Abstract: TH-PO0495
Early Real-World Biomarker Trajectories After Sibeprenlimab Initiation in Patients with IgAN: A Multicenter Observational Cohort Study
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - IgAN
October 22, 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
- Vasquez-Rios, George, Renal Medicine Associates, Albuquerque, New Mexico, United States
- Sanchez Russo, Luis F., Central Florida Kidney Specialists, Orlando, Florida, United States
- Hsu, Raymond K., University of California San Francisco School of Medicine, San Francisco, California, United States
- Kalra, Kartik, Geisinger Health, Danville, Pennsylvania, United States
- Udani, Suneel M., Nephrology Associates, Oak Park, Illinois, United States
- Geara, Abdallah Sassine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Oh, Wonsuk, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Campbell, Kirk N., University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Rajasekaran, Arun, Renal Medicine Associates, Albuquerque, New Mexico, United States
Background
Sibeprenlimab is the first APRIL-targeting monoclonal antibody approved for IgA nephropathy (IgAN), reducing pathogenic mucosal and B-cell–mediated immune activation. Real-world data regarding its use remains limited, particularly amongst multidrug therapeutic strategies.
Methods
We performed a multicenter real-world observational cohort study of biopsy-proven IgAN patients treated with sibeprenlimab. Study anchor (V0) was defined as first sibeprenlimab administration. Follow-up visits included V1 (4 weeks ±2), V2 (8 weeks ±2), and V3 (12–14 weeks ±3). Primary biomarkers included eGFR, UPCR, and UACR. Patients were categorized according to treatment context as: incidental/new initiation, sequential therapy after prior immune-modulator therapy, or add-on therapy to active treatment. Supportive therapies included RAAS blockers, sparsentan, atrasentan, and SGLT2i. UPCR and UACR were evaluated using geometric mean and percent-reduction analyses.
Results
15 patients (3 centers) with biopsy-proven IgAN were included. Mean age was 43±16 yrs, 53% were male, and 73% were ethnic minority. Mean baseline Sr Cr was 1.5±0.7 mg/dL and mean baseline eGFR was 58.7±28.4 mL/min/1.73m2. Median baseline UPCR was 2.9 g/g (IQR 1.8–4.6). Patients received multidrug supportive therapies, including sparsentan (53.3%), SGLT2i (60%), RAAS blockers (33.3%), and atrasentan (20%). Sequential therapy was common (53.3%). Progressive reductions in proteinuria were observed. Geometric mean UPCR decreased from 2.64 g/g at baseline to 1.88 g/g at V1, 1.41 g/g at V2, and 0.88 g/g at V3, corresponding to approximate reductions of 24.8%, 42.5%, and 58.7%, respectively. At V2, 57.1% achieved ≥30% UPCR reduction and 42.9% achieved ≥50% reduction. Albuminuria trajectories paralleled proteinuria improvement. There was no significant change in mean eGFR during follow-up. Adverse effects (URI & diarrhea among 4 patients) were generally mild and self-limited. Sibeprenlimab was not discontinued.
Conclusion
Sibeprenlimab initiation was associated with progressive early reductions in proteinuria and albuminuria in a real-world IgAN cohort receiving complex multidrug supportive regimens. These findings support the integration of APRIL inhibition into routine nephrology practice and highlight the evolving role of multidrug therapeutic strategies in IgAN management.