EULAR, the European Alliance of Associations for Rheumatology, has released updated guidelines for treating and managing ANCA-associated vasculitis (AAV), including the addition of new steroid-sparing treatments.[1] In the announcement, EULAR notes that several clinical trials have been completed since the previous guidelines published in 2016, which potentially change clinical care best practice.

The EULAR recommendations for the management of AAV aim to provide practical, evidence-based recommendations for the diagnosis and treatment of AAV, thereby improving and harmonizing standards of diagnosis and treatment, and potentially improving the quality of care. In updating the recommendations, a EULAR task force undertook a systematic literature review and sought the opinions of 20 experts from 16 countries.

One of the key trials the group highlights is the ADVOCATE trial, which evaluated whether avacopan could replace a glucocorticoid-tapering regimen used in the treatment of ANCA-associated vasculitis.[2,3] Glucocorticoid-induced toxic effects were a key secondary endpoint, as measured by the Steritas Glucocorticoid Toxicity Index (GTI).[4] The trial led to the approval of Tavneos™ (avacopan) as an add-on treatment for ANCA-associated vasculitis.

Commenting on the announcement, Martha Stone, CEO of Steritas said: 

“It is extremely gratifying to see that a steroid-sparing agent, approved with the help of the Steritas GTI, is now part of European guidelines for the management of ANCA-associated vasculitis (AAV).”

The new guidelines include the following key recommendations:

• For remission induction in life-threatening or organ-threatening ANCA-associated vasculitis, EULAR now recommends a combination of high-dose glucocorticoids in combination with either rituximab or cyclophosphamide. 
• Tapering of glucocorticoid dose to a target of 5 mg prednisolone equivalent/day is advised within 4 to 5 months. 
• Avacopan may be considered as part of a strategy to reduce exposure to glucocorticoids in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

The guidelines were also welcomed by Fabio Dorigotti, Head Global Medical Affairs of CSL Vifor, the European licensee of Tavenos: 

"We are very pleased with the new AAV management recommendations and are grateful for this development for patients living with this systemic condition.

We are confident that the updated recommendations will further strengthen the role of Tavneos® in the management of AAV patients to achieve remission, with the potential to improve renal function while reducing the exposure and toxic effects associated with the prolonged use of high-dose glucocorticoids."

The updated guidelines from EULAR follow similar revisions to guidelines made in 2021 by the American College of Rheumatology and The Vasculitis Foundation. These guidelines also recommended steroid-sparing therapies such as rituximab or cyclophosphamide. However, as the ACR updates occurred before the approval of avacopan, they did not include the drug in their recommendations, but did highlight the positive nature of the ADVOCATE clinical trial. [5]

REFERENCES

1. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update Annals of the Rheumatic Diseases 16 March 2023. doi: 10.1136/ard-2022-223764
2. Jayne DRW, Merkel PA, Schall TJ, Bekker P; ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. http://doi.org/10.1056/NEJMoa2023386.
3. Steritas; https://www.steritas.com/clinical-avacopan-data
4. Stone, J.H et al. The glucocorticoid toxicity index: Measuring change in glucocorticoid toxicity over time, Seminars in Arthritis and Rheumatism, Volume 55, 2022, 152010, https://doi.org/10.1016/j.semarthrit.2022.152010.
5. Chung SA, et al. 2021 American College of Rheumatology/Vasculitis Foundation; Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken). 2021 Aug;73(8):1088-1105. doi: 10.1002/acr.24634.