Treatment with avacopan, in combination with standard therapy such as glucocorticoids, was approved recently by the US Food and Drug Administration as an adjunctive treatment for adults with severe, active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Findings from the current case study, which were published in the Journal of Nephrology, describe a 58-year-old previously healthy Asian female with severe AAV and acute renal failure. Despite being refractory to rituximab and glucocorticoid therapy, the patient appears to have responded to adjunctive treatment with avacopan.

Individuals with AAV often present with end-organ damage, which can be associated with significant morbidity and mortality. In these patients, early diagnosis of disease and the use of innovative therapeutic approaches are essential to optimal care.

The patient was originally referred to the rheumatology department for joint pain. Her initial treatment was 20 mg of prednisolone daily with a presumed diagnosis of polymyalgia rheumatica. She went on to develop fatigue, headaches, gastrointestinal symptoms, and ear fullness, along with unresolved joint pain.

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Several weeks later, she presented to the emergency department, and was ultimately hospitalized with acute kidney injury and lower left extremity deep vein thrombosis. ANCA titers were detected, and the patient was diagnosed with microscopic polyangiitis—a common presentation of AAV—and rapidly progressive glomerulopathy.

Her initial treatment involved pulse methylprednisolone and intravenous rituximab. She was eventually discharged home on 50 mg of methylprednisolone per day. Attempts at a methylprednisolone taper resulted in recurrent acute kidney injury and joint pain, and the patient ultimately developed steroid-associated adverse events, including hypertension, type 2 diabetes, and fluid overload.

The patient presented back to the hospital with worsening acute kidney injury. She was initially treated with pulse methylprednisolone and intravenous rituximab once again. She was discharged home again on 50 mg of methylprednisolone daily. When her renal disease continued to worsen after 2.5 weeks, avacopan therapy was initiated. Within 2 days of avacopan treatment, her serum creatinine counts began to normalize.

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She has now received avacopan therapy for 10 months and is considered to be in sustained disease remission. After tapering, methylprednisolone eventually was discontinued. Continued renal improvement after treatment with avacopan has been reported. Her type 2 diabetes and hypertension have resolved. No avacopan-associated adverse events have been reported.

In patients with AAV, the alternative complement pathway has been shown to play a key role. The complement anaphylatoxin C5a is one of the most potent proinflammatory peptides to interact with C5aR and prime neutrophils, thus augmenting AAV-induced neutrophil activation.

“As the optimal treatment for refractory ANCA-associated vasculitis has not yet been thoroughly defined, further studies are needed to determine the potential role of avacopan in these cases,” the researchers concluded.


Alvarez L, Kambham N, Su R. Renal improvement and remission in a patient with refractory ANCA-associated vasculitis treated with avacopan. J Nephrol. Published online April 10, 2023. doi:10.1007/s40620-023-01614-y