Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy
Jolijn R van Leeuwen,1 Luca Quartuccio,2 Juliana Bordignon Draibe,3 Iva Gunnarson,4 Ben Sprangers,5 Y K Onno Teng1 1Center of Expertise for Lupus-, Vasculitis- and Complement-Mediated Systemic Diseases (Luvacs), Department of Internal Medicine - Nephrology Section, Leiden University Medical Center,...
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Dove Medical Press
2025-01-01
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| author | van Leeuwen JR Quartuccio L Draibe JB Gunnarson I Sprangers B Teng YKO |
| author_facet | van Leeuwen JR Quartuccio L Draibe JB Gunnarson I Sprangers B Teng YKO |
| author_sort | van Leeuwen JR |
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| description | Jolijn R van Leeuwen,1 Luca Quartuccio,2 Juliana Bordignon Draibe,3 Iva Gunnarson,4 Ben Sprangers,5 Y K Onno Teng1 1Center of Expertise for Lupus-, Vasculitis- and Complement-Mediated Systemic Diseases (Luvacs), Department of Internal Medicine - Nephrology Section, Leiden University Medical Center, Leiden, the Netherlands; 2Division of Rheumatology, Department of Medicine, University of Udine, Udine, Italy; 3Department of Nephrology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; 4Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden; 5Department of Nephrology, Ziekenhuis Oost Limburg Genk, Genk, BelgiumCorrespondence: Y K Onno Teng, Department of Nephrology, Leiden University Medical Center (LUMC), P.O. Box 9600, Leiden, 2300 RC, the Netherlands, Tel +31-71-5262148, Fax +31-71-5266868, Email Y.K.O.Teng@lumc.nlAbstract: Recently, avacopan has been approved for the treatment of ANCA-associated vasculitis (AAV). Avacopan is an inhibitor of the C5a-receptor, which plays an important role in chemotaxis and the amplification loop of inflammation in AAV. In the most recent, international guidelines avacopan is recommended as steroid-sparing agents for the management of AAV. Here, we review the clinical trials that have led to demonstrate that avacopan is an effective treatment option in the management of AAV, where it can significantly reduce the cumulative dosage of glucocorticoids (GC). Despite the new guideline recommendations, clear guidance on how to employ avacopan in real-world clinical practice is lacking. We therefore also address in this review the data and clinical experience with avacopan obtained from real-world evidence. Combining preclinical studies, clinical trials, and real-world evidence helps to provide a better position of avacopan for the management of AAV in routine clinical practice, taking advantage of the GC-sparing effects of avacopan as a possible solution for the current challenge of reducing GC-toxicity in AAV patients. Furthermore, we delineate current knowledge gaps and future research areas that need to be addressed.Keywords: antineutrophil cytoplasmic antibody, ANCA, pauci-immune glomerulonephritis, complement, C5a inhibition, glucocorticoid toxicity |
| format | Article |
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| institution | Kabale University |
| issn | 1177-8881 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-3b3fd4eb45644117ae5c5917ddcd260e2025-01-05T16:36:04ZengDove Medical PressDrug Design, Development and Therapy1177-88812025-01-01Volume 19233798950Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapyvan Leeuwen JRQuartuccio LDraibe JBGunnarson ISprangers BTeng YKOJolijn R van Leeuwen,1 Luca Quartuccio,2 Juliana Bordignon Draibe,3 Iva Gunnarson,4 Ben Sprangers,5 Y K Onno Teng1 1Center of Expertise for Lupus-, Vasculitis- and Complement-Mediated Systemic Diseases (Luvacs), Department of Internal Medicine - Nephrology Section, Leiden University Medical Center, Leiden, the Netherlands; 2Division of Rheumatology, Department of Medicine, University of Udine, Udine, Italy; 3Department of Nephrology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; 4Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden; 5Department of Nephrology, Ziekenhuis Oost Limburg Genk, Genk, BelgiumCorrespondence: Y K Onno Teng, Department of Nephrology, Leiden University Medical Center (LUMC), P.O. Box 9600, Leiden, 2300 RC, the Netherlands, Tel +31-71-5262148, Fax +31-71-5266868, Email Y.K.O.Teng@lumc.nlAbstract: Recently, avacopan has been approved for the treatment of ANCA-associated vasculitis (AAV). Avacopan is an inhibitor of the C5a-receptor, which plays an important role in chemotaxis and the amplification loop of inflammation in AAV. In the most recent, international guidelines avacopan is recommended as steroid-sparing agents for the management of AAV. Here, we review the clinical trials that have led to demonstrate that avacopan is an effective treatment option in the management of AAV, where it can significantly reduce the cumulative dosage of glucocorticoids (GC). Despite the new guideline recommendations, clear guidance on how to employ avacopan in real-world clinical practice is lacking. We therefore also address in this review the data and clinical experience with avacopan obtained from real-world evidence. Combining preclinical studies, clinical trials, and real-world evidence helps to provide a better position of avacopan for the management of AAV in routine clinical practice, taking advantage of the GC-sparing effects of avacopan as a possible solution for the current challenge of reducing GC-toxicity in AAV patients. Furthermore, we delineate current knowledge gaps and future research areas that need to be addressed.Keywords: antineutrophil cytoplasmic antibody, ANCA, pauci-immune glomerulonephritis, complement, C5a inhibition, glucocorticoid toxicityhttps://www.dovepress.com/evaluating-avacopan-in-the-treatment-of-anca-associated-vasculitis-des-peer-reviewed-fulltext-article-DDDTantineutrophil cytoplasmic antibody (anca)pauci-immune glomerulonephritiscomplementc5a inhibitionglucocorticoid toxicity. |
| spellingShingle | van Leeuwen JR Quartuccio L Draibe JB Gunnarson I Sprangers B Teng YKO Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy Drug Design, Development and Therapy antineutrophil cytoplasmic antibody (anca) pauci-immune glomerulonephritis complement c5a inhibition glucocorticoid toxicity. |
| title | Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy |
| title_full | Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy |
| title_fullStr | Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy |
| title_full_unstemmed | Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy |
| title_short | Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy |
| title_sort | evaluating avacopan in the treatment of anca associated vasculitis design development and positioning of therapy |
| topic | antineutrophil cytoplasmic antibody (anca) pauci-immune glomerulonephritis complement c5a inhibition glucocorticoid toxicity. |
| url | https://www.dovepress.com/evaluating-avacopan-in-the-treatment-of-anca-associated-vasculitis-des-peer-reviewed-fulltext-article-DDDT |
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