Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage

Aglaia Chalkia; Oliver Flossmann; Rachel Jones; Jagdish Ramachandran Nair; Thomas Simpson; Rona Smith; Lisa Willcocks; David Jayne

doi:10.1093/ndt/gfae020

Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage

Nephrol Dial Transplant. 2024 Jan 24:gfae020. doi: 10.1093/ndt/gfae020. Online ahead of print.

Authors

Aglaia Chalkia¹, Oliver Flossmann², Rachel Jones^{1

3}, Jagdish Ramachandran Nair⁴, Thomas Simpson⁵, Rona Smith^{1

3}, Lisa Willcocks³, David Jayne^{1

3}

Affiliations

¹ Department of Medicine, University of Cambridge, UK.
² Department of Nephrology, Royal Berkshire Hospital, Reading, UK.
³ Vasculitis & lupus Clinic, Addenbrooke's Hospital Cambridge, UK.
⁴ Department of Rheumatology, Liverpool University Hospital, UK.
⁵ Department of Respiratory Medicine, Lewisham Hospital, UK.

PMID: 38268434
DOI: 10.1093/ndt/gfae020

Abstract

Background and hypothesis: Pulmonary haemorrhage with hypoxia caused by ANCA-associated vasculitis (AAV) has a high early mortality. Avacopan, an oral C5a receptor antagonist, is an approved treatment for AAV, but patients with pulmonary haemorrhage requiring invasive pulmonary ventilation support were excluded from the ADVOCATE trial.

Methods: A retrospective, observational, multicentre case series of AAV patients with hypoxic pulmonary haemorrhage, requiring oxygen support or mechanical ventilation, who received avacopan.

Results: Eight patients (62.5% female), median age 64 years (range 17-80), seven with kidney involvement, median glomerular filtration rate (GFR) 11 (range 5-99) ml/min per 1.73m2, were followed for a median of 6 months from presentation. Seven were newly diagnosed (87.5%), five were MPO-ANCA and three PR3-ANCA positive. All had hypoxia, four requiring mechanical ventilation (three invasive and one non-invasive). Intensive care unit (ICU) stay for the four patients lasted a median of 9 days (range 6-60). Four received rituximab and cyclophosphamide combination, three rituximab and one cyclophosphamide. Four underwent plasma exchange and one received two months of daily extracorporeal membrane oxygenation (ECMO) therapy. Following the initiation of avacopan after a median of 10 days (range 2-40), pulmonary haemorrhage resolved in all patients, even two who had one month of refractory pulmonary haemorrhage prior to avacopan. Additionally, after one month, the median prednisolone dose was 5 mg/day (range 0-50), with three patients successfully discontinuing steroid use. Two patients suffered serious infections, two discontinued avacopan, one permanently due to a rash and one temporarily after three months due to neutropenia. All patients survived and no re-hospitalization occurred.

Conclusion: We report the use of avacopan as a component of the treatment for pulmonary haemorrhage with hypoxia in AAV. Despite the life-threatening presentations all patients recovered, but attribution of the positive outcomes to avacopan is limited by the concomitant therapies and retrospective observational design.

Keywords: ANCA; avacopan; hypoxia; pulmonary haemorrhage; vasculitis.