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Kidney Week

Abstract: SA-OR049

Ravulizumab in Atypical Hemolytic Uremic Syndrome: Time-to-Treatment Analysis from a Phase 3 Trial

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Garlo, Katherine, Alexion, AstaZeneca Rare Disease, Boston, Massachusetts, United States
  • Greenbaum, Larry A., Division of Pediatric Nephrology, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia, United States
  • Dixon, Bradley P., Renal Section, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States
  • Kavanagh, David, National Renal Complement Therapeutics Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Translational and Clinical Research Institute, Newcastle University, Newcastle, United Kingdom
  • Kang, Hee Gyung, Division of Pediatric Nephrology, Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Chen, Joyce, Alexion, AstaZeneca Rare Disease, Boston, Massachusetts, United States
  • Ogawa, Masayo, Alexion, AstaZeneca Rare Disease, Boston, Massachusetts, United States
  • Cataland, Spero R., Division of Hematology, The Ohio State University Medical Center, Columbus, Ohio, United States
  • Luque, Yosu, Renal Intensive Care Unit, Nephrology Department, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
  • Taylor, Veronica, Division of Pediatric Nephrology, University of Nebraska Medical Center, Children’s Nebraska, Omaha, Nebraska, United States
  • Miyakawa, Yoshitaka, Department of Hematology, Saitama Medical University, Saitama, Japan
Background

Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Previous studies have demonstrated that earlier diagnosis and treatment initiation lead to better outcomes. There is limited data demonstrating this with ravulizumab (RAV), a complement C5 inhibitor (C5i) approved for the treatment of aHUS.

Methods

This analysis reports data from the 4.5-year extension period of a phase 3, single-arm clinical trial of C5i-naive adult patients (pts) with aHUS (NCT02949128). Pts received body-weight–based intravenous RAV every 4–8 weeks. The primary endpoint was complete TMA response at Week (Wk) 26. A time-to-treatment post hoc analysis was performed and grouped by ≤7 days (d) or >7d from time of first aHUS symptom to initiating RAV.

Results

56 pts were analyzed: 24 in the ≤7d group and 32 in the >7d group. There were no substantial differences between the groups according to age at first infusion and sex. Complete TMA response was observed in the ≤7d group in 16/24 pts (67%) at Wk 26 and 18/24 (75%) by end of study; in the >7d group in 14/32 pts (44%) at Wk 26 and 18/32 (56%) by end of study. Mean change in estimated glomerular filtration rate (eGFR) from baseline was higher for pts in the ≤7d group than in the >7d group (Figure). In the ≤7d group, 15/24 pts (63%) were on dialysis at baseline and 4/22 (18%) at Wk 26; in the >7d group, 14/32 pts (44%) were on dialysis at baseline and 8/27 (30%) at Wk 26.

Conclusion

Earlier RAV initiation led to improved outcomes, including reduced dialysis requirements, which demonstrates the importance of rapid diagnosis and treatment of pts with aHUS.

Funding

  • Commercial Support – Alexion, AstraZeneca Rare Disease

Digital Object Identifier (DOI)