New Analysis Shows Obinutuzumab Reduces Kidney Complications and Steroid Use in Lupus Nephritis Patients

ATLANTA — A post-hoc analysis of the phase II NOBILITY trial that will be presented at ACR Convergence 2023, the American College of Rheumatology’s (ACR) annual meeting, found the B cell-depleting drug obinutuzumab combined with standard therapies reduced kidney-related complications and corticosteroid use in patients with lupus nephritis (Abstract #0784).

Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE, lupus) and the most common cause of kidney damage in lupus patients. In the U.S., Black, Hispanic, and Asian women are more likely to develop lupus nephritis and to have more aggressive disease activity with worse outcomes. The goal of treatment for all patients is to preserve kidney function while limiting medication side effects. Current therapies do not always achieve these aims, so there is an urgent need for more effective, less toxic options.

One potential option is the B cell-depleting drug, obinutuzumab, which has been approved to treat blood cancers. B cell-targeted medications are of particular interest because abnormal B cells play an important role in the development of lupus and lupus nephritis.

The randomized controlled phase II NOBILITY trial aimed to determine the effectiveness of obinutuzumab plus standard therapies in lupus nephritis patients. It found that patients who received obinutuzumab improved more than those who only received standard medications, usually corticosteroids and immunosuppressants. Serious side effects and complications did not seem to increase with the addition of obinutuzumab. And unlike many trials conducted in a single country, the NOBILITY trial took place in the U.S., Israel, Latin America, and the Caribbean, leading to a mix of patients that more closely reflects the groups affected by lupus and lupus nephritis.

In the post-hoc (after-the-fact) analysis, Brad Rovin, MD, a nephrologist and professor at the Ohio State University Wexner Medical Center, and his clinical trials team, assessed other aspects of the NOBILITY trial, including whether combining obinutuzumab with standard therapies could reduce kidney-related complications and steroid use.

The results showed that the addition of obinutuzumab significantly reduced the risk of all kidney-related complications in lupus nephritis patients. It also had a steroid-sparing effect (meaning lower doses of steroids were needed) starting at 76 weeks in the trial.

Rovin has been involved in several trials looking at various B cell-targeted drugs, including belimumab, the first approved treatment for adult lupus nephritis.

“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 says. “This made me wonder if B cells in lupus may have some additional, perhaps direct detrimental effects on kidney function, besides leading to autoantibody production. 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. 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.”

Rovin says side effects of the obinutuzumab regimen were similar to those of standard treatments, with adverse events occurring in 25% and 30% of patients, respectively. There was one patient death in the obinutuzumab-treated group compared to four deaths among patients receiving standard therapies.

Rovin says the main limitation is that this is a post-hoc study of a completed phase II trial and that the findings will need to be confirmed in a larger prospective study.  

Still, he says, “The [B cell trials] have implications for the long-term management of lupus nephritis, and also raise the question of what B cells may be doing to contribute to the functional deterioration of the kidneys, opening a whole new area of research with potential applications to kidney diseases outside of lupus.”

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Amanda Head
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About ACR Convergence
ACR Convergence, the annual meeting of the American College of Rheumatology, is where rheumatology meets to collaborate, celebrate, congregate, and learn. With more than 320 sessions and thousands of abstracts, it offers a superior combination of basic science, clinical science, business education and interactive discussions to improve patient care. For more information about the meeting, visit the ACR Convergence page, or join the conversation on Twitter by following the official hashtag (#ACR23).

About the American College of Rheumatology
Founded in 1934, the American College of Rheumatology (ACR) is a not-for-profit, professional association committed to advancing the specialty of rheumatology that serves nearly 8,500 physicians, health professionals, and scientists worldwide. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatology professionals are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.