Background/ Objectives: Avacopan is a new, promising treatment for ANCA-associated vasculitis (AAV) and can potentially replace steroids. Compared to steroid tapering, avacopan has demonstrated non-inferiority for treatment response at 26 weeks, superiority for sustaining remission at 52 weeks and a reduction of relapses.¹ Most recently avacopan was approved for the treatment of AAV by the U.S. Food and ug Administration and approval is pending at the European Medicines Agency (EMA).² We now report the (...)

Background/ Objectives: Avacopan is a new, promising treatment for ANCA-associated vasculitis (AAV) and can potentially replace steroids. Compared to steroid tapering, avacopan has demonstrated non-inferiority for treatment response at 26 weeks, superiority for sustaining remission at 52 weeks and a reduction of relapses.¹ Most recently avacopan was approved for the treatment of AAV by the U.S. Food and ug Administration and approval is pending at the European Medicines Agency (EMA).² We now report the first clinical experience with avacopan in difficult-to-treat AAV patients in the setting of a compassionate use program.

Methods: We collected disease relevant characteristics for the adult AAV patients who were treated with avacopan in the setting of the compassionate use program at the department of Nephrology of the Leiden University Medical Center. Patients were classified by their reason to start avacopan and clinical remission was based on physician’s clinical assessments as reported in the electronic health records. We collected relevant data to assess steroid-related toxicity effects in line with the Glucocorticoid Toxicity Index (GTI) (v2017).³

Results: Eight adult AAV patients were treated within the avacopan compassionate use program at our institute. Indications for avacopan were steroid resistance (n=4), steroid dependence (n=2) and high risk of steroid toxicity (n=2). Most patients had relapsing disease (numbers of flares ranging from 0-3) and received multiple previous remission induction therapies (median 2, range 1-6). All patients achieved clinical remission within six months after avacopan was started. Only one patient experienced a major flare, which coincided with a reduction of avacopan dosing to 20mg bd due to delayed supply during the COVID-19 pandemic. Steroid tapering was successful in all patients, with five patients discontinuing prednisone and three patients continuing low doses of prednisolone (2.5-7.5mg/day). After one year of avacopan use, the GTI improved in four patients. In one patient the GTI worsened due to weight gain. Six patients satisfactorily continue avacopan and are persistently in clinical remission. One patient stopped because of a pregnancy wish.

Conclusions: We here provide the first real-life practice observations on the compassionate use of avacopan in difficult-to-treat AAV patients. Avacopan demonstrated added-value in the treatment of our difficult-to-treat AAV cases with respect to improved disease control, reduced steroid dependence and reduced steroid-related toxicity.

Disclosures: The work of YKOT was supported by the Dutch Kidney Foundation (17OKG04) and by the Arthritis Research and Collaboration Hub (ARCH) foundation. ARCH is funded by Dutch Arthritis Foundation (ReumaNederland). YKOT received an unrestricted research grant and consultancy fees from Vifor Pharma.

References

1.         Jayne, D.R.W., et al., Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med, 2021. 384(7): p. 599-609.

2.         ANCA vasculitis News. FDA Approves Tavneos as Add-on Therapy for Severe MPA, GPA. Published October 11, 2021. Accessed October 29, 2021.  https://ancavasculitisnews.com/2021/10/11/fda-approves-tavneos-avacopan-add-on-mpa-gpa-therapy/

3.         Miloslavsky, E.M., et al., Development of a Glucocorticoid Toxicity Index (GTI) using multicriteria decision analysis. Ann Rheum Dis, 2017. 76(3): p. 543-546.