Treatment With Avacopan in ANCA-Associated Vasculitis With Kidney Involvement

Abstract

Introduction: Kidney disease impacts long-term outcomes of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). This post hoc analysis evaluated the effect of avacopan in a subgroup of patients with GPA or MPA and kidney involvement at baseline from the ADVOCATE trial.

Methods: The analysis included a study population of 268 patients (of 330 patients, 81.2%). Key efficacy outcomes were remission at week 26, sustained remission at week 52, and relapse after remission through week 52. Changes in estimated glomerular filtration rate (eGFR) were analyzed overall and stratified by baseline eGFR categories (≥ 90, 60-89, 45-59, 30-44, and 15-29 ml/min per 1.73 m²). Additional outcomes were changes in albuminuria and hematuria, glucocorticoid (GC) use, glucocorticoid toxicity index (GTI), and safety.

Results: Remission at week 26 and sustained remission at week 52, respectively, were respectively achieved by 99 of 134 (73.9%) and 91 of 134 (67.9%) patients in the avacopan group and 95 of 134 (70.9%) and 76 of 134 (56.7%) in the prednisone taper group. Relapse rate after remission was lower in the avacopan than in the prednisone taper group (9.4% vs. 20.9%; hazard ratio [95% confidence interval, CI]: 0.43 [0.22-0.85]). Recovery of kidney function, speed of reduction in albuminuria and hematuria, and changes in GTI favored the avacopan group. No new safety issues were reported for this subset of patients.

Conclusion: In patients with GPA or MPA with kidney involvement, treatment with an avacopan regimen compared with a prednisone taper regimen achieved similar rates of remission, improved recovery of kidney function, led to faster reduction in albuminuria and hematuria, and lowered GC-related toxicity, with an acceptable safety profile.

Keywords: ANCA; complement; granulomatosis with polyangiitis (GPA); hematuria; microscopic polyangiitis (MPA); proteinuria.

Graphical abstract

Figure 1

Percentage of patients with active kidney manifestations over time for (a) prednisone taper and (b) avacopan. hpf, high powered field; RBC, red blood cell.

Figure 2

Change in eGFR category between baseline and week 52 in patients with eGFR ≥ 15 ml/min per 1.73 m² at baseline. N includes patients with baseline eGFR ≥ 15 ml/min per 1.73 m² and an eGFR assessment at week 52. Red: patients who had a worse eGFR category at week 52 compared with eGFR category at baseline. Yellow: patients who had the same eGFR category at week 52 as baseline. Green: patients who had an improved eGFR category at week 52 compared with eGFR category at baseline. eGFR, estimated glomerular filtration rate.

Figure 3

Change in UACR in patients with kidney involvement. (a) Change in UACR from baseline in patients with kidney involvement and baseline UACR > 300 mg/g. (b) Change in UACR from baseline in patients with baseline UACR > 300 mg/g and baseline adjudicated BVAS item rise in serum creatinine > 30% or fall in creatinine clearance > 25%. (c) Percentage of patients achieving either a UACR < 300 mg/g or a > 30% reduction in albuminuria. ^∗Imprecise estimations because of the limited patient number. LS mean and SEM calculated from mixed effects models for repeated measures with treatment group, visit, and treatment-by-visit interaction as factors; and baseline as a covariate. Logarithmic transformations were applied to the data before fitting the model. Percent changes from baseline are based on ratios of geometric means of visit over baseline. CI, confidence interval; BVAS, Birmingham Vasculitis Activity Score; eGFR, estimated glomerular filtration rate; LS, least squares; UACR, urinary albumin-to-creatinine ratio.

Figure 4

Changes in hematuria in patients with kidney involvement. (a) Percentage of patients with kidney involvement and hematuria at baseline by hematuria categories of none, 1 to < 10, 10 to 29, 30 to 49, 50 to 75, > 75 RBCs/hpf. (b) Percentage of patients with baseline hematuria ≥ 10 RBCs/hpf who achieved urinary RBC count < 10/hpf or < 3/hpf at any time during the 52 weeks. Missing central laboratory urinalysis was imputed as no achievement. hpf, high powered field; RBC, red blood cell.