Is There a Place for Complement Inhibition with Monoclonal Anti-C5a Antibody Vilobelimab in the Treatment of Patients with ANCA-associated Vasculitis?

Rheumatology(2022)

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Abstract
Recent studies have implicated the complement system in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), prompting the development of novel therapeutic agents to target the complement system accordingly. The pivotal role of complement component C5a, in particular, has been the subject of a number of phase II and phase III clinical trials. Indeed, the US Food and Drug Administration has already approved avacopan, an oral C5a receptor inhibitor, as an adjunct for the treatment of active severe AAV, based on its favourable safety profile and non-inferiority to glucocorticoids (GCs) (at Week 26). The novel monoclonal anti-C5a antibody vilobelimab has also been studied in a phase II trial in patients with AAV (IXchange; ClinicalTrials.gov Identifier: NCT03895801). The results appear promising; in addition to decreased GC toxicity index, a smaller number of treatment-emergent adverse events have been observed in vilobelimab-treated patients. However, the study was not powered statistically to compare the efficacy of vilobelimab to standard GC treatment. This editorial summarizes the study findings and outlines potential future directions.
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Key words
complement inhibition,vasculitis,treatment,anca-associated
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