Abstract: TH-OR30
Kidney-Related Outcomes in Patients with Active Lupus Nephritis Treated with Obinutuzumab: A Post Hoc Analysis of the Phase 2 NOBILITY Trial
Session Information
- Glomerular Diseases: Clinical and Translational Studies
November 02, 2023 | Location: Room 103, Pennsylvania Convention Center
Abstract Time: 05:51 PM - 06:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Rovin, Brad H., Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, United States
- Alfonso Ross Terres, Jorge, Genentech Inc, South San Francisco, California, United States
- Giang, Sophia, Genentech Inc, South San Francisco, California, United States
- Schindler, Thomas, F. Hoffman-La Roche Ltd, Basel, Switzerland
- Turchetta, Armando, F. Hoffman-La Roche Ltd, Basel, Switzerland
- Garg, Jay P., Genentech Inc, South San Francisco, California, United States
- Furie, Richard, Northwell Health, Great Neck, New York, United States
- Pendergraft, William Franklin, Genentech Inc, South San Francisco, California, United States
- Malvar, Ana, Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina
Background
Preservation of long-term kidney function is a major therapeutic goal in lupus nephritis (LN). In the randomized, double-blind, placebo-controlled, Phase 2 NOBILITY trial (NCT02550652; PMID: 34615636), patients with proliferative LN receiving obinutuzumab with standard-of-care therapy showed clinically meaningful improvement in complete and overall renal responses at Weeks 52, 76 and 104 compared with those receiving placebo and standard-of-care therapy. We conducted a post hoc analysis of NOBILITY to assess kidney-related outcomes.
Methods
Cox regression analysis was conducted for the time to first kidney-related event (death, doubling of serum creatinine or treatment failure), LN flare and first 30% and 40% eGFR decline from baseline. The eGFR slope was assessed in a linear mixed-effects model.
Results
Obinutuzumab significantly reduced the risk of kidney-related events or death (HR, 0.40; 95% CI, 0.20 to 0.80), LN flare (HR, 0.43; 95% CI, 0.20 to 0.95) and first eGFR decline of 30% (HR, 0.20; 95% CI, 0.06 to 0.61) and 40% (HR, 0.09; 95% CI, 0.01 to 0.73) (Figure). Risk of sustained eGFR decline of 30% and 40% was numerically lower, and a significant difference in attenuation of eGFR slope decline was observed between patients receiving obinutuzumab and standard-of-care therapy and those receiving placebo and standard-of-care therapy (annual slope difference, 4.10 mL/min/year; 95% CI, 0.14 to 8.08).
Conclusion
Obinutuzumab, in addition to increasing the possibility of achieving a complete renal response, significantly reduced the risk of kidney-related events, eGFR decline, time to LN flare and eGFR slope decline in a post hoc analysis, suggesting that obinutuzumab in combination with standard-of-care therapy may positively impact kidney-related outcomes. Obinutuzumab is being evaluated in patients with active proliferative LN in the global registrational Phase 3 REGENCY trial (NCT04221477).
Funding
- Commercial Support – This study was funded by Genentech, Inc., a member of the Roche Group. Editorial assistance was provided by Health Interactions, Inc., and funded by F. Hoffmann-La Roche Ltd.