Obinutuzumab Shows Durable Kidney Protection and High Remission Rates in Lupus Nephritis, with Bahtiyar Toz, MD

Obinutuzumab continued to show efficacy efficacy and kidney-protective potential in people with lupus nephritis (LN) in new real-world data, in new data following on the heels of its United States Food and Drug Administration (FDA) approval earlier this month.1,2

These findings were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Bahtiyar Toz, MD, Icahn School of Medicine, Mount Sinai.

Toz and colleagues shared findings from a small retrospective single-center study evaluating the long-term renal outcomes of obinutuzumab in 26 patients with LN treated between 2015 and 2025. Unlike the controlled populations in the pivotal NOBILITY and REGENCY trials, patients in this cohort had more refractory disease, having progressed past prior therapies such as rituximab, belimumab, mycophenolate mofetil, or voclosporin, and began obinutuzumab with lower baseline kidney function (mean eGFR ~70 mL/min/1.73 m²).2

In this difficult-to-treat group, 40% (n = 10) of patients achieved complete remission (CR) 32% (n = 8) achieved partial remission (PR), and 28% (n = 7) did not have a response (NR) by 24 months, for around a 70% response rate consistent with pivotal trial outcomes. Proteinuria (UPCR) declined significantly over time (P <.001), while eGFR remained largely stable. Among patients achieving CR or PR, 62% maintained stable or improved kidney function over 2 years.1

Of 6 patients who had flares, 2 had CRs and flared 5 years after receipt of obinutuzumab, and had PRs and flared within 1 year. Nine patients in the CR and PR groups were able to discontinue steroids. Among the 7 patients who previously received rituximab, 3 did not respond to obinutuzumab.1

Importantly, some patients who received only 1 obinutuzumab treatment cycle achieved remission, with the earliest responses at 3 months and others emerging up to 18 months later, underscoring that delayed responders may still benefit from ongoing follow-up. Baseline kidney function strongly predicted response: those with higher initial eGFR were significantly more likely to reach CR (P = .014).1

Safety findings were consistent with previous studies. Adverse events occurred in 18 patients, predominantly mild infections and infusion-related reactions within the first 6 months. No new safety signals were observed, even in patients on background immunosuppression.1

HCPLive spoke with Toz to discuss these new data, how obinutuzumab may fit into long-term LN management, and what questions remain in the post-approval era.

Toz emphasized that these findings not only mirror the efficacy seen in phase 3 trials but also demonstrate obinutuzumab feasibility and tolerability in real-world LN care. He shared that he plans to pursue future research exploring biopsy-based markers of tissue recovery and B-cell subset kinetics to better understand obinutuzumab's long-term immunologic effects.

"When you compare (NRs) with the CR and PR group, their eGFR was significantly lower. So basically, we gave obinutuzumab as a last resort. We didn't see a response because they had kidney damage already. So basically, our data was consistent with what the NOBILITY and REGENCY trials showed, [with] CR achieved in about 40% of patients," Toz said.

Toz had no disclosures to report.

References

1. Toz B, Vashistha H, Furie R, et al. Long-Term Effects of Obinutuzumab on Kidney Function in Lupus Nephritis. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #1520

2. Brooks A. FDA Approves Obinutuzumab (Gazyva) for Lupus Nephritis. Article. HCPLive. October 20, 2025. https://www.hcplive.com/view/fda-approves-obinutuzumab-gazyva-for-lupus-nephritis