Is avacopan better than prednisone for respiratory ANCA-associated vasculitis outcomes?

An exploratory subgroup analysis of the phase 3 ADVOCATE trial showed that avacopan was only somewhat better than prednisone at reducing respiratory, as well as ear, nose, and throat (ENT), involvement in patients with ANCA-associated vasculitis. However, reduced glucocorticoid use in the avacopan group was a clear clinical benefit.

Prof. Ulrich Specks (Mayo Clinic, MN, USA) presented the respiratory and ENT outcomes of the phase 3 ADVOCATE trial (NCT02994927) [1]. ADVOCATE was a phase 3, randomised, double-blind, double-dummy, controlled clinical study comparing the selective neutrophil C5aR inhibitor avacopan (plus prednisone-matching placebo) with prednisone (plus avacopan-matching placebo) in addition to either cyclophosphamide (followed by azathioprine) or rituximab. The trial results demonstrated the efficacy of avacopan in helping patients with ANCA-associated vasculitis achieve disease remission at 6 months and sustained remission at 12 months, which was published last year in the New England Journal of Medicine [2]. When the 330 patients included in this subgroup analysis were stratified by the phenotype of their disease, pulmonary involvement was more common in patients with granulomatosis with polyangiitis (54%; 98/181) than with microscopic polyangiitis (30%; 45/149).

The primary endpoint was the percentage of patients achieving disease remission at week 26, and sustained remission at week 52. Disease remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and no glucocorticoids within 4 weeks prior to week 26. Sustained remission was remission at week 26 and week 52 and no glucocorticoid use 4 weeks prior to week 52. Lung and ENT involvement was defined as BVAS-detected active vasculitis in the upper and lower respiratory tract.

Results indicated an overall glucocorticoid use reduction by a median of 86% in the avacopan group, with data pointing to a 26-week non-inferiority significance, improving to a 52-week superiority significant remission compared to the prednisone group. Although rates of both lung and ENT involvement were numerically lower in the avacopan group than in the prednisone group, the differences were not statistically significant. At baseline, 43% of patients (143/330) had evident lung involvement. At weeks 26 and 52, the avacopan group lung involvement was present in 0.6% (1/166) and 0% (0/166) of patients, respectively. At weeks 26 and 52 the placebo, in comparison, had 2.4% (4/164) and 1.8 % (3/164) of patients, respectively. Similarly, ENT involvement at baseline was present in 44% of patients (144/330). In the avacopan group, ENT involvement was present in 1.2% (2/166) of patients at both weeks 26 and 52. In the prednisone group, ENT involvement was present in 3.7% (6/164) and 3.0% (5/164) of patients, at weeks 26 and 52, respectively.

“The overall results of the ADVOCATE trial are very exciting as they indicate that patients with ANCA-associated vasculitis receiving avacopan can achieve sustained remission with minimal glucocorticoid exposure,” Prof. Specks said. “While the results presented here for the subset of patients with lung and ENT involvement are most promising, the specific effect of avacopan on individual disease manifestations requires further study.”

1. Specks U, et al. Insights from the ADVOCATE study: Respiratory tract involvement in patients with ANCA-associated vasculitis in a randomised, double-blind, placebo-controlled phase 3 trial of avacopan. Session C93, ATS International Conference 2022, San Francisco, CA, USA, 13–18 May.
2. Jayne DRW, et al. N Engl J Med. 2021 Feb 18;384(7):599–609.

 

 

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Posted on 19 May, 2022