RETRACTED: Avacopan for the Treatment of ANCA-Associated Vasculitis
Open accessAbstract
BACKGROUND: The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: In this randomized, controlled trial, we assigned patients with ANCA-associated vasculitis in a 1:1 ratio to receive oral avacopan at a dose of 30 mg twice daily or oral prednisone on a tapering schedule. All the patients received either cyclophosphamide (followed by azathioprine) or rituximab. The first primary end point was remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 (on a scale from 0 to 63, with higher scores indicating greater disease activity) at week 26 and no glucocorticoid use in the previous 4 weeks. The second primary end point was sustained remission, defined as remission at both weeks 26 and 52. Both end points were tested for noninferiority (by a margin of 20 percentage points) and for superiority. RESULTS: A total of 331 patients underwent randomization; 166 were assigned to receive avacopan, and 165 were assigned to receive prednisone. The mean BVAS at baseline was 16 in both groups. Remission at week 26 (the first primary end point) was observed in 120 of 166 patients (72.3%) receiving avacopan and in 115 of 164 patients (70.1%) receiving prednisone (estimated common difference, 3.4 percentage points; 95% confidence interval [CI], -6.0 to 12.8; P<0.001 for noninferiority; P = 0.24 for superiority). Sustained remission at week 52 (the second primary end point) was observed in 109 of 166 patients (65.7%) receiving avacopan and in 90 of 164 patients (54.9%) receiving prednisone (estimated common difference, 12.5 percentage points; 95% CI, 2.6 to 22.3; P<0.001 for noninferiority; P = 0.007 for superiority). Serious adverse events (excluding worsening vasculitis) occurred in 37.3% of the patients receiving avacopan and in 39.0% of those receiving prednisone. CONCLUSIONS: In this trial involving patients with ANCA-associated vasculitis, avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52. All the patients received cyclophosphamide or rituximab. The safety and clinical effects of avacopan beyond 52 weeks were not addressed in the trial. (Funded by ChemoCentryx; ADVOCATE ClinicalTrials.gov number, NCT02994927.).
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Small molecule therapeutics such as avacopan and iptacopan have shown that systemic complement inhibition can safely treat systemic conditions such as paroxysmal nocturnal haemoglobinuria.
“have shown that systemic complement inhibition can safely treat systemic conditions such as paroxysmal nocturnal haemoglobinuria [233,234].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [233]
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- Authors
- Jayne, D. R. W., Merkel, P. A., Schall, T. J., & Bekker, P.
- Affiliations
- ChemoCentryx (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-02-18
- Volume
- 384
- Issue
- 7
- Pages
- 599-609
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3131777419
- Cited by
- 1,021
- References
- 37
- Citations by year
- 2026: 165 · 2025: 213 · 2024: 205 · 2023: 196 · 2022: 160 · 2021: 81 · 2017: 1
- FWCI
- 104.22
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2026-06-29)
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Apollo
- Funders
- Bristol-Myers Squibb
- AstraZeneca
- GlaxoSmithKline
- Biogen
- University of Pennsylvania
- CSL Behring
- Kiniksa Pharmaceuticals
- Insmed
- Genentech
- Janssen Biotech
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- avacopan, ANCA-associated vasculitis, C5a receptor inhibition, prednisone, remission, non-inferiority, Birmingham Vasculitis Activity Score, cyclophosphamide, rituximab, glucocorticoid tapering, adverse events, retraction, data falsification, data fabrication, data manipulation, research integrity, research misconduct
- MeSH terms
- Rituximab, Administration, Oral, Aniline Compounds, Azathioprine, Cyclophosphamide, Double-Blind Method, Drug Therapy, Combination, Female, Glucocorticoids, Humans, Immunosuppressive Agents, Male, Middle Aged, Nipecotic Acids, Prednisone, Recurrence, Remission Induction, Receptor, Anaphylatoxin C5a, Kaplan-Meier Estimate, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
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