Kidney Week

Abstract: SA-PO805

Safety and Effectiveness of Switching to Ravulizumab from Eculizumab in Kidney Transplant Recipients with Atypical Hemolytic Uremic Syndrome: A Global Registry Analysis

Session Information

• C3G, TMA, MGRS, Amyloidosis, and More
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Gaeckler, Anja H., University Hospital Essen, University Duisburg-Essen, Essen, Germany

Anja H. Gaeckler, MD

• Al-Dakkak, Imad, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Imad Al-Dakkak

• Saval, Nuria, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Nuria Saval, MD

• Dieperink, Hans Herman, Odense University Hospital, Odense, Denmark

Hans Herman Dieperink, MD, DrMed

• Eygenraam, Margriet, aHUS Canada, Brampton, Brampton, Ontario, Canada

Margriet Eygenraam

• Greenbaum, Larry A., Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia, United States

Larry A. Greenbaum, MD, PhD

• Isbel, Nicole, The University of Queensland and Princess Alexandra Hospital, Brisbane, Queensland, Australia

Nicole Isbel, MBBS, PhD

• Vande Walle, Johan, Ghent University Hospital, Gent, Belgium

Johan Vande Walle, MD, PhD

Background

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation that causes kidney failure and has a propensity to recur after kidney transplant (KTx) with graft loss. Ravulizumab (RAV) and eculizumab (ECU) are C5 inhibitors approved for the treatment of aHUS. We assessed the real-world safety and effectiveness of switching from ECU to RAV in KTx recipients with aHUS for immediate, complete, and sustained terminal complement inhibition.

Methods

The Global aHUS Registry is a multicenter study (NCT01522183) enrolling patients (pts) with aHUS since 2012. Safety and effectiveness outcomes were assessed in KTx recipients with aHUS who switched from ECU to RAV up to April 22, 2024. Safety analyses included pts with a KTx before RAV initiation; pt characteristic and effectiveness analyses included KTx recipients who received RAV for ≥3 months and had ≤1 month between ECU discontinuation and RAV initiation.

Results

Overall, 29 pts (25 adults) were included in safety analyses; 21 adverse events (AEs) were reported in 15 pts at or after RAV initiation, and none were unexpected. During RAV treatment, no new AEs of thrombotic microangiopathy or kidney impairment, and no meningococcal infections or deaths were reported. Among 21 pts (20 adults) included in the pt characteristic and effectiveness analyses, median (range) age at RAV initiation was 35 (11–72) years, and 67% had a reported pathogenic complement variant or anti-complement factor H antibodies. Median (range) time on treatment was 66 (4–158) months for ECU and 24 (5–43) months for RAV; median (range) time from last KTx to RAV initiation was 56 (4–184) months. Mean (standard deviation) estimated glomerular filtration rate was 50 (25) mL/min/1.73m² at last record before or at RAV initiation and 50 (28) mL/min/1.73m² at last follow-up after RAV initiation. Among 29 KTx events in these 21 pts, no rejections or graft failures were reported after RAV initiation.

Conclusion

This analysis from the Global aHUS Registry provides real-world evidence of the successful transition from ECU to RAV in KTx recipients with aHUS, with stable kidney function and no unexpected safety concerns.

Funding

• Commercial Support – Alexion, AstraZeneca Rare Disease