POS0321 KIDNEY-RELATED OUTCOMES WITH OBINUTUZUMAB IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS: A PRE-SPECIFIED EXPLORATORY ANALYSIS OF THE REGENCY STUDY

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Background: Lupus nephritis (LN) is the most common, severe organ-threatening manifestation of systemic lupus erythematosus. The randomised, double-blind, placebo-controlled, Phase III REGENCY study (NCT04221477) demonstrated superiority of obinutuzumab over placebo in achieving complete renal response at Week 76 when added to standard therapy (mycophenolate mofetil plus glucocorticoids) in patients with active LN. Objectives: To assess the effects of obinutuzumab on time to LN flare, time to an unfavourable kidney outcome and annualised estimated glomerular filtration rate (eGFR) slope during the REGENCY study. Methods: In this pre-specified analysis of REGENCY, time to LN flare was assessed between Weeks 24 and 76 by Cox regression. The composite outcome of death, doubling of serum creatinine or treatment failure was defined as an unfavourable kidney outcome. Time to an unfavourable kidney outcome from baseline to Week 76 was also assessed by Cox regression after stratifying for race and region. Finally, linear mixed-effects modelling was used to assess eGFR slope between Weeks 12 and 76. These analyses were not controlled for type I error. Results: Between Weeks 24 and 76, the proportion of patients with LN flare was lower in the obinutuzumab arm (11.1%) than in the placebo arm (23.5%), with a hazard ratio of 0.44 (95% CI, 0.24 to 0.82; P =0.0074) (Figure 1A). The proportion of patients with unfavourable kidney outcomes in the obinutuzumab arm (8.10%) was also lower than in the placebo arm (21.30%), with a hazard ratio of 0.37 (95% CI, 0.18 to 0.75; P =0.0039) (Figure 1B). Numerical attenuation of eGFR decline from Week 12 to Week 76 was observed in the obinutuzumab arm with the annualised eGFR slope calculated as −0.71 (SE=1.454) compared with −4.39 (SE=1.454) in the placebo arm, with a difference in eGFR slope of 3.68 (SE=2.055; P =0.0732), favouring patients treated with obinutuzumab (Table 1). Conclusion: This pre-specified exploratory analysis of the REGENCY study demonstrated that obinutuzumab significantly reduced the occurrence of LN flares and unfavourable kidney outcomes and attenuated the annualised decline in kidney function compared with placebo-treated patients. Together with the significantly higher proportion of patients achieving a complete renal response in the obinutuzumab arm, these findings suggest that obinutuzumab affords long-term kidney survival benefits compared with standard therapy. REFERENCES: NIL . Acknowledgements: Funded by F. Hoffmann-La Roche Ltd. Editorial assistance was provided by Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd. Disclosure of Interests: Brad H. Rovin consulting fees from F. Hoffmann-La Roche Ltd/Genentech, Inc., William F. Pendergraft III shareholder of F. Hoffmann-La Roche Ltd, employee of Genentech, Inc., Liz Lightstone consulting fees from Alexion, AstraZeneca, F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Kezar, Novartis, Otsuka and Pfizer, Eric Daugas lecture fees from GlaxoSmithKline and AstraZeneca, consulting fees from Amgen, AstraZeneca, GlaxoSmithKline, Novartis and Otsuka, support for attending meetings and travel from Alexion, AstraZeneca, CSL, GlaxoSmithKline, Otsuka, and Vifor, Richard A. Furie consulting fees from Genentech, Inc. and GlaxoSmithKline, research support from Genentech, Inc. and GlaxoSmithKline, Theodore A. Omachi shareholder of F. Hoffmann-La Roche Ltd, employee of Genentech, Inc., Imran Hassan employee of F. Hoffmann-La Roche Ltd, Elsa Martins employee of F. Hoffmann-La Roche Ltd, Thomas Schindler shareholder of F. Hoffmann-La Roche Ltd, employee of F. Hoffmann-La Roche Ltd, Jay P. Garg shareholder of F. Hoffmann-La Roche Ltd, employee of Genentech, Inc., Luis Fernando Quintana Porras consulting fees from Genentech, Inc., GlaxoSmithKline and Otsuka, Piotr Leszczyński: None declared. Ana Malvar consulting fees from Genentech, Inc. and F. Hoffmann-La Roche Ltd. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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