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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, . ,

. 2017 ; 28 (9) : 2756-2767. [pub] 20170411

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, multicentrická studie, randomizované kontrolované studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc18016668
E-zdroje Online Plný text

NLK Free Medical Journals od 1990 do Před 1 rokem
PubMed Central od 2008 do Před 1 rokem
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Open Access Digital Library od 1990-07-01

Odkazy

PubMed 28400446
DOI 10.1681/asn.2016111179
Knihovny.cz E-zdroje

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.

Citace poskytuje Crossref.org

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