ADVOCATE
Trial question
Is C5a receptor inhibitor avacopan noninferior to oral prednisone for the treatment of patients with ANCA-associated vasculitis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
44.0% female
56.0% male
N = 331
331 patients (144 female, 186 male)
Inclusion criteria: patients with ANCA-associated vasculitis
Key exclusion criteria: pregnant or breastfeeding, alveolar hemorrhage requiring pulmonary ventilation support at screening, any other known multi-system autoimmune disease, dialysis or plasma exchange within 12 weeks prior to screening, history of kidney transplantation, received intravenous corticosteroids > 3,000 mg methylprednisolone equivalent within 4 weeks prior to screening, taking an oral daily dose of a corticosteroid > 10 mg prednisone-equivalent for > 6 weeks continuously prior to screening
Interventions
N=166 avacopan (oral dose of 30 mg BID plus prednisone-matching placebo and cyclophosphamide or rituximab)
N=165 prednisone (an oral dose of 60 mg per day on a tapering schedule plus avacopan-matching placebo and cyclophosphamide or rituximab)
Primary outcome
Remission at week 26
72.3
70.1
72.3 %
54.2 %
36.1 %
18.1 %
0.0 %
Avacopan
Prednisone
Difference not exceeding
nonferiority margin ✓
Difference not exceeding nonferiority margin in remission at week 26 (72.3% vs. 70.1%; AD 3.4%, 95% CI -6 to 12.8)
Secondary outcomes
Significant increase in sustained remission at week 52 (65.7% vs. 54.9%; AD 12.5%, 95% CI 2.6 to 22.3)
Significant decrease in least-squares mean for Glucocorticoid Toxicity Index Cumulative Worsening Score at week 26 (39.7 vs. 56.6 ; AD -16.8 , 95% CI -25.6 to -8)
Significant decrease in least-squares mean for Glucocorticoid Toxicity Index Aggregate Improvement Score at week 26 (11.2 vs. 23.4 ; AD -12.1 , 95% CI -21.1 to -3.2)
Safety outcomes
No significant differences in any adverse events, serious adverse events, any serious infection.
Significant differences in any adverse event possibly related to corticosteroids (66.3% vs. 80.5%), life-threatening adverse event (4.8% vs. 8.5%).
Conclusion
In patients with ANCA-associated vasculitis, avacopan was noninferior to prednisone with respect to remission at week 26.
Reference
David R W Jayne, Peter A Merkel, Thomas J Schall et al. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609.
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