This year has seen significant developments in the treatment of ankylosing spondylitis (AS) and other spondyloarthritis conditions. But how groundbreaking are these new studies? In this article, we delve into some of the most talked-about research results and explore the implications for patients.
A study published in Nature captured significant attention this year by shedding light on a previously misunderstood genetic mechanism that may drive various inflammatory diseases, including spondyloarthritis. Researchers focused on a gene called ETS2, which plays a critical role in regulating inflammation within immune cells known as macrophages. This gene, located in what was once considered a “gene desert” (a region of DNA previously thought to lack any active genetic function), turned out to be integral to controlling inflammatory responses.
The researchers identified a regulatory element within this gene desert that boosts ETS2 activity in macrophages. Excessive activation of this gene was linked to increased inflammation—a hallmark of autoimmune disorders such as inflammatory bowel disease (IBD) and spondyloarthritis. By inhibiting ETS2 activity in laboratory settings, scientists were able to reduce inflammation, pinpointing a potential new therapeutic target for treating these conditions.
Although there are currently no drugs that specifically target ETS2, the study highlighted the potential of MEK inhibitors—medications already used in non-inflammatory diseases—to regulate this gene’s inflammatory impact. However, the use of MEK inhibitors is not without challenges; they come with significant side effects that affect other organs, necessitating the development of more targeted versions. In addition, the MEK inhibitors study has only been completed in lab conditions, not with human subjects. Though this research could pave the way for new therapeutic avenues—not just for spondyloarthritis but for a broader range of inflammatory conditions—it will likely be several years before MEK inhibitors become available for treating spondyloarthritis.1
In another frequently discussed case, a male patient from Russia diagnosed with ankylosing spondylitis in his early 20s found little relief from conventional treatments such as anti-TNF therapies. In 2009, after a stem cell transplant resulted in temporary remission, his condition worsened, leading him to try experimental treatments targeting a specific subset of T cells (TRBV9+T cells) in 2019. This treatment was based on an earlier study from several groups in the United States (including a group led by Dr. Michael Paley, SAA’s Jane Bruckel Early Career Investigator Award-winner) and a group in Russia who described the expansion of these special T cells in AS.
Researchers in Russia claim that this therapy, which focuses on a precise group of immune cells implicated in AS, has led to remarkable improvements in the patient’s symptoms, including reduced pain and increased mobility. His disease has reportedly remained in remission for over four years without the need for traditional immunosuppressive treatments. The Pirogov National Medical Research University, the Institute of Biorganic Chemistry, and the Russian pharmaceutical company BIOCAD collaborated to create Seniprutug, a medication based on this treatment therapy. BIOCAD claims the targeted nature of this approach—focusing solely on the immune cells responsible for inflammation—offers not just a treatment, but a cure.
Is Seniprutug as promising as BIOCAD asserts? As of October 2024, Seniprutug has only been approved by the Russian Ministry of Health. Early limited evidence suggests the drug is safe; however, no concrete evidence is yet available on its success rate in “curing” AS or its impact on large patient populations outside clinical trials. American researchers have not yet indicated a timeline or strong interest in bringing it to the U.S. market. Approval in the U.S., Europe, and other regions with strict regulations would typically require extensive further studies and clinical trials.2
One of the most exciting developments in the treatment of severe autoimmune diseases involves CD19 CAR T-cell therapy, a technique already established in oncology for treating certain cancers. A recent study examined the application of this therapy to patients with severe systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis—three autoimmune diseases that typically require long-term immune suppression.
In this study, 15 patients underwent a single infusion of CD19 CAR T cells following preconditioning with chemotherapy agents fludarabine and cyclophosphamide to reduce the existing immune response. The aim was to essentially “reset” the immune system by depleting B cells, a major contributor to autoimmune activity, in order to induce remission without the need for ongoing immunosuppressive drugs.
All patients with SLE achieved remission based on standard criteria, while patients with myositis and systemic sclerosis showed significant clinical improvements and reductions in disease activity. Notably, none of the patients required further immunosuppressive therapy post-treatment. Although some mild side effects occurred, such as cytokine release syndrome (a common complication of CAR T-cell therapy), the overall safety profile was deemed acceptable for this small patient group.
However, some caution is raised by rare reports of T cell lymphoma in individuals treated with CAR T therapy for cancer. This study not only demonstrated the feasibility of CAR T-cell therapy for autoimmune diseases but also underscored its potential as a long-term solution for conditions that are otherwise difficult to manage. While the current research did not include spondyloarthritis, the success of the therapy in treating other autoimmune conditions raises the possibility that it could be applied to AS and related diseases in the future.3
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