Avacopan Achieves Sustained Remission in Real World Severe ANCA Vasculitis Data, With Naomi Patel, MD

Real-world use of avacopan in ANCA-associated vasculitis (AAV) mirrors and in some respects extends the promise of the pivotal ADVOCATE trial — with 61% of patients achieving sustained remission at 12 months, nearly all off glucocorticoids within 3 months, and a reassuring safety profile in a heterogeneous clinical population that reflects the complexity of everyday practice.

The data come from an ongoing retrospective cohort study conducted within a large United States (US) healthcare system, identifying patients prescribed avacopan for severe active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) between December 2021 and April 2024. Of 119 patients prescribed avacopan, 103 (87%) initiated therapy — with the most common barrier to initiation being insurance denial (n = 5) or high copay (n = 3). Among those initiating, 95 had complete 12-month follow-up data available for the primary analysis.

The cohort had a mean age of 59.4 years; most were female (n = 83; 70%), newly diagnosed (n = 79; 66%), and split roughly evenly between GPA (n = 60; 50%) and MPA. The majority were MPO-ANCA positive (n = 66; 55%), with a median baseline Birmingham Vasculitis Activity Score version 3 (BVAS v3) of 12 (IQR 8–17), indicating predominantly severe disease. Most received concomitant rituximab (n = 65; 55%), cyclophosphamide (n = 6; 5%), or both (n = 39; 33%). To discuss the findings and their implications for how avacopan is being deployed outside of trial conditions, we spoke with Naomi Patel, MD, the study's lead investigator.

Among the 95 patients with available 12-month follow-up, sustained remission — defined as BVAS v3 = 0 at both months 6 and 12, no glucocorticoid use for GPA/MPA within one month before each timepoint, and no relapse between months 6 and 12 — was achieved in 58 patients (61%). At month 12, 90 patients (95%) had a BVAS v3 of 0 and 83 (87%) were glucocorticoid-free. Relapse between months 6 and 12 was uncommon, occurring in just three patients: 1 major relapse and 2 minor relapses. The glucocorticoid-sparing effect was particularly notable: among 84 patients on glucocorticoids at baseline, 72 discontinued after a median of 84 days (IQR, 56–175), with a median cumulative prednisone-equivalent exposure over the full 12-month period of just 1,050 mg (IQR, 280–2,030 mg). Of the 57 patients who discontinued avacopan before 12 months, the majority did so because the provider had completed the planned treatment course (n = 33, 58%), while 14 (25%) discontinued due to adverse events, most commonly aminotransferase elevation (n = 5; 5% of the full cohort).

On glucocorticoid toxicity, 56% of patients showed no net worsening of metabolic domains as assessed by the GTI-MD aggregate improvement score (AIS ≤ 0), with blood pressure the most commonly affected domain showing net worsening (41%), followed by BMI (21%), lipid metabolism (18%), and glucose tolerance (5%). Sustained remission rates were consistent across patients with kidney, lung, or ENT involvement at baseline.

“In this real world cohort that the glucocorticoid sparing ability of avacopan was pretty impressive. So previously, glucocorticoid regimens lasted 6 months, even longer, 12 months or longer in AAV, and we found that the median time to discontinuation of glucocorticoids in this cohort was 84 days, meaning that over half of individuals were off of steroids by 3 months after the initiation of avacopan, which is really impressive compared to prior regimens that we used to use,” Patel said.

Patel’s reported disclosures include Amgen.

Reference

Patel N, King A, Negron M, et al. One Year Real-World Effectiveness with Avacopan in Granulomatosis with Polyangiitis and Microscopic Polyangiitis in a Large Healthcare System. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #1606