Study: Obinutuzumab Improves Kidney Outcomes in Lupus Nephritis

Adding obinutuzumab, a humanized type II anti-CD20 IgG1 monoclonal antibody, to standard lupus nephritis (LN) therapy improved kidney outcomes and reduced glucocorticoid use in patients with active LN, according to post hoc analyses of the phase 2 NOBILITY trial. Patients with LN receiving obinutuzumab demonstrated a 60% reduction in the risk of unfavorable kidney outcomes, a 57% lower risk of LN flare, and up to 91% decreased likelihood of experiencing significant declines in kidney function compared to those receiving placebo.

LN is a severe complication of systemic lupus erythematosus that can lead to long-term kidney damage. Current standard-of-care treatments effectively manage the disease but often require high doses of glucocorticoids, increasing the risk of adverse effects. This study aimed to determine whether adding obinutuzumab to standard LN therapy could enhance kidney function preservation and reduce glucocorticoid use.

In 2013, the FDA approved obinutuzumab in combination with chlorambucil for treating patients with previously untreated chronic lymphocytic leukemia. In 2017, the FDA approved obinutuzumab for treatment of patients with follicular lymphoma, specifically those who relapsed after or are refractory to, a rituximab-containing regimen or those with previously untreated stage II bulky, III, or IV follicular lymphoma.

The randomized, double-blind trial included patients with active LN (N = 125) who were treated with obinutuzumab (n = 63) or placebo (n = 62) in addition to mycophenolate mofetil and glucocorticoids. The researchers assessed composite kidney outcomes, LN flares, estimated glomerular filtration rate (eGFR) declines, chronic eGFR slope, and the number of patients achieving complete renal response (CRR) on 7.5 mg or less per day of prednisone over a 104-week period.

Patients treated with obinutuzumab experienced slower annual declines in eGFR, with an advantage of 4.1 mL/min/1.73 m²/year (95% CI, 0.14–8.08) over the placebo group. Reductions in eGFR decline of 30% and 40% were 80% and 91%, respectively, in the obinutuzumab cohort. Of patients on Obinutuzumab, 38% also achieved CRR at week 76 with a daily prednisone dose of 7.5 mg or less, compared to 16% in the placebo group (P < .01). However, this difference was reduced by week 104 (38% vs 22%; P = .06).

Limitations of the study include its post hoc design and small sample size.

“Post hoc analyses of NOBILITY demonstrated that compared with standard-of-care therapy, obinutuzumab treatment resulted in superior preservation of kidney function and prevention of LN flares,” the researchers concluded.

Reference

Rovin BH, Furie RA, Terres JAR, et al. Kidney outcomes and preservation of kidney function with obinutuzumab in patients with lupus nephritis. Arthritis Rheumatol. 2024;76(2):247-254. doi:10.1002/art.42734