Gradual increase of avacopan dose with concomitant ursodeoxycholic acid use may help avoid the risk of C5a receptor inhibitor-induced liver injury in antineutrophil cytoplasmic antibody-associated vasculitis

Mod Rheumatol Case Rep. 2023 Jun 19;7(2):444-447. doi: 10.1093/mrcr/rxad019.

Abstract

Microscopic polyangiitis is a necrotising vasculitis characterised by anti-neutrophil cytoplasmic antibodies against myeloperoxidase. The complement component 5a receptor inhibitor avacopan effectively sustains remission in microscopic polyangiitis with a reduction in prednisolone dosage. Liver damage is a safety concern for this drug. However, when it occurs and how to treat it remain unknown. A 75-year-old man developed microscopic polyangiitis and presented with hearing impairment and proteinuria. Methylprednisolone pulse therapy followed by 30 mg/day prednisolone and two doses of weekly rituximab were administered. Avacopan was initiated to taper prednisolone for sustained remission. After 9 weeks, liver dysfunction and sparse skin eruptions developed. The cessation of avacopan and the initiation of ursodeoxycholic acid improved liver function without discontinuation of prednisolone and other concomitant drugs. After 3 weeks, avacopan was rechallenged with a small dose that was gradually increased; ursodeoxycholic acid was continued. Full-dose avacopan did not induce recurrence of liver injury. Therefore, gradually increasing the dose of avacopan with concomitant ursodeoxycholic acid use may help avoid possible avacopan-induced liver injury.

Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis; avacopan; liver injury.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis*
  • Antibodies, Antineutrophil Cytoplasmic
  • Chemical and Drug Induced Liver Injury, Chronic* / drug therapy
  • Humans
  • Immunologic Factors / therapeutic use
  • Male
  • Microscopic Polyangiitis* / drug therapy
  • Prednisolone
  • Receptor, Anaphylatoxin C5a
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • avacopan
  • Receptor, Anaphylatoxin C5a
  • Ursodeoxycholic Acid
  • Prednisolone
  • Immunologic Factors