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.

Microscopic polyangiitis (MPA) is a necrotizing vasculitis characterized by anti-neutrophil cytoplasmic antibody against myeloperoxidase. The C5 receptor inhibitor avacopan effectively sustains remission in MPA with a reduction in prednisolone dosage. Liver damage is a safety concern for this drug. However, when it occurs and how to treat it remains unknown. A 75-year-old man developed MPA 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 nine weeks, liver dysfunction and sparse skin eruptions developed. Cessation of avacopan and initiation of ursodeoxycholic acid (UDCA) improved liver function without discontinuation of prednisolone and other concomitant drugs. After three weeks, avacopan was rechallenged with a small dose which was gradual increased; UDCA was continued. Full-dose avacopan did not induce recurrence of liver injury. Therefore, gradually increasing the dose of avacopan with concomitant UDCA use may help avoid possible avacopan-induced liver injury.