Abstract / Summary
Objective: Complement activation, particularly through the C5a-C5a receptor axis, plays a pivotal role in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and may represent an important therapeutic target. Avacopan, an oral C5a receptor antagonist, was the first therapy targeting this pathway to enter in clinical practice. Prospective real-world data on its long-term effectiveness, safety, and impact on quality of life (QoL) remain limited. In the context of an evolving therapeutic and regulatory landscape, such data provide valuable evidence on the clinical effects of C5a receptor inhibition and may inform the development and evaluation of future complement-targeted therapies. The objective of this study was to evaluate the real-world effectiveness, safety, kidney outcomes, and patient-reported outcomes of avacopan in an Italian cohort of patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).
Methods: This prospective, multicenter, observational study included patients with newly diagnosed or relapsing GPA or MPA who were started on avacopan therapy across 18 Italian centers. Avacopan was administered in combination with standard immunosuppressive therapy, with or without glucocorticoids (GCs). Clinical remission (Birmingham Vasculitis Activity Score = 0), GC-free remission, kidney parameters, laboratory outcomes, adverse events, and patient-reported outcomes assessed by the AAV Patient-Reported Outcome questionnaire were evaluated up to 52 weeks and beyond. Estimated glomerular filtration rate (eGFR) was calculated using the European Kidney Function Consortium equation.
Results: Forty-six patients were included (63% women; mean age of 59 years); 61% had relapsing disease, and 70% had kidney involvement at baseline. Clinical remission was achieved by 78%, 88%, and 97% of patients at weeks 12, 26, and 52, respectively. GC-free remission occurred in 20% at week 12 and 55% at week 52. Mean GC dose decreased from 23 mg/day at baseline to 5 mg/day by week 12 (P < 0.001). Kidney function improved over time, with median eGFR increasing from 30.5 mL/min/1.73 m2 at baseline to 53.5 mL/min/1.73 m2 at week 52 (P = 0.002). Significant improvements in QoL were observed as early as week 12 and were sustained until week 52, particularly in the physical function domain. Adverse events were mild to moderate; infections were the most frequent events (40%). Disease relapses were uncommon and occurred exclusively in patients treated for relapsing disease.
Conclusion: In this real-world Italian cohort, patients treated with avacopan achieved high remission rates, substantial GC reduction, improvement in kidney function, and sustained QoL benefits. These findings provide prospective real-world evidence on the clinical outcomes associated with C5a receptor inhibition in routine clinical practice while acknowledging the observational design of the study.