Analyzing the Efficacy, Safety of Obinutuzumab in Lupus Nephritis

A recent study assessed the safety and efficacy of the treatment with obinutuzumab for patients with active lupus nephritis. The findings, published in the New England Journal of Medicine, suggest that obinutuzumab added to standard therapy is efficacious in this patient population. Rheumatologist and lupus expert Dr. Mithu Maheswaranathan spoke to DocWire News about the implications of these promising findings.

DocWire News: What was the primary objective of the study assessing obinutuzumab in active lupus nephritis?

Dr. Mithu Maheswaranathan: Obinutuzumab is a type II anti-CD20 monoclonal antibody, which induces deeper B-cell depletion than other anti-CD20 agents currently available like rituximab. So the study objective for this study was to evaluate the efficacy and safety of obinutuzumab when compared with placebo, added to standard treatment in lupus nephritis—mycophenolate mofetil plus steroids.

Talk to us about the study and its findings.

This study was a phase 3, double-blinded, placebo-controlled trial across 15 countries from 2020 to 2023. They enrolled patients with lupus and biopsy-proven lupus nephritis—so class 3, 4, 5—that had at least 1 gram of proteinuria by UPC [urine protein to creatinine ratio], and they excluded patients with end-stage renal disease or that had an eGFR [estimated glomerular filtration rate] less than 30. The patients were randomized to receive either obinutuzumab infusions or placebo, while continued in both groups on standard therapy, which is the mycophenolate mofetil plus glucocorticoids [such] as prednisone. And ultimately the study found that the patients that received obinutuzumab had a higher renal response rate than the placebo. So 46% versus 33% in the placebo group for their lupus nephritis response. So that was ultimately a positive study showing that obinutuzumab improved the renal response rate in lupus nephritis.

How does the efficacy of obinutuzumab compare to other biologic therapies or standard treatments for lupus nephritis?

This study shows us that obinutuzumab, when added to standard therapy with mycophenolate mofetil and glucocorticoids, results in improved renal response rates for nephritis. However, we don’t have head-to-head studies that compare obinutuzumab to other standard therapies that we’re currently using for lupus nephritis, so we don’t know the efficacy of obinutuzumab compared to other first-line therapies such as belimumab or cyclophosphamide.

What are the potential implications of this study for clinical practice in treating active lupus nephritis?

This study suggests a potential role of obinutuzumab to be added to lupus nephritis treatment in patients who are not responding to standard therapy. One thing that’s important to note is that this study enrolled patients from 2020 to 2023, so before the new 2024 ACR [American College of Rheumatology] guidelines for lupus nephritis management were released. And we know these new guidelines recommend use of triple therapy, whereas this study used dual therapy, which was the standard of care at the time in the 2020 to 2023 window. So again, we don’t know how current triple therapy regimens would compare to obinutuzumab. When thinking about some of the clinical implications with this study, we know that previous work that looked at the use of anti-CD20 agents in lupus nephritis, such as rituximab in the LUNAR trial, those studies did not show efficacy of rituximab for lupus nephritis. So with this new data, it suggests that obinutuzumab would be a more optimal choice over rituximab if a rheumatologist is considering adding a B-cell–depleting agent to a patient that has refractory lupus nephritis that’s not responding to first-line therapy.

What future research is needed to further confirm the long-term efficacy and safety of obinutuzumab in lupus nephritis?

Overall, the adverse events were similar between the obinutuzumab and placebo group, but the study did show [a] higher rate of more serious adverse safety events in the obinutuzumab group compared to placebo, particularly related to COVID-19 infection. It’s important to know the study began enrollment in 2020, and these serious COVID-19 related events occurred very early in the trial. So now with the prevalence of vaccines and antiviral treatments for COVID, there are ways to mitigate the potential risk of this drug, but [we] must consider the infection risk when we are prescribing this medication and other anti-CD20 agents. The 2024 ACR guidelines in lupus nephritis, I think, can be a helpful guide, and they recommend consideration of anti-CD20 therapy in refractory disease. So if the patient doesn’t respond to initial triple therapy, you could consider addition of obinutuzumab.

And finally, I think in terms of future research, we also again need these studies that compare obinutuzumab to the other current first-line agents. And this would be interesting to help us better assess the efficacy of obinutuzumab compared to our new standard of therapy, so current recommendations for triple therapy or other agents besides mycophenolate, which was the only agent that was compared to obinutuzumab in this study. So certainly, further research to go, but this new drug in use in lupus nephritis appears promising.