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Complement inhibition in ANCA vasculitis.

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Peer-reviewed

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Article

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Abstract

A role for the alternative complement pathway has emerged in the understanding of ANCA vasculitis pathogenesis. Current therapies of ANCA vasculitis are limited by partial efficacy and toxicity and many patients pursue a relapsing course. Improved therapies are needed. Inhibition of the alternative complement pathway component C5a is attractive due to its role in neutrophil activation and migration, and engagement of other inflammatory and thrombotic mechanisms. Two inhibitors of C5a are in clinical development for ANCA vasculitis: avacopan, an oral C5a receptor inhibitor has demonstrated efficacy, safety and steroid sparing in two Phase II trials; and IFX-1, a monoclonal antibody to C5a which is entering Phase II development. Complement inhibition has the potential to contribute to remission induction protocols achieving a higher quality of remission as well as replacing steroids. Confirmation of safety, especially infective risk, and the potential to replace steroids depends on further studies and a role in relapse prevention needs to be explored.

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Keywords

ANCA, C5a, Clinical trial, Complement, Therapy, Vasculitis, Aniline Compounds, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Monoclonal, Clinical Trials, Phase II as Topic, Complement C5a, Complement Inactivating Agents, Complement Pathway, Alternative, Humans, Neutrophil Activation, Nipecotic Acids

Journal Title

Nephrol Ther

Conference Name

Journal ISSN

1769-7255
1872-9177

Volume Title

15

Publisher

John Libbey Eurotext