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Clinical Trial
. 2025 Oct 5;11(4):e005743.
doi: 10.1136/rmdopen-2025-005743.

Efficacy and safety of avacopan for treatment of patients with ANCA-associated vasculitis receiving cyclophosphamide

Duvuru Geetha  1 , Thomas Neumann  2 , Alexandre Karras  3   4 , Maria C Cid  5 , Peter A Merkel  6 , Sarah Bray  7 , Alana M Bozeman  8 , David R W Jayne  9 ; Members of the ADVOCATE Study Group
Collaborators, Affiliations
Clinical Trial

Efficacy and safety of avacopan for treatment of patients with ANCA-associated vasculitis receiving cyclophosphamide

Duvuru Geetha et al. RMD Open. .

Abstract

Background: This study evaluated the efficacy and safety of avacopan versus a prednisone taper in the subgroup of patients with antineutrophil cytoplasmic antibody-associated vasculitis (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)) receiving cyclophosphamide (CYC) followed by azathioprine (or mycophenolate mofetil) in the ADVOCATE trial.

Methods: Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included glucocorticoid toxicity, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and safety.

Results: Of 330 patients receiving study medication, 116 (35.2%) received CYC (avacopan group, n=59; prednisone taper group, n=57). Remission at week 26 and sustained remission at week 52 were achieved by 37/59 (62.7%) and 33/59 (55.9%) patients in the avacopan group and 34/57 (59.6%) and 30/57 (52.6%) in the prednisone taper group, respectively. Over 52 weeks, relapses were observed in 13.0% in the avacopan group and 22.6% in the prednisone taper group. Improvement in eGFR, speed of albuminuria reduction and differences in glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 55.9% and 56.1% of patients in the avacopan and prednisone taper groups, respectively.

Conclusions: This subgroup analysis of patients who received CYC shows similar rates of remission in the avacopan and prednisone taper groups. Compared with the prednisone taper regimen, the avacopan regimen was associated with a numerically lower relapse rate, greater improvement in eGFR, faster reduction in UACR, lower glucocorticoid-related toxicity and similar overall safety. These results support the use of avacopan in combination with CYC to treat GPA or MPA.

Trial registration number: NCT02994927.

Keywords: Clinical Trial; Cyclophosphamide; Granulomatosis with polyangiitis; Treatment; Vasculitis.

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Conflict of interest statement

Competing interests: DG received consulting fees from Amgen, ChemoCentryx (a wholly owned subsidiary of Amgen), Aurinia, Otsuka, Calliditas, Vera Therapeutics, and GlaxoSmithKline (GSK). TN received consulting fees from GSK AG, AstraZeneca GmbH, Amgen Switzerland AG, and Vifor Pharma Switzerland. AK received consulting fees or honoraria from GSK, Vifor, Novartis, AstraZeneca, and Otsuka. MC received grant/research support from Kiniksa Pharmaceuticals; was a paid instructor for GSK; received payment on Speaker's bureau for GSK and CSL Vifor; received royalties from UpToDate; and was a consultant for CSL Vifor, GSK, AstraZeneca, Alexion, Boehringer Ingelheim, AbbVie, Novartis, and Royalty Pharma. She was supported by Ministerio de Ciencia, Innovación y Universidades/AEI/(PID2023-152265OB-I00)/FEDER-EU). PAM received grant/research support from AbbVie/Abbott, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eicos, Electra, Genentech, GSK, InflaRx, Neutrolis, and Takeda; received consulting fees from AbbVie, Amgen/ChemoCentryx, Argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, CSL Behring, GSK, HiBio, InflaRx, Janssen, Jubilant, Kyverna, Novartis, NS Pharma, Q32, Regeneron, Sanofi, Sparrow, Takeda, and Visterra; holds stock or stock options in Kyverna, Q32, and Sparrow; and received royalties from UpToDate. SB is an employee of Amgen Ltd and owns stock in Amgen Inc. AMB is an employee of Amgen Inc. and owns stock in Amgen Inc. DJ received grant/research support from CSL Vifor; received consulting fees from Alentis, Amgen, AstraZeneca, Chinook, CSL Vifor, GSK, Hansa, and Roche; received honoraria from CSL Vifor; and was a Member of the Board of Aurinia.

Figures

Figure 1
Figure 1. Change from baseline in eGFR in patients with (A) kidney involvement at baseline and (B) kidney involvement and an eGFR <30 mL/min/1.73 m2 at baseline. LS mean and SEM are from mixed-effects models for repeated measures with treatment group, visit and treatment-by-visit interaction as factors and baseline as a covariate. CYC, cyclophosphamide; eGFR, estimated glomerular filtration rate; LS, least squares.
Figure 2
Figure 2. Percentage change from baseline in UACR in patients with albuminuria (≥10 mg/g creatinine) at baseline. Geometric means are from mixed-effects models for repeated measures with the treatment group, visit and treatment-by-visit interaction as factors and baseline as a covariate. Logarithmic transformations were applied to the data before fitting the model. Percent changes from baseline are based on ratios of geometric means of visit over baseline. CYC, cyclophosphamide; LS, least squares; UACR, urinary albumin-to-creatinine ratio.
See this image and copyright information in PMC

References

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