Abstract: PO1851
Comparative Efficacy of Ravulizumab and Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome: An Indirect Comparison Using Clinical Trial Data
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Trials - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Rondeau, Eric, Hôpital Tenon, APHP and Sorbonne Université, Paris, France
- Hatswell, Anthony J., Delta Hat Limited, Nottingham, United Kingdom
- Cataland, Spero R., Ohio State University, Columbus, Ohio, United States
- Chen, Peter, Alexion Pharmaceuticals Inc., Boston, Massachusetts, United States
- Freemantle, Nicholas, University College London, London, United Kingdom
- Myren, Karl-Johan, Alexion Pharmaceuticals Inc., Boston, Massachusetts, United States
- Lommele, Asa, Alexion Pharmaceuticals Inc., Boston, Massachusetts, United States
- Wang, Yan, Alexion Pharmaceuticals Inc., Boston, Massachusetts, United States
- Deighton, Kevin, Delta Hat Limited, Nottingham, United Kingdom
- Knowles, Emma, Delta Hat Limited, Nottingham, United Kingdom
- Sheerin, Neil S., Newcastle University, Newcastle, United Kingdom
- Tomazos, Ioannis, Alexion Pharmaceuticals Inc., Boston, Massachusetts, United States
Background
Atypical hemolytic uremic syndrome (aHUS) is a rare disease that can cause organ damage or death if not suitably treated. Eculizumab (ECU), a C5 inhibitor, was approved to treat aHUS in 2011. Ravulizumab (RAV), approved in 2019, was engineered from ECU to reduce dosing frequency (every 8 weeks [for patients weighing ≥20 kg] vs 2 weeks, respectively) and minimise treatment burden. Both drugs have established safety and efficacy via pivotal single armed studies. We indirectly compared the efficacy of RAV vs ECU using clinical trial data.
Methods
Patient-level data from a pivotal RAV trial (NCT02949128) and pivotal ECU trials (NCT00844428, NCT01194973) for adults with aHUS without kidney transplant were used. Propensity scores were calculated based on baseline characteristics (dialysis status, estimated glomerular filtration rate [eGFR], platelet count and serum lactate dehydrogenase), with stabilized inverse probability weighting used to balance groups while preserving sample size. Outcomes were changes in clinical characteristics at 26 weeks, and evaluated between groups using appropriate statistical tests at a 5% significance level.
Results
In all, 85 patients (46 RAV, 39 ECU) were included for analysis. Baseline characteristics were balanced after weighting, with no significant difference between groups in any clinical or patient-reported characteristics. At 26 weeks, outcomes were improved from baseline in both groups, including reduced prevalence of dialysis, and increased mean eGFR and mean platelet count, with no significant differences between groups (Table).
Conclusion
After balancing patient characteristics between study groups, no significant differences were seen between outcomes for ECU and RAV at 26 weeks.
Representative clinical characteristics at baseline and 26 weeks.
| Clinical characteristic | Patients receiving ravulizumab (n=46)* | Patients receiving eculizumab (n=39) | P value | Differences between groups (95% confidence interval) |
| Patients receiving dialysis (%) At baseline At 26 weeks | 52 22 | 53 8 | 0.998 0.070 | 0 (-21 to 21) -15 (-30 to 1) |
| eGFR (mL/min/1.73m2; mean [SD])† At baseline At 26 weeks | 16.7 (16.6) 55.4 (40.8) | 16.6 (12.4) 51.4 (30.8) | 0.996 0.619 | 0.0 (-6.3 to 6.3) -4.0 (-19.8 to 11.8) |
| Patients experiencing an improvement of ≥15 mL/min/1.73m2 in eGFR from baseline at 26 weeks (%) | 59 | 64 | 0.662 | 5 (-16 to 26) |
| Platelet count (x109/L; mean [SD]) At baseline At 26 weeks | 118 (85) 243 (81) | 118 (65) 244 (65) | 0.979 0.953 | 0 (-33 to 32) 1 (-31 to 33) |
*For eGFR and platelet count, n=43 at 26 weeks. †eGFR defined as 10 mL/min/1.73m2 for those on dialysis.
Funding
- Commercial Support – This study was sponsored by Alexion Pharmaceuticals, Inc.