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Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis
DRW. Jayne, AN. Bruchfeld, L. Harper, M. Schaier, MC. Venning, P. Hamilton, V. Burst, F. Grundmann, M. Jadoul, I. Szombati, V. Tesař, M. Segelmark, A. Potarca, TJ. Schall, P. Bekker, . ,
Language English Country United States
Document type Journal Article, Multicenter Study, Randomized Controlled Trial
NLK
Free Medical Journals
from 1990 to 1 year ago
PubMed Central
from 2008 to 1 year ago
Europe PubMed Central
from 2008 to 1 year ago
Open Access Digital Library
from 1990-07-01
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis drug therapy MeSH
- Aniline Compounds adverse effects therapeutic use MeSH
- Cyclophosphamide therapeutic use MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Glucocorticoids administration & dosage adverse effects therapeutic use MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Drug Therapy, Combination adverse effects MeSH
- Nipecotic Acids adverse effects therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Prednisone administration & dosage adverse effects therapeutic use MeSH
- Receptor, Anaphylatoxin C5a antagonists & inhibitors MeSH
- Rituximab therapeutic use MeSH
- Aged MeSH
- Severity of Illness Index MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.
Budai Irgalmasrendi Korhaz Budapest Hungary
ChemoCentryx Inc Mountain View California
Department of Medicine Addenbrooke's Hospital Cambridge United Kingdom
Department of Nephrology Charles University Prague Czech Republic
Department of Nephrology Linköping University Linköping Sweden
Department of Renal Medicine Karolinska University Hospital Huddinge Stockholm Sweden
Department of Renal Medicine Manchester Royal Infirmary Manchester United Kingdom
Renal Centre University of Heidelberg Heidelberg Germany
Service de Nephrologie Cliniques Universitaires Saint Luc Brussels Belgium
References provided by Crossref.org
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