New research from Queen Mary University of London, published in nature medicine, have shown that the molecular profiling of diseased joint tissue can significantly influence whether specific drug therapies will work to treat rheumatoid arthritis (RA) patients. The researchers also identified specific genes associated with resistance to most available drug treatments, commonly referred to as refractory diseases, that may provide the key to developing new, successful drugs to help these people.
While much progress has been made over the past decades in the treatment of arthritis, a significant number of patients (about 40%) do not respond to specific drug therapies, and 5–20% of people with the disease are resistant to all existing forms. Medicine.
Researchers conducted a biopsy-based clinical trial involving 164 arthritis patients to test their responses to rituximab or tocilizumab — two drugs commonly used to treat RA. Original test results published in the Lancet demonstrated in 2021 that only 12% of patients with a reduced synovial B-cell molecular signature responded to a drug that targets B cells (rituximab), while 50% responded to an alternative drug (tocilizumab). When patients had high levels of this genetic signature, both drugs were equally effective.
As part of the first study of its kind, funded by the Efficacy and Mechanisms Evaluation (EME) Program, an MRC and NIHR partnership, the Queen Mary team also looked at cases where patients did not respond to treatment through any . drugs and found that there were 1,277 genes that were specifically unique to them.
Building on this, the researchers applied a data analysis technique called machine learning models to develop computer algorithms that can predict drug response in individual patients. Machine learning algorithms, which included gene profiling from biopsies, performed significantly better at predicting which treatment would work best than a model that used only tissue pathology or clinical factors.
The study strongly supports the case for performing gene profiling of biopsies from arthritic joints before prescribing expensive so-called biological targeted therapies. This can save the NHS and society a considerable amount of time and money and helps avoid potentially unwanted side effects, joint damage, and worse outcomes that are common in patients. As well as influencing treatment prescription, such trials may also shed light on which people may not respond to any existing drugs on the market, emphasizing the need to develop alternative drugs.
Professor Kostantino Pitzalis, Professor of Rheumatology at Queen Mary University of London, said: “Incorporating molecular information before prescribing arthritis treatment to patients could forever change the way we treat this condition. A personalized approach to patients that has far greater chances of success rather than trial-and-error drug prescription, which is currently the norm.
“These results are incredibly exciting in demonstrating the potential at our fingertips, however, the field is still in its infancy and additional confirmatory studies will be needed to fully realize the promise of precision medicine in RA.
“The results are also important in finding solutions for people who unfortunately don’t have the treatment that currently helps them. Knowing which specific molecular profiles influence this, and which pathways affect disease activity in these patients.” Continuing to develop new drugs that can help bring better results and much-needed relief from aches and pains.”
The inclusion of these signatures in future clinical trials will be an essential step in translating these findings into routine clinical care.
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