Abstract: SA-PO0675
Efficacy and Safety of Targeted Complement Inhibitors in Patients with C3 Glomerulopathy: A Systematic Review and Quantitative Synthesis of Randomized Controlled Trials
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
- Bouhuwaish, Ahmad, Tobruk University, Tobruk, Butnan District, Libya
- Sakran, Shahd Husayn, Tobruk University, Tobruk, Butnan District, Libya
- Bouhuwaish, Sarah Elmabri, Tobruk University, Tobruk, Butnan District, Libya
- Mohamed, Muner, Ochsner Health, New Orleans, Louisiana, United States
Group or Team Name
- Ochsner Nephrology
Background
C3 glomerulopathy (C3G) is a rare condition characterized by kidney damage after deposition of C3 in the kidney glomeruli. Although the conventional treatment includes general supportive therapy, the recent advent of specific inhibitors of the complement components (C3, Factor B, and C5a) may help to revolutionize C3G treatment strategies. This systematic review and meta-analysis aim to assess the efficacy and safety of new complement inhibitors in the context of renal function stabilization and proteinuria reduction
Methods
Databases of PubMed, Embase, CENTRAL, Scopus and ClinicalTrials.gov were systematically examined up until April 2026. Phase 2-3 randomized controlled trials (RCTs) investigating iptacopan, pegcetacoplan, or avacopan in adolescent and adults suffering from C3G diagnosed by biopsy were selected. The primary outcome of interest was the degree of proteinuria reduction (UPCR) and estimated glomerular filtration rate change (eGFR). Random-effect models were employed for data synthesis with sensitivity analyses to adjust for individual study variance
Results
Meta-analysis of three randomized controlled trials (APPEAR-C3G, VALIANT, and ACCOLADE) with 255 participants revealed that complement inhibitors provide a clinical benefit in managing C3G. The first pooled analysis of all three trials demonstrated a relative reduction in proteinuria by 41.7% (p=0.09); however, this result became more convincing after exclusion of the negative trial ACCOLADE. The latter showed a significant reduction in proteinuria of 54.6%( p=0.03) compared to control, confirming the efficacy of complement inhibitors in this indication. Moreover, apart from protein reduction, therapy significantly preserved renal function with a mean increase in eGFR of (3.91) mL/min/1.73m relative to placebo (p=0.02) At the same time, the beneficial effects were achieved without any sacrifice of patient safety. There was no difference in the incidence of severe adverse events (RR 1.10) or withdrawal from treatment due to side effects.
Conclusion
From the recent research conducted in our study, it is evident that complement inhibitors are an effective method that can be employed in managing C3 glomerulopathy (C3G), particularly proteinuria reduction. However, additional research is still required to validate this Results