As the 21st century unfolds, rheumatologists will most likely transition from prescribing lupus patients broad immunosuppressants to more targeted treatment approaches. The first of these targeted therapies, belimumab, heralds a new era of lupus treatments. Research into the cross-talk between different immune pathways in systemic lupus erythematosus (SLE) should yield more treatments that will transform patients’ lives.
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“To hope that any one target is going to have a profound effect on disease is not right,” says Mary “Peggy” Crow, MD, chief of the Division of Rheumatology at the Hospital for Special Surgery and New York-Presbyterian/Weill Cornell Medical Center, New York. Dr. Crow is also co-chair of the Scientific Advisory Board of the Lupus Research Alliance. She believes the future lies in combination therapies. “I think we probably need to target several pathways,” she says, noting the growing understanding of the roles of the innate immune system, T cells and B cells in lupus pathophysiology.
Identification of New Therapies
A new and innovative partnership will likely take the lead in revealing these new pathways. The National Institutes of Health (NIH), pharmaceutical companies and nonprofit organizations, including the Lupus Research Alliance, joined forces to form the Accelerating Medicines Partnership (AMP). The AMP’s focus is to ascertain and define biological pathways that may be used to identify relevant drug targets.1 One goal is to address nephritis in SLE. The plan relies on RNA sequencing of patient kidney biopsies to “pull lupus into the 21st century,” says Michelle Petri, MD, MPH, co-director of the Hopkins Lupus Center, Johns Hopkins Medicine, Baltimore. “This is what the future will be,” she adds.
Peter Lipsky, MD, former director of the intramural research program and the autoimmunity branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the NIH, leads the second dominant approach, which will likely identify new drugs for lupus. He co-founded AMPEL BioSolutions in Charlottesville, Va. Commissioned by the Lupus Research Alliance’s legacy organizations, in 2013, he began developing a multi-pronged computer analysis approach to rank existing drugs in the marketplace to be repositioned for the safe, effective treatment of lupus. The analysis identified ustekinumab, a monoclonal antibody targeting interleukin (IL) 12 and IL-23 that is approved for treating psoriasis and Crohn’s disease.2 Dr. Lipsky and colleagues proposed the treatment may also be effective in targeting T cells in SLE.
The Lupus Research Alliance brought this information to the pharmaceutical company Janssen and persuaded it to perform a phase 2 trial of ustekinumab for lupus. Last year, the investigators published positive results, raising hopes that lupus patients may soon have a new treatment option.3