Potential of precision medicine in rheumatology grows

Precision medicine is poised to transform the treatment of rheumatic disease. Rheumatologic patients and clinicians can look to the kinds of changes that have dramatically altered the face of cancer diagnosis, treatment, and survival in recent years, and for the same reasons. Conventional approaches to treatment rely on disease phenotypes and their clinical presentation. Genomic, proteomic, and other omic technologies are revealing disease subtypes and precise molecular targets that allow for more targeted and effective treatment approaches.

“In cancer, the newer treatments being approved are no longer just based on the organ where the cancer originated, but based on the mutation or the genetic instability that triggers and promotes the disease,” said Andrea Fava, MD, Assistant Professor of Rheumatology, Johns Hopkins School of Medicine. “You find the mechanism, no matter what clinical disease is showing, and treat the mechanism. We can find something along those same lines in rheumatic diseases.”

Dr. Fava will discuss the latest urine proteomic findings in lupus nephritis during Precision Medicine in Rheumatic Diseases on Saturday, November 12, from 11 a.m.–12 p.m.  ET in Terrace Ballroom I. Meeting participants have the option to attend the session in person or on the meeting website via livestream, or to view the session on demand.

Dana Orange, MD, MS, Assistant Professor of Rheumatology, Rockefeller University, will explore the growing role of transcriptomics in understanding the mechanisms underlying symptoms of rheumatoid arthritis such as pain, morning stiffness, and flares.

Lupus is a particularly useful model for precision medicine in autoimmune disease, Dr. Fava said. More than 100 different polymorphisms—distinct genetic mutations—have been identified in lupus. And while multiple polymorphisms converge into similar clinical pictures, each mutation can generate its own mechanism of disease.

“Everybody who presents with similar disease features can have a different mechanism driving those features,” he explained. “That is one reason our current treatments, based on clinical features, do not work for everybody. If we can identify the molecular mechanisms that are active and treat that mechanism, we can be much more precise and effective, whatever the disease looks like in clinic.”

The diagnosis and management of lupus nephritis is highly proteinuria centric, Dr. Fava continued. Many patients are asymptomatic and diagnosed only on kidney biopsy prompted by proteinuria. Proteinuria changes are also used as markers of treatment efficacy in clinical trials and in practice.

“Proteinuria is an accepted biomarker, but it is not always elevated when patients have inflammation in the kidney,” Dr. Fava said. “If you have been treated for more than three years and have complete resolution of proteinuria and take another kidney biopsy, there is a 40 percent chance the patient still has inflammation in the kidney.”

Immunosuppression is the usual clinical intervention, but some patients experience disease flare on treatment.

“The most immediate application of precision medicine would be a reliable way to assess inflammation in the kidney without having to perform a biopsy every few years,” Dr. Fava added. “The goal is a liquid biopsy based on urine samples, a noninvasive biomarker that reflects tissue biology grounded in mechanism. That would allow us to tailor treatment to each patient’s need. We’re applying this omics approach to lupus nephritis right now, and it can be extended to other inflammatory diseases.”