Obinutuzumab attenuates kidney decline in lupus nephritis

Obinutuzumab was shown to reduce the decline in estimated glomerular flow rate (eGFR) in patients with lupus nephritis. It also decreased the incidence of unfavourable kidney outcomes.

Obinutuzumab is a type 2, optimised, anti-CD20 monoclonal antibody that kills B cells effectively. The recently published, double-blind, phase 2 NOBILITY study (NCT02550652) randomised patients with lupus nephritis 1:1 to either 100 mg of obinutuzumab (n=63) or placebo (n=62) [1,2]. Doses were administered at weeks 0 and 2, followed by doses at weeks 24 and 26. Both groups continued with the standard of care, which included a mycophenolate-based lupus regimen. Complete renal response (CRR) was significantly improved in the obinutuzumab group up to 2 years later [1].

Dr Brad Rovin (Ohio State University, OH, USA) and colleagues presented a post hoc analysis of NOBILITY, investigating other kidney outcomes [2]. This included the time to first unfavourable kidney outcome and eGFR slope between week 12 and week 104.

Unfavourable kidney outcomes were reduced in the obinutuzumab group (HR 0.40; 95% CI 0.20–0.80). The adjusted mean difference in eGFR at 2 years was 9.7 mL/min/1.73 m² (95% CI 1.7–18; P=0.017), favouring the obinutuzumab group. Obinutuzumab annual slope difference of eGFR was -0.43 (95% CI -3.16 to 2.31); this was -4.52 (95% CI -7.41 to -1.66) for placebo.

While Dr Rovin noted that these data should be viewed cautiously since they are post hoc and that the work needs to be tested prospectively, he concluded that “these data suggest better long-term preservation of kidney function with obinutuzumab.” The phase 3 REGENCY trial (NCT04221477) will prospectively evaluate obinutuzumab for lupus nephritis, and it has finished recruiting.

1. Furie RA, et al. Ann Rheum Dis. 2022 Jan;81(1):100-107.
2. Rovin B, et al. Kidney-Related Outcomes in Patients with Active Lupus Nephritis Treated with Obinutuzumab: A Post Hoc Analysis of the Phase 2 NOBILITY Trial. TH-OR30, ASN Kidney Week 2023, 2–5 November, Philadelphia, PA, USA.

 

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Posted on 28 November 202328 November 2023