Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis
(2017) In Journal of the American Society of Nephrology 28(9). p.2756-2767- Abstract
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 glucocorticoidswithout 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... (More)
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 glucocorticoidswithout 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, 24.3% 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, 211.0% 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.
(Less)
- author
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Society of Nephrology
- volume
- 28
- issue
- 9
- pages
- 2756 - 2767
- publisher
- American Society of Nephrology
- external identifiers
-
- scopus:85028646927
- pmid:28400446
- ISSN
- 1046-6673
- DOI
- 10.1681/ASN.2016111179
- language
- English
- LU publication?
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- id
- b784ad8c-c2a4-4dc4-9c24-1887e7b59baa
- date added to LUP
- 2020-06-23 16:35:52
- date last changed
- 2024-09-20 00:26:45
@article{b784ad8c-c2a4-4dc4-9c24-1887e7b59baa,
abstract = {{<p>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 glucocorticoidswithout 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, 24.3% 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, 211.0% 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.</p>}},
author = {{Jayne, David R.W. and Bruchfeld, Annette N. and Harper, Lorraine and Schaier, Matthias and Venning, Michael C. and Hamilton, Patrick and Burst, Volker and Grundmann, Franziska and Jadoul, Michel and Szombati, István and Tesar, Vladimír and Segelmark, Mårten and Potarca, Antonia and Schall, Thomas J. and Bekker, Pirow}},
issn = {{1046-6673}},
language = {{eng}},
number = {{9}},
pages = {{2756--2767}},
publisher = {{American Society of Nephrology}},
series = {{Journal of the American Society of Nephrology}},
title = {{Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis}},
url = {{http://dx.doi.org/10.1681/ASN.2016111179}},
doi = {{10.1681/ASN.2016111179}},
volume = {{28}},
year = {{2017}},
}