Brad Rovin, MD

Credit: Ohio State University

The use of obinutuzumab may lead to reductions in corticosteroid use and complications of lupus which concern patients’ kidneys, according to new findings presented at the American College of Rheumatology 2023 Convergence in San Diego, California.¹

Specifically, the B cell-depleting drug obinutuzumab, as it is combined with standard therapies, was shown to have reduced kidney-related complications and use of corticosteroids in those with lupus nephritis. Lupus nephritis is a dangerous complication resulting from systemic lupus erythematosus (SLE, lupus) and it is the most common cause of damage to kidneys among those with lupus.

The investigators noted that lupus nephritis is a leading cause of kidney damage particularly among Asian, Black, and Hispanic women in the US who often report more aggressive disease activity and even worse health outcomes.²

The new findings presented at ACR 2023 resulted from an analysis that was done post-hoc regarding the phase 2 results of the NOBILITY trial. The study’s investigators explained that current therapies frequently fall short of preserving kidney function while continuing to minimize side effects of medication, leading to researchers looking for more effective and safer options.

Obinutuzumab is a drug approved for treatment of blood cancers. The drug is also known to target B cells, which maintain a major role in development of lupus and of lupus nephritis.

The randomized NOBILITY study regarding this treatment had been carried out across the US, Latin America, Israel, and the Caribbean. The investigators of that study looked into the efficacy of obinutuzumab in combination with standard therapies and they were compared to standard medications alone.

The study had shown that individuals with cases of proliferative lupus nephritis treated with obinutuzumab with standard-of-care therapy ended up having clinically meaningful improvements. They also were shown to have had in complete and overall renal responses (CRR and ORR) at Weeks 52, 76 and 104 compared with those receiving placebo and standard-of-care therapy.¹

The new post-hoc analysis was led by Brad Rovin, MD, professor of internal medicine and nephrologist for Ohio State University’s Wexner Medical Center, and his team.

Rovin and colleagues found that subjects who had been treated with obinutuzumab reported major improvements and a steroid-sparing effect, reducing the study participants’ risk of kidney-related complications beginning at the 76-week mark of the study.

The research team looked at the results of various elements on kidney-related events in individuals with lupus nephritis, using statistical methods like Cox regression analysis to assess the time until the first kidney-related event. The events they looked at included doubling of serum creatinine, treatment failure, mortality, lupus nephritis flares, and a decline of 30% and 40% in the estimated glomerular filtration rate (eGFR) from the point of baseline.

The team also looked at the effect of a low steroid dose in the achievement of complete renal response at certain weeks without exceeding a higher dose during certain periods. They also looked at racial and national differences.¹

While adverse events were shown to be comparable between the obinutuzumab regimen and standard treatments, the investigators’ post-hoc analysis of the phase 2 study acknowledged the importance of confirmation through larger prospective studies.

“Our post-hoc analysis of belimumab showed that it reduced lupus nephritis flares and was associated with better preservation of kidney function than standard-of-care medication,” Rovin said in a statement.2

Rovin added that this then led him to wonder whether B cells in lupus could have some additional and even some direct detrimental impacts on function of the kidneys.

“When we looked at the NOBILITY data, I was excited to see that obinutuzumab also appears to preserve kidney function better than standard-of-care therapy and also decreases lupus nephritis flares,” Rovin noted. “Now there’s data from two very different B cell-targeted drugs suggesting that reduction of B cells or attenuation of B cell activity may help preserve kidney function in autoimmune disease.”

References

1. ^{Rovin B, Ross Terres J, Giang S, Schindler T, Turchetta A, Garg J, Furie R, Pendergraft III W, Malvar A. Kidney-Related Outcomes and Steroid-Sparing Effects in Patients with Active Lupus Nephritis Treated with Obinutuzumab: A Post Hoc Analysis of a Phase 2 Trial [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/kidney-related-outcomes-and-steroid-sparing-effects-in-patients-with-active-lupus-nephritis-treated-with-obinutuzumab-a-post-hoc-analysis-of-a-phase-2-trial/. Accessed November 12, 2023.}
2. ^{New Analysis Shows Obinutuzumab Reduces Kidney Complications and Steroid Use in Lupus Nephritis Patients. American College of Rheumatology. November 7, 2023. Date accessed: November 12, 2023. https://rheumatology.org/press-releases/new-analysis-shows-obinutuzumab-reduces-kidney-complications-and-steroid-use-in-lupus-nephritis-patients.}