With its large portfolio of National Institutes of Health–sponsored, industry-backed, and investigator-initiated interventional and observational trials targeting systemic lupus erythematosus (SLE), NYU Langone Health has vigorously pursued the disease from its biological beginnings to the final course of treatment. In combination with its rich basic science program, the forward-looking clinical trials unit is committed to bringing highly promising therapeutic interventions to the full spectrum of patients with SLE.
Clinical investigators are now broadening their reach with innovative studies that could open the door to noninvasive diagnostics and new drugs initially developed for other conditions. Amit Saxena, MD, assistant professor of medicine, says NYU Langone’s ambitious efforts include taking part in new investigations of MRI-based methods for diagnosing lupus nephritis and steroid-induced osteoporosis and other trials to determine whether anti-psoriasis medications might benefit patients who have lupus as well.
Identifying Osteoporosis in People with Lupus
The collaborative Bone Quality in Glucocorticoid-Induced Osteoporosis study is testing whether a new, MRI-based protocol developed by Gregory Chang, MD, MBA, associate professor of radiology, might help identify glucocorticoid-induced osteoporosis in patients who have lupus. “We are evaluating the idea that osteoporosis due to glucocorticoid exposure might be different from other types of osteoporosis,” says Dr. Saxena. That finding could suggest that the dual-energy X-ray absorptiometry (DXA) bone density scan, the current standard of care, may not capture differences in the reduced bone mass and microarchitectural deterioration of bone tissue.
The research compares the new MRI protocol to DXA scans to examine potential bone loss in patients who have lupus, with or without glucocorticoid exposure. An early evaluation of the DXA data did not show an association of low bone density with glucocorticoid use, a risk factor. This result suggests that a DXA scan alone may be insufficient to determine whether bone loss has occurred, especially based on traditional definitions of osteoporosis or osteopenia in younger patients.
If the new MRI method proves effective, “this could really change the standard of care,” Dr. Saxena says. “We have a lot of younger patients with lupus who have been exposed to steroids and we don’t necessarily know how to monitor or treat them for their bone loss. This might give us a new direction in how aggressively we should be following them.”
NYU Langone’s industry partnerships are further enriching the clinical trial program by allowing medical researchers to study the origins of SLE and its associated complications, examine the utility of prediction and response biomarkers, and give patients the opportunity to participate in cutting-edge therapeutic approaches.
With support from AMPEL BioSolutions, a multicenter trial now in the enrollment stage will compare kidney biopsies to four separate MRI-based imaging techniques for diagnosing presumed lupus nephritis. The Dynamic Imaging of Variation in Lupus Nephritis (DIVINE) trial will evaluate how well the imaging techniques compare to biopsies in measuring intrarenal blood flow, perfusion, cellularity, fibrosis, and atrophy within the patients’ kidneys.
Beyond their invasive nature, Dr. Saxena says, biopsies can carry significant side effects and yield confounding pathology results. “The study will be comparing the results of those techniques to get a sense if we could noninvasively diagnose patients with lupus nephritis,” he says. “That could be another potential game changer.”
Psoriasis Medications May Have Anti-Lupus Effects
In collaboration with other major industry partners, several trials have taken an innovative tack in developing new drugs. One multicenter Phase II drug trial, sponsored by Bristol-Myers Squibb, is exploring the anti-lupus potential of a highly selective inhibitor of tyrosine kinase 2, or TYK2, given orally.
TYK2 has multiple effects on the body’s immunomodulatory and inflammatory responses, Dr. Saxena says. Although its mediation of immune signaling may be critical to normal immune responses in healthy individuals, accumulating evidence suggests that the protein’s aberrant expression may lead to signaling that promotes autoimmunity. A separate study recently published in the New England Journal of Medicine suggests that the TYK2 inhibitor can effectively treat plaque psoriasis as well. “There is always the question of overlap, particularly in regard to skin disease in lupus and psoriasis and the idea that some medicines might be useful for both,” he says.
Accordingly, another multicenter clinical trial, just beginning enrollment for Phase III after posting successful Phase II results, is testing the anti-lupus effects of ustekinumab (Stelara®), which is already approved for psoriasis and psoriatic arthritis. The randomized, double-blind, placebo-controlled study is aiming to recruit about 500 participants.
Shared Pathology in Lupus and Psoriasis Could Expand Treatment Options
The trials, Dr. Saxena says, could help open up an exciting new avenue of investigation for NYU Langone researchers and their collaborators. “It’s a question of really examining other medicines approved for psoriasis, in light of anecdotal evidence suggesting that some of those might also be helpful in people who have lupus,” he says. Such examinations might reveal whether a shared mechanism of action against similarities in the pathogenesis of lupus and psoriasis rashes could indeed benefit both groups of patients. If so, NYU Langone promises to be at the forefront in further expanding care for patients with SLE.