ACR CONVERGENCE 2021—Patients with systemic lupus erythematosus (SLE) don’t have many approved drugs for treatment. In fact, only three lupus-specific drugs have been produced in the past few decades, with two of them approved in the past year.
“You’ll agree we are not doing well when we compare [treatment options for lupus] to rheumatoid arthritis or many of the other diseases we encounter in the clinic,” said Virginia Pascual, MD, director of the Drukier Institute for Children’s Health and the Ronay Menschel professor of pediatrics at Weill Cornell Medicine Gale and Ira Drukier Institute for Children’s Health, New York City.
Still, researchers continue to explore additional options for lupus patients, including the possibility of precision medicine. Dr. Pascual addressed potential precision targets during the Precision Medicine in Lupus session at this year’s ACR Convergence.
The State of Lupus Treatments
Rheumatologists continue to rely on the small number of therapies available for lupus, as well as glucocorticoids for first-line treatment, even knowing the tremendous side effects the latter therapy can cause, Dr. Pascual said. Many clinical trials related to lupus have failed, including various approaches targeting B cells, co-stimulatory molecules and the interferon pathway, all of which are known contributors to the pathogenesis of disease.
One challenge of precision medicine within lupus is the heterogeneity of the disease. When asked if a single therapy can be developed for such a highly heterogenous disease, Dr. Pascual said she didn’t think so. “Maybe in the future we’ll come to a generalized metabolic alteration that will be targeted by one approach, but this remains to be seen,” she said. “These are different ways to get a lupus phenotype, and we should better understand where each of our patients came from. Either we stratify properly, or it will be difficult to treat everyone the same way.”
Genetics is providing clues for clinicians to better comprehend the complexity of lupus, Dr. Pascual said. “Genetic studies are teaching us that not all mutations leading to lupus result in the same sub-phenotype,” she said. Still, most patients don’t have familial lupus, and every effort should be made to characterize their immune profiles to enable personalized treatments.
2 Studies Shed Light
Dr. Pascual presented the results from several studies that drilled down on the heterogeneity of lupus to better identify treatment targets. One study she shared, from Nehar-Belaid et al., was published in 2020 and focused on profiling approximately 276,000 peripheral blood mononuclear cells (PBMCs) from 33 children with SLE and 11 matched controls.1 Those with SLE had an increased expression of interferon-stimulated genes derived from a group of transcriptionally defined subpopulations that are part of major cell types. These included monocytes, conventional dendritic cells, plasmacytoid dendritic cells, B cells and others. Study researchers then profiled roughly 82,000 PBMCs from adult patients with SLE and found the expansion of these same subpopulations in those with the highest disease activity.