Expanding the role of avacopan beyond renal involvement: Clinical insights from two cases

Granulomatosis with polyangiitis is a necrotising small vessel vasculitis characterised by granulomatous inflammation that can involve the eyes, ear-nose-throat region, and lungs, often refractory to standard immunosuppressive therapies such as glucocorticoids, rituximab, and cyclophosphamide. The complex immunopathogenesis of granulomatous lesions, involving neutrophil swarming, macrophage activation, T-cell responses, and complement activation through the C5a receptor, contributes to treatment challenges. Avacopan, an oral C5a receptor antagonist, has demonstrated efficacy in antineutrophil cytoplasmic antibody-associated vasculitis, particularly in kidney involvement, with evidence of glucocorticoid-sparing benefits from the ADVOCATE trial. However, data on its role in granulomatous manifestations remain limited. We report two cases of severe, refractory granulomatosis with polyangiitis with ocular, ear-nose-throat, and pulmonary granulomatous disease unresponsive to standard therapies but achieving complete clinical and immunological remission with avacopan. Both patients successfully discontinued glucocorticoids and showed marked clinical improvement and radiological resolution of lesions. These cases, supported by recent trial sub-analyses, suggest that avacopan may be an effective therapeutic option for granulomatous granulomatosis with polyangiitis manifestations, enabling glucocorticoid reduction and improved disease control.