Spanish Journal of Medicine - Volume 2 - Issue 4 - Original Articles - Avacopan and Complement Blockade in ANCA-Associated Vasculitis

Sep 25, 2026

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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is driven by ANCA, especially PR3- and MPO-directed antibodies, which stimulate neutrophils and activate the alternative complement pathway. This leads to C5a generation, a key anaphylatoxin that amplifies inflammation by recruiting and activating additional neutrophils and increasing vascular permeability. Remission induction currently relies on glucocorticoids combined with rituximab or cyclophosphamide, with limited options. Avacopan offers targeted inhibition of C5aR1, aiming to reduce glucocorticoid exposure without compromising efficacy.

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Original Articles

Complement blockade in the management of antineutrophil cytoplasmic antibody-associated vasculitis

Diagnosis delay, phenotypic variety, and therapeutic outcome of Erdheim-Chester disease

Review Article

Author-level metrics: h-index and beyond

Spanish Journal of Medicine [www.SpanishJMed.com](www.SpanishJMed.com) Volume 2, Issue 4, October-December 2022 eISSN: 2696-5631 ORIGINAL ARTICLES | Complement blockade in the management of antineutrophil cytoplasmic antibodyassociated vasculitis
José Salvador García-Morillo, Ricardo Blanco-Alonso, and Enrique Morales-Ruiz
Diagnosis delay, phenotypic variety, and therapeutic outcome of Erdheim-Chester disease
Andrea Rodríguez Trigueros, José Ramón Lopez-Morales, José Carlos Alarcón García,
Santiago Rodríguez Suárez, Pilar Sancho, and José Salvador García-Morillo
REVIEW ARTICLE | | --- | | Author-level metrics: h-index and beyond
José M. Porcel and Leyre Liesa
SPANISH JOURNAL OF MEDICINE REVIEWERS 2022 | PERMANYER [www.permanyer.com](www.permanyer.com) Spanish Journal of Medicine Original artiCle Complement blockade in the management of antineutrophil cytoplasmic antibody-associated vasculitis José Salvador García-Morillo1 *, Ricardo Blanco-Alonso2, and Enrique Morales-Ruiz3 1Autoimmune and Minority Diseases Unit. Internal Medicine Department. Hospital Universitario Virgen del Rocío, Sevilla. Systemic Autoimmune Diseases Working Group (GEAS-SEMI), Spain; 2Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain; 3Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain abstract Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are characterized by the presence of ANCA, particularly those directed against proteinase 3 (PR3) or myeloperoxidase (MPO). At present, the most accepted pathogenic pathway is based on the pathogenic nature of ANCA, which stimulate neutrophils with the consequent activation of the alternative complement pathway, leading to the production of C5a, an anaphylatoxin which plays a key role in amplifying the inflammatory process in AAV. Remission induction in patients with AAV continues to depend on the use of glucocorticoids (GC) in combination with rituximab or cyclophosphamide. Indeed, there are very limited treatment options and a clear need for strategies that reduce the use of GC without compromising efficacy. Avacopan is the first drug specifically developed for patients with AAV as its mechanism of action inhibits C5aR1, thus acting on one of the pathophysiological mechanisms of AAV. Keywords: Complement. Antineutrophil cytoplasmic antibodies-associated vasculitis. Avacopan. introduction ANCA-associated vasculitis (AAV) is a group of systemic autoimmune diseases characterized by necrotizing inflammation of small-caliber blood vessels. AAV include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA)1. The clinical presentation is heterogeneous. Renal (pauci-immune necrotizing glomerulonephritis), pulmonary (alveolar hemorrhage and lung nodules), and otorhinolaryngological (ENT) (nasal crusting, epistaxis, sinusopathy, and hearing loss) involvement, are very frequent2,3 . EGPA has clinical and pathological characteristics that differ from GPA and MPA. Therefore, the recommendations for its management also differ and have not been included in this review. AAV are characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA), the most common of which are those that directed against proteinase 3 (PR3) or myeloperoxidase (MPO)3. At present, the most accepted pathogenic pathway is based on the pathogenic nature of ANCA, which stimulate neutrophils with the consequent activation of the alternative complement pathway and production of C5a, an anaphylatoxin which plays a key role in amplifying the inflammatory process in AAV. C5a, through its binding to the C5aR1 receptor, attracts, and activates more neutrophils and increases vascular permeability, thus contributing to the injury produced in the blood vessel (Fig. 1)4,5 . In Spain, the estimated incidence of GPA is 2.1- 2.9 cases per million re

FAQs

What mechanism links ANCA to inflammation in ANCA-associated vasculitis?

ANCA stimulates neutrophils and activates the alternative complement pathway, resulting in C5a production. C5a then amplifies inflammation by recruiting and activating additional neutrophils and increasing vascular permeability.

Why are glucocorticoids still used for remission induction in AAV?

Remission induction depends on glucocorticoids combined with rituximab or cyclophosphamide. Limited treatment options create a need for strategies that reduce glucocorticoid use without reducing efficacy.

How does avacopan work in AAV treatment?

Avacopan inhibits the C5aR1 receptor, blocking a core pathophysiological mechanism in AAV. By targeting C5a signaling, it aims to control inflammation while potentially lowering glucocorticoid exposure.

Sep 25, 2026

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