Kidney Week

Abstract: TH-PO1254

Efficacy and Safety of B-Cell-Directed Therapies in IgA Nephropathy: A Collaborative Meta-Analysis

Session Information

• Late-Breaking Research Posters
  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

• Neuen, Brendon Lange, The George Institute for Global Health, Sydney, New South Wales, Australia

Brendon Lange Neuen, MBBS, MS, PhD, FASN

• Beal, Bryony A., The George Institute for Global Health, Sydney, New South Wales, Australia

Bryony A. Beal, MBBS

• Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom

Jonathan Barratt, MBChB, PhD

• Fletcher, Robert A., The George Institute for Global Health, Sydney, New South Wales, Australia

Robert A. Fletcher, MSc

• Campbell, Kirk N., University of Pennsylvania, Philadelphia, Pennsylvania, United States

Kirk N. Campbell, MD, FASN

• Lafayette, Richard A., Stanford University, Stanford, California, United States

Richard A. Lafayette, MD

• Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen, Groningen, GR, Netherlands

Hiddo Jan L. Heerspink, PharmD, PhD

• Lv, Jicheng, Peking University First Hospital, Beijing, China

Jicheng Lv, MD

• Rizk, Dana V., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States

Dana V. Rizk, MD

• Rovin, Brad, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad Rovin, MD, FASN

• Zhang, Hong, Peking University First Hospital, Beijing, China

Hong Zhang, MD, PhD

• Perkovic, Vlado, University of New South Wales, Sydney, New South Wales, Australia

Vlado Perkovic, MBBS, PhD, FASN

Group or Team Name

• CLARITY-IgAN Consortium

Background

B-cell dysfunction is central to the pathogenesis of IgA nephropathy (IgAN), with several therapies targeting galactose-deficient IgA1 immune complex formation being evaluated in late-phase clinical trials. However, the effects of these agents on key outcomes are incompletely characterised, as is their safety profile.

Methods

We conducted a collaborative meta-analysis of randomised, double-blind, placebo-controlled trials of B-cell directed therapies in patients with IgAN (PROPERO CRD42051218753). Published data were supplemented by information provided by investigators and sponsors. Efficacy outcomes included urinary protein:creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR) slope, and hematuria. Effects on serious adverse events, adverse events leading to treatment discontinuation, and infections were also evaluated.

Results

Eight trials including 1,599 participants were included. Mean age ranged from 37-42 years, 44% were female, and 68% were Asian. Mean baseline eGFR was 63-79 mL/min/1.73m2 and median UPCR was 1.25-1.40 g/g. B-cell directed therapies reduced UPCR by 50% (95% CI 46 to 54). Mean eGFR slope was –4.76 mL/min/1.73m²/year with placebo and +0.31 mL/min/1.73m²/year with B-cell directed therapies (difference 4.85 mL/min/1.73m²/year, 95% CI 4.05-5.64; Figure 1). B-cell directed therapies also increased the likelihood of hematuria resolution (RR 3.88, 95% CI 2.61-5.77). Serious adverse events (RR 0.57, 95% CI 0.38-0.83) and adverse events leading to treatment discontinuation (RR 0.45, 95% CI 0.27-0.77) were less frequent with B-cell directed therapies than with placebo, with no increased risk of infections (RR 1.04, 95% CI 0.91-1.19).

Conclusion

In patients with IgAN, B-cell directed therapies reduced proteinuria, hematuria, and effectively halted kidney function decline, without increasing the risk of serious adverse events or infections. These findings support B-cell-directed therapies as the preferred first-line disease-modifying therapy in this population.

Effect of B-cell therapies on eGFR slope in IgA nephropathy.