Skip to main content
SpringerLink
Log in

Avacopan, a Novel Competitive C5a Receptor Antagonist, for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

  • Review Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Avacopan is a relatively novel drug with complement antagonizing properties, and it has demonstrated promising outcomes in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. This review article seeks to investigate the current standard of care for ANCA vasculitis with the combination of avacopan. The current standard therapy involves the usage of daily corticosteroids in addition to either cyclophosphamide or rituximab; however, prolonged use of corticosteroids is known to be associated with various adverse effects. Avacopan was introduced as a possible substitution to alleviate high-corticosteroid dosages. It functions through competitive inhibition of the C5a receptor in the complement system and results in the reduction of neutrophil activation and migration to sites of inflammation. Clinical trials have observed the efficacy of avacopan both in conjunction with standard therapy with corticosteroids and without corticosteroids. The use of avacopan was able to achieve disease remission and improve renal function in patients with ANCA-associated vasculitis. Additionally, the novel treatment did not increase the risk of adverse events during treatment, while also lowering the toxic effects associated with corticosteroid usage. In summary, current evidence supports the success and safety of administering avacopan to treat patients with ANCA-associated vasculitis. Additional clinical trials are warranted to identify optimal dosage and method in using avacopan in the clinical setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jennette JC. Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013;17(5):603–6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Geetha D, Jefferson JA. ANCA-associated vasculitis: core curriculum 2020. Am J Kidney Dis. 2020;75(1):124–37.

    Article  CAS  PubMed  Google Scholar 

  3. Charles Jennette J, Falk RJ. L1. Pathogenesis of ANCA-associated vasculitis: observations, theories and speculations. La Presse Médicale. 2013;42(4):493–8.

    Article  CAS  PubMed  Google Scholar 

  4. Almaani S, Fussner LA, Brodsky S, Meara AS, Jayne D. ANCA-associated vasculitis: an update. JCM. 2021;10(7):1446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Flossmann O, Berden A, De Groot K, Hagen C, Harper L, Heijl C, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70(3):488–94.

    Article  PubMed  Google Scholar 

  6. King C, Harper L. Avoidance of harm from treatment for ANCA-associated vasculitis. Curr Treat Options Rheumatol. 2017;3(4):230–43.

    Article  Google Scholar 

  7. Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. 2011;69(6): 1036.

    Article  Google Scholar 

  8. Gou SJ, Yuan J, Chen M, Yu F, Zhao MH. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis. Kidney Int. 2013;83(1):129–37.

    Article  CAS  PubMed  Google Scholar 

  9. Huugen D, Van Esch A, Xiao H, Peutz-Kootstra CJ, Buurman WA, Tervaert JWC, et al. Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice. Kidney Int. 2007;71(7):646–54.

    Article  CAS  PubMed  Google Scholar 

  10. FDA approves add-on drug for adults with rare form of blood vessel inflammation [Internet]. Food and Drug Administration; 2021. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-drug-adults-rare-form-blood-vessel-inflammation.

  11. Hamour S, Salama AD, Pusey CD. Management of ANCA-associated vasculitis: current trends and future prospects. Ther Clin Risk Manag. 2010;6:253–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Walsh M, Merkel PA, Peh CA, Szpirt WM, Puéchal X, Fujimoto S, et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020;382(7):622–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chung SA, Langford CA, Maz M, Abril A, Gorelik M, Guyatt G, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis Care Res. 2021;73(8):1088–105.

    Article  Google Scholar 

  14. Samman KN, Ross C, Pagnoux C, Makhzoum JP. Update in the management of ANCA-associated vasculitis: recent developments and future perspectives. Int J Rheumatol. 2021;2021:1–14.

    Article  Google Scholar 

  15. Shi L. Anti-neutrophil cytoplasmic antibody-associated vasculitis: prevalence, treatment, and outcomes. Rheumatol Int. 2017;37:1779–88.

    Article  CAS  PubMed  Google Scholar 

  16. Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359(26):2790–803.

    Article  CAS  PubMed  Google Scholar 

  17. Jones RB, Hiemstra TF, Ballarin J, Blockmans DE, Brogan P, Bruchfeld A, et al. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann Rheum Dis. 2019;78(3):399–405.

    Article  CAS  PubMed  Google Scholar 

  18. Trivioli G, Vaglio A. The rise of complement in ANCA-associated vasculitis: from marginal player to target of modern therapy. Clin Exp Immunol. 2020;202(3):403–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xiao H, Dairaghi DJ, Powers JP, Ertl LS, Baumgart T, Wang Y, et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol. 2014;25(2):225–31.

    Article  CAS  PubMed  Google Scholar 

  20. Söderberg D, Segelmark M. Neutrophil extracellular traps in ANCA-associated vasculitis. Front Immunol. 2016;7:256.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lee A. Avacopan: first approval. Drugs. 2022;82(1):79–85.

    Article  CAS  PubMed  Google Scholar 

  22. Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L, et al. Characterization of Pharmacologic and pharmacokinetic properties of CCX168, a potent and selective orally administered complement 5a receptor inhibitor, based on preclinical evaluation and randomized phase 1 clinical study. PLoS One. 2016;11(10): e0164646.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gastoldi S, Charo IF, Dairaghi D, Bekker P, Schall TJ, Benigni A, et al. Inhibition of the c5a receptor by CCX168 markedly reduces the thrombogenic potential of serum from patients with atypical hemolytic uremic syndrome. Nephrol Dial Transplant. 2015;30(suppl 3): iii382.

    Article  Google Scholar 

  24. Jayne DRW, Merkel PA, Schall TJ, Bekker P, ADVOCATE Study Group. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384(7):599–609.

    Article  CAS  PubMed  Google Scholar 

  25. Huizenga N, Zonozi R, Rosenthal J, Laliberte K, Niles JL, Cortazar FB. Treatment of aggressive antineutrophil cytoplasmic antibody-associated vasculitis with eculizumab. Kidney Int Rep. 2020;5(4):542–5.

    Article  PubMed  Google Scholar 

  26. Łyczko K, Borger J. Meningococcal prophylaxis [Updated 2023 May 1]. Treasure Island: StatPearls Publishing [Internet]; 2023. https://www.ncbi.nlm.nih.gov/books/NBK537338/.

  27. Jayne DRW, Bruchfeld AN, Harper L, Schaier M, Venning MC, Hamilton P, et al. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J Am Soc Nephrol. 2017;28(9):2756–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Merkel PA, Niles J, Jimenez R, Spiera RF, Rovin BH, Bomback A, et al. Adjunctive treatment with avacopan, an oral C5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody–associated vasculitis. ACR Open Rheumatol. 2020;2(11):662–71.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Jayne DRW, Merkel PA, Schall TJ, Bekker P. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384(7):599–609.

    Article  CAS  PubMed  Google Scholar 

  30. Ennis D, Yeung RS, Pagnoux C. Long-term use and remission of granulomatosis with polyangiitis with the oral C5a receptor inhibitor avacopan. BMJ Case Rep. 2020;13(10): e236236.

    Article  PubMed  PubMed Central  Google Scholar 

  31. van Leeuwen JR, Bredewold OW, van Dam LS, Werkman SL, Jonker JT, Geelhoed M, et al. Compassionate use of avacopan in difficult-to-treat antineutrophil cytoplasmic antibody-associated vasculitis. Kidney Int Rep. 2021;7(3):624–8.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Alvarez L, Kambham N, Su R. Renal improvement and remission in a patient with refractory ANCA-associated vasculitis treated with avacopan. J Nephrol [Internet]. 2023. https://doi.org/10.1007/s40620-023-01614-y.

    Article  PubMed  Google Scholar 

  33. Gabilan C, Pfirmann P, Ribes D, Rigothier C, Chauveau D, Casemayou A, et al. Avacopan as first-line treatment in antineutrophil cytoplasmic antibody-associated vasculitis: a steroid-sparing option. Kidney Int Rep. 2022;7(5):1115–8.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, LSU Health Sciences Center New Orleans, 1901 Gravier Street, New Orleans, LA, 70112, USA

    Ivan D. Nguyen, Evan S. Sinnathamby, Joseph Mason & Bretton Urban

  2. School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA

    Elisa E. Neuchat

  3. University of Arizona College of Medicine-Phoenix, 475 N 5th St, Phoenix, AZ, 85004, USA

    Danielle M. Wenger

  4. Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA

    Shahab Ahmadzadeh, Sahar Shekoohi & Alan D. Kaye

  5. Department of Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA

    Alan D. Kaye

Authors
  1. Ivan D. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evan S. Sinnathamby
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph Mason
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bretton Urban
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisa E. Neuchat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Danielle M. Wenger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shahab Ahmadzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sahar Shekoohi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alan D. Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sahar Shekoohi.

Ethics declarations

Funding

No funding or sponsorship was received for this study or publication of this article.

Conflict of interest

Ivan D. Nguyen, Evan S. Sinnathamby, Joseph Mason, Bretton Urban, Elisa E. Neuchat, Danielle M. Wenger, Shahab Ahmadzadeh, Sahar Shekoohi and Alan D. Kaye have no conflicts of interest.

Author contributions

All authors listed have made a direct and intellectual contribution to the work and approved for publication.

Ethics approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Code availability

Not applicable.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nguyen, I.D., Sinnathamby, E.S., Mason, J. et al. Avacopan, a Novel Competitive C5a Receptor Antagonist, for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Clin Drug Investig 43, 595–603 (2023). https://doi.org/10.1007/s40261-023-01298-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-023-01298-z

Search

Navigation