Avacopan Superior to Standard Therapy in Renal Function in ANCA-Associated Vasculitis

Photomicrograph of the kidney
Photomicrograph of the kidney
Study authors evaluated the effect of complement C5a receptor inhibitor avacopan on renal function in ANCA-associated vasculitis.

The following article is a part of conference coverage from the American College of Rheumatology Convergence 2020, being held virtually from November 5 to 9, 2020. The team at Rheumatology Advisor will be reporting on the latest news and research conducted by leading experts in rheumatology. Check back for more from the ACR Convergence 2020.

Avacopan can improve sustained remission rates and may be superior to standard therapy in renal function in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, according to study results presented at the American College of Rheumatology (ACR) Convergence 2020, held virtually from November 5 to 9, 2020.

Previous research has indicated that avacopan, an orally administered complement C5a receptor inhibitor, is superior to prednisone in patients with ANCA-associated vasculitis. The objective of the current analysis was to determine changes in renal function during treatment with avacopan.

The study sample included 330 participants who were randomly assigned to receive avacopan 30 mg twice daily (n=166) or prednisone therapy (n=164).

The primary efficacy end points were the percentage of patients achieving disease remission at 26 weeks and sustained disease remission at week 52, determined by the Birmingham Vasculitis Activity Score (BVAS).

At week 26, remission rates were 72.3% for the avacopan group compared with 70.1% for the prednisone group (P <.0001 noninferiority). At week 52, avacopan was statistically superior to prednisone with remission rates of 65.7% vs 54.9%, respectively (P =.0066).

Furthermore, time to relapse after remission (BVAS=0) was longer for the avacopan group compared with the prednisone group (P =.0091) and the hazard ratio for time to relapse was 0.46 (95% CI, 0.25-0.84). Efficacy was observed in various subgroup analyses.

In patients with renal disease at baseline, improvement in renal function, as determined by estimated glomerular filtration rate (eGFR), was greater with avacopan compared to prednisone therapy (7.3 mL/min/1.73 m2 vs 4.1 mL/min/1.73 m2, respectively; P =.029). Among patients with baseline eGFR less than 30 mL/min/1.73 m2, the difference between prednisone and avacopan was the greatest.

Reduction in albuminuria was significantly more rapid with avacopan than placebo. At 4 weeks, avacopan was associated with a 40% reduction in albuminuria, while there was no change with prednisone. However, at week 52, no difference was reported between groups.

Serious adverse events were reported in 166 patients who received prednisone compared with 116 who received avacopan, indicating avacopan had a better safety profile than standard prednisone therapy. Serious infections were observed in 31 patients who received prednisone compared with 25 who received avacopan. Rates of white blood cell count decrease were 4.9% vs 2.5%, respectively and liver function test increases in 3.7% of patients who received avacopan compared with 5.4% of those who received prednisone.

“These findings suggest the potential for better long-term outcomes with avacopan for patients with renal disease than current standard of care treatment and provide intriguing insights into subclinical renal disease activity in ANCA-associated vasculitis,” the study authors concluded.

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Merkel P, Bekker P, Yue H, Kelleher C, Schall T, Jayne D. The effect on renal function of the complement C5a receptor inhibitor avacopan in ANCA-associated vasculitis. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract 0432.