Kidney Week

Abstract: SA-PO872

Avacopan in Combination with Rituximab and Low-Dose Cyclophosphamide for Treatment of Severe ANCA-Associated Glomerulonephritis

Session Information

• Glomerular Diseases: Therapeutics
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Dhutia, Amrita, Imperial College Healthcare NHS Trust, London, United Kingdom

Amrita Dhutia,

• Prendecki, Maria, Imperial College London, London, London, United Kingdom

Maria Prendecki,

• Shuaib, Fathima Rishana, Imperial College Healthcare NHS Trust, London, United Kingdom

Fathima Rishana Shuaib,

• Condon, Marie B., Imperial College Healthcare NHS Trust, London, United Kingdom

Marie B. Condon,

• Griffith, Megan, Imperial College London, London, United Kingdom

Megan Griffith,

• Levy, Jeremy B., Imperial College London, London, United Kingdom

Jeremy B. Levy,

• Medjeral-Thomas, Nicholas R., Imperial College London, London, United Kingdom

Nicholas R. Medjeral-Thomas,

• Nikolopoulou, Lina, Imperial College Healthcare NHS Trust, London, United Kingdom

Lina Nikolopoulou,

• Cairns, Tom, Imperial College Healthcare NHS Trust, London, United Kingdom

Tom Cairns,

• McAdoo, Stephen Paul, Imperial College London, London, United Kingdom

Stephen Paul McAdoo,

Background

Avacopan is approved in the USA and Europe as a novel treatment for ANCA-associated vasculitis. There are limited data regarding avacopan use in those with severe renal disease, and of ‘real-world’ experience using avacopan in combination remission-induction regimens.

Methods

Prospective cohort study of patients with ANCA-associated glomerulonephritis (ANCA-GN) treated at a single centre in London, UK from December 2022. Data presented as median (+/- IQR) unless otherwise stated.

Results

To date, 27 patients with ANCA-GN have received avacopan (median age 58 years [range 24-90]; 22 de novo disease, 5 relapsing).
Baseline parameters: BVAS 16 (IQR 12-19), CRP 61mg/dL (21-174), creatinine 258µmol/L (149-391), eGFR 19ml/min/1.73m² (12-39), uPCR 164mg/mmol (6-216). 21 patients had confirmatory kidney biopsy, with no predominant Berden class.
Immunosuppressive treatment: 23 patients received combination induction treatment with rituximab (2g) and low-dose IV cyclophosphamide (median dose 2.2g [1.0-2.5]); 4 were treated with rituximab alone; 8 received adjunctive plasma exchange.
Glucocorticoid (GC) use: The median dose of IV methylprednisolone was 0mg (0-500). 25/27 patients received oral prednisolone with median dose and duration of 270mg (210-420) and 8 days (7-16), respectively.
Outcomes: The median duration of follow up is currently 2 months: 26/27 have achieved disease remission (BVAS =0; 1 patient had progressive eGFR decline). Improvements in renal parameters were as follows: creatinine 152µmol/L (125-257), eGFR 37ml/min/1.73m² (23-48), uPCR 42mg/mmol (15-281). In those who presented with eGFR ≤20ml/min/1.73m² (n=15), median eGFR improved from 13 (9-18) to 27 (12-39).
Adverse Events: 2 infections occurred (uncomplicated UTI treated with oral antibiotics; LRTI requiring IV antibiotics). 1 patient developed transaminitis requiring drug cessation.

Conclusion

This early series suggests that avacopan is well-tolerated and facilitates GC minimisation in patients with active ANCA-GN, in a non-trial setting, and in combination with rituximab and low-dose cyclophosphamide. Renal recovery was favourable in those presenting with eGFR ≤20ml/min/1.73m^2. Ongoing analysis will examine long-term renal recovery in this subgroup.