A Center of Excellence Makes Its Mark on Lupus Research & Clinical Care

Treatment options for patients with systemic lupus erythematosus have surged over the past few decades. Even so, they’re often insufficient to address the full range of symptoms and complications associated with the highly heterogenous disease, requiring continued research to inform the best clinical care.

NYU Langone Health’s Division of Rheumatology, with its world-renowned Lupus Center, has led the way in both regards. “A big focus of the institution is being at the front and center of drug development,” says Amit Saxena, MD, associate professor of medicine. “We’ve been involved in the phase 2 and 3 studies of every drug that’s been approved for lupus in the last 15 years.”

The division’s rheumatologists have likewise been integral to investigating cell therapies, improving safety and quality standards, revising guidelines, and honing research tools. “As a lupus center of excellence, we provide not just standard but state-of-the-art care for the diagnosis and treatment of lupus and lupus-related conditions,” says H. Michael Belmont, MD, professor of medicine. “We’re heavily involved in translational research from the bench to the bedside, and we value funneling those clinical insights back into the lab.”

A particularly potent research tool is NYU Langone’s diverse clinical registry, Specimen and Matched Phenotype Linked Evaluation (SAMPLE), created in 2013. The registry includes well-phenotyped samples from more than 1,300 patients with lupus. “Basic science is incredible and we need it to understand disease mechanisms, but our lupus cohort helps place those findings in a human context,” says Peter M. Izmirly, MD, professor of medicine. “We leverage the registry to help researchers anchor and understand their research findings.”

Leading the Way in Drug Development

As part of its expansive clinical research portfolio, NYU Langone participated in a key phase 3 trial that led to the FDA’s October 2025 approval of the anti-CD20 monoclonal antibody obinutuzumab for treating lupus nephritis (LN). The medical center is also enrolling patients in phase 3 trials of the Janus kinase inhibitor upadacitinib for lupus and the monoclonal antibody anifrolumab for LN.

Dr. Belmont is leading NYU Langone’s participation in a separate phase 1 trial of daratumumab—a monoclonal antibody targeting the CD38 protein on plasma cells—for primary antiphospholipid syndrome (APS). About 30 percent of patients with lupus also have antiphospholipid antibodies, increasing their risk for serious thrombotic events. If successful in primary APS, the therapy could benefit patients with SLE and APS as well.

Innovation in Cell Therapy

NYU Langone is also a major participant in early-phase cellular therapy trials. In a phase 1 trial sponsored by Bristol Myers Squibb, rheumatologists and hematologists are collaborating to administer engineered chimeric antigen receptor (CAR) T cells to patients with severe lupus who have failed at least two prior therapies. Following chemotherapy, participants receive genetically modified CAR T cells designed to deplete remaining autoantibody-producing B cells—an approach Dr. Saxena says could induce a potential immune reset. “Although we don’t yet know how long the benefits of this intervention will last, the patients who have responded are still off all of their lupus medications a few years later,” he says.

In a second cellular therapy trial, sponsored by Nkarta, participants with severe, refractory LN are receiving genetically engineered CAR natural killer (NK) cells from donors. The allogenic NK cells are also designed to target autoantibody-producing B cells but carry less risk of immune system rejection. If successful, the therapy could not only help stave off end-stage kidney disease but also send the disease into remission. “We’re heavily invested in this—this is truly the cutting edge,” Dr. Saxena says.

Vaccine Safety in Lupus

NYU Langone researchers are tackling complex clinical questions beyond drug development. One investigator-initiated trial, based on an idea from Dr. Saxena, is a collaboration with GSK examining the safety and efficacy of the Shingrix shingles vaccine in patients with lupus.

“The concern was that in patients with an immune system that is already ramped up, giving a strong vaccine could cause a flare of their lupus,” he says. In addition to evaluating safety, the trial also offers the chance to explore how lupus medications might suppress the immune response to the vaccine and what interactions occur within the immune system after vaccination.

Studying HCQ Discontinuation

Another investigator-initiated trial, Stopping Hydroxychloroquine In Elderly Lupus Disease (SHIELD), is assessing the drawbacks of indefinite hydroxychloroquine (HCQ) use—the current standard of care. Given the escalating risk of HCQ-associated retinal toxicity with continued use, the multicenter trial aims to answer whether stopping the medication in clinically stable older patients can reduce ocular exposure while avoiding an increased risk of lupus flares.

“Hydroxychloroquine is the cornerstone of lupus therapy, but it’s not without side effects,” Dr. Izmirly says. “The longer patients are on it, the more likely they are to have side effects.”

NYU Langone has been enrolling patients in the randomized, double-blind, placebo-controlled trial, co-led by Dr. Izmirly and Jill P. Buyon, MD, the Sir Deryck and Lady Va Maughan Professor of Rheumatology. “The vast majority of patients I’ve seen don’t want to be on medication for life,” Dr. Izmirly says. “Drug withdrawal studies are becoming more common for a lot of diseases, and we’re hoping to provide clear guidance for lupus as well.”

Re-evaluating Cutoffs for Kidney Biopsy

At the 2025 American College of Rheumatology annual meeting, Drs. Izmirly, Belmont, and Buyon, in collaboration with colleagues at Johns Hopkins University, contributed to data suggesting that for patients with lupus and at least one LN predictor—such as the presence of anti-DNA antibodies or low complement levels—the current urine protein-to-creatinine ratio cutoff of ≥ 0.50 for kidney biopsy might need to be revisited.

The data, gathered as part of the NIH’s Accelerated Medicines Partnership (AMP) collaboration, suggested that ratios between 0.250 and 0.499 also yielded actionable biopsy results. Among patients biopsied after reaching the lower threshold, 69 percent were found to have LN. “As time goes on, we may need to lower the threshold for biopsy based on this collaborative project,” Dr. Izmirly says. “Maybe we’ll catch kidney disease earlier, treat it earlier, and prevent poor outcomes.”

Shaping National Guidelines and Future Research

Drawing on the accumulating data, Dr. Izmirly helped shape the American College of Rheumatology’s latest guidelines for treating SLE, published in November 2025, and is contributing to revised guidelines for LN. In parallel, Dr. Belmont is leading a push for more personalized LN guidelines based on patient-specific characteristics and informed by NYU Langone’s extensive clinical experience.

Looking ahead, a multidisciplinary team is using AI to mine the NYU Langone electronic medical record (EMR) system and learn from the center’s decades of experience. “By leveraging the full breadth of our patient population, we can query our own experience over large numbers of patients with lupus to identify those at risk for flares, severe LN, cardiovascular disease, and more,” Dr. Belmont says. “Those insights can then inform future research and interventions.”