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Abstract: SA-PO0870

Avacopan for Severe ANCA-Associated Vasculitis: Uncharted Waters

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Olowoyo, Olamide, Geisinger Medical Center, Danville, Pennsylvania, United States
  • Bobak, Angela L, Geisinger Medical Center, Danville, Pennsylvania, United States
  • Riaz, Ramsha, Geisinger Medical Center, Danville, Pennsylvania, United States
  • Koons, Kirsten, Geisinger Medical Center, Danville, Pennsylvania, United States
  • George, Jason Christopher, Geisinger Medical Center, Danville, Pennsylvania, United States
Introduction

ANCA-associated vasculitis (AAV) often presents with severe/potentially life-threatening organ dysfunction. Glucocorticoids are used as part of induction therapy; prolonged courses are frought with adverse effects/infectious complications. The C5a receptor inhibitor avacopan is effective in achieving/sustaining remission of severe, active AAV and can allow for rapid steroid tapering. Data in those with severe kidney/lung involvement are currently limited. We present a case series of AAV patients with severe kidney and/or lung involvement treated with avacopan with good response/tolerance.

Case Description

We describe 5 patients with severe, active AAV and either acute respiratory failure/alveolar hemorrhage or severe AKI. Patients ranged from age 19-73. Three with respiratory failure required intubation; two required ECMO support for severe ARDS. Those with severe AKI had GFR <15 mL/min or required kidney replacement therapy (KRT). All patients underwent plasmapheresis. Induction therapy included pulse steroids and rituximab. In addition, all patients were treated with avacopan with overall good tolerance/response. All achieved partial or complete vasculitis remission within 1 year. Two patients who required KRT recovered kidney function. Those with respiratory failure had significant improvement in oxygenation.

Discussion

Use of anti-complement therapy has become a topic of interest in treatment of severe, active AAV. In a large randomized, controlled trial of patients with severe, active AAV, avacopan was effective in achieving/sustaining remission at week 26 and 52, respectively. Patients with GFR <15 mL/min (or need for KRT within 12 weeks) and severe diffuse alveolar hemorrhage (DAH) were excluded, and there remains a paucity of outcome data for use of avacopan in such patients. All patients in our series presented with either severe AKI (GFR <15 or requiring KRT) or DAH. In addition, two patients with severe ARDS required ECMO, highlighting their aggressive state of disease. Despite the severity of illness, our patients were able to initiate avacopan in a closely-monitored inpatient setting. Other than transient liver enzyme abnormalities, avacopan was well-tolerated. AAV remains a life-threatening disease. Its increasing global prevalance and the evolving role of anti-complement therapy shed light on avacopan's potential role in more severe cases.

Digital Object Identifier (DOI)