groups by source and trial time period. Methods: Patients were randomized to receive prednisone taper or avacopan on a background of either cyclophosphamide (followed by azathioprine) or rituximab. Efficacy endpoints included the percent of patients achieving disease remission at Week 26 and sustained remission at Week 52. The following information regarding GC use was captured in the electronic case report form: type of GC, dose, unit, route, start date, end date, indication for use. GC doses were converted to prednisone-equivalent doses and cumulative GC dose was calculated for each patient for each study period. Results: The avacopan group showed superiority to the prednisone group in sustaining remission at Week 52 (66% vs. 55%; P=0.013). There were 4 sources of GC use in the ADVOCATE study. By far the largest source of GC was the protocol-defined prednisone used in the prednisone group but not the avacopan group, constituting two-thirds of the total GC use in this group (total average dose = 2389 mg), which calculates to an average daily dose of 7.8 mg prednisone. Non-study supplied GC use included: GC as pre-medication with rituximab to reduce hypersensitivity reactions, GC taper over 4 weeks if a patient was on GC at randomization, and GC to treat persistent, worsening, or relapsing vasculitis after week 4. The total mean and median GC doses in both arms of the study are illustrated in Figure 1. During the 52-week treatment period, there was a 63% reduction in the mean GC dose and an 86% reduction in the median GC dose in the avacopan group compared to the prednisone group. Most patient-incidence use of GC occurred within the first 4 weeks of the study and was similar between treatment groups. After Week 4, the incidence of non-study supplied GC use dropped substantially and from Week 26 to 52, there was a lower incidence of extra GC use in the avacopan group (27%) compared to the prednisone group (39%). Conclusions: Given that to date it is not acceptable or feasible to conduct a clinical trial of patients with moderate-severe ANCA-associated vasculitis without allowing GC use, the information presented offers important considerations in the design and implementation of future clinical trials in ANCA-associated vasculitis. In the ADVOCATE trial, the avacopan group had an overall mean reduction of approximately 2500 mg of prednisone-equivalent GC compared to the prednisone group. These data demonstrate the substantial “glucocorticoid-sparing” effect of using avacopan to treat ANCA-associated vasculitis according to the treatment regimen used in the ADVOVATE trial. Disclosures: Peter A. Merkel reports receiving consulting and research support from AbbVie, AstraZeneca, Boeringher-Ingelheim, Bristol-Myers Squibb, ChemoCentryx, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Takeda; consulting fees from CSL Behring, Dynacure, EMDSerono, Jannsen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, Pfizer, Sparrow, Talaris; royalties from UpToDate. David R.W. Jayne reports receiving consulting fees from AstraZeneca, ChemoCentryx, and Genentech and grant support, paid to the University of Cambridge, and consulting fees from GlaxoSmith-Kline. Pirow Bekker reports receiving consulting fees from and owning stock and stock options in ChemoCentry