Abstract: SA-PO0678
Comparative Effectiveness of Complement-Targeted Therapies for C3 Glomerulopathy: A Systematic Review and Bayesian Network Meta-Analysis
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Kaskinen, Anu, Department of Paediatrics, Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
- Khandelwal, Priyanka, Department of Paediatrics, Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
- Jauhal, Arenn Singh, Department of Medicine, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
- Patriquin, Christopher J., Department of Medicine, Division of Haematology, University of Toronto, Toronto, Ontario, Canada
- Licht, Christoph, Department of Paediatrics, Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
- Robinson, Cal, Department of Paediatrics, Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada
Background
C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare complement-mediated kidney diseases associated with progressive kidney disease. Recent trials demonstrated efficacy of complement-targeted therapies in C3G and IC-MPGN. However, direct comparative evidence between agents is lacking. We performed a Bayesian network meta-analysis to compare efficacy and safety of complement-targeted therapies.
Methods
Randomized clinical trials (RCT) evaluating complement-targeted therapies in C3G and IC-MPGN were identified through systematic searches of MEDLINE, Embase, CENTRAL, and major nephrology conference proceedings through December 2025. Outcomes included relative change in proteinuria at 6 months as primary outcome, estimated glomerular filtration rate (eGFR), C3 histologic index (C3HI), and adverse events. Treatment effects were estimated using Bayesian models and ranked by surface under the cumulative ranking curve (SUCRA). Sensitivity analyses were performed using random-effects models. Risk of bias was evaluated using the Cochrane RoB 2.0 tool. The protocol was registered in PROSPERO (CRD420251250384).
Results
A total of four RCTs including 265 patients and evaluating pegcetacoplan, iptacopan, avacopan, and danicopan were included. Compared with placebo/supportive care pegcetacoplan demonstrated the greatest proteinuria reduction of -68.6% (95% credible interval [CrI], -83.2 to -54.0, iptacopan reduced proteinuria by -38.3% (95% CrI, -63.6 to -13.1), avacopan and danicopan showed smaller and more variable effects. Pegcetacoplan was ranked highest for proteinuria reduction (SUCRA 0.97) and iptacopan second (0.66). Sensitivity analyses attenuated indirect treatment effects, but rankings remained stable. Changes in eGFR over 6 months were modest and did not differ significantly between therapy groups. No therapy significantly improved C3HI. Safety profiles were comparable across treatments.
Conclusion
Pegcetacoplan and iptacopan achieved early proteinuria reduction in C3G and IC-MPGN, whereas effects on short-term kidney function were modest. Differences between leading therapies remained uncertain, although pegcetacoplan ranked highest overall. These findings may inform management of C3G and IC-MPGN but highlight the need for longer-term comparative studies.