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.

• MeSH
• ANCA-asociované vaskulitidy farmakoterapie   MeSH
• aniliny škodlivé účinky   terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• glukokortikoidy aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• kombinovaná farmakoterapie škodlivé účinky   MeSH
• kyseliny nipekotinové škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prednison aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• receptor pro anafylatoxin C5a antagonisté a inhibitory   MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• Klíčová slova
• studie CLEAR, avacopan,
• MeSH
• ANCA-asociované vaskulitidy * farmakoterapie   MeSH
• aniliny škodlivé účinky   terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• glukokortikoidy škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kyseliny nipekotinové škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• prednison škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor pro anafylatoxin C5a antagonisté a inhibitory   MeSH
• rituximab terapeutické užití   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission. METHODS: We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point. RESULTS: Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03). CONCLUSIONS: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.

• MeSH
• azathioprin škodlivé účinky   terapeutické užití   MeSH
• cyklofosfamid škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• financování organizované MeSH
• glukokortikoidy terapeutické užití   MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• indukce remise MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutropenie chemicky indukované   MeSH
• prednisolon terapeutické užití   MeSH
• protilátky proti cytoplazmě neutrofilů krev   MeSH
• randomizované kontrolované studie jako téma MeSH
• recidiva MeSH
• senioři MeSH
• vaskulitida farmakoterapie   imunologie   mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH