According to a new study from the Queen Mary University of London, diagnosing the profile of diseased joint cells may significantly impact whether specific therapies will effectively treat rheumatoid arthritis (RA) patients. The study was published in Nature Medicine on May 19, 2022. Researchers also discovered several genes associated with resistance to many modern therapies, commonly known as refractory disease, which may provide the key to finding new, effective drugs to help these patients.
Although there have been significant advances in the treatment of arthritis in recent decades, the vast majority of people (about 40 percent) do not respond to specific drug treatments, and 5-20% of people with the disease are resistant to all available medications.
The researchers conducted a biopsy-based clinical study with 164 arthritis patients, testing their response to rituximab or tocilizumab – two drugs used to treat RA. The findings of the actual study, published in the Lancet in 2021, showed that in people with low synovial B-cell signature, only 12% responded to B-targeted therapy (rituximab), while 50% responded to another drug. Tocilizumab). Both drugs were equally effective when patients had a high rate of this genetic signature.
As part of the first study of its kind, sponsored by the Efficacy and Mechanism Evaluation Program (EME), MRC, and NIHR partnerships, the Queen Mary team also looked at cases where patients did not respond to any drug treatment and found that there were 1,277 genes, which were significantly different from them.
To build on this, researchers have used a data analysis method called machine learning models to develop computer algorithms that can predict drug responses in each patient. Machine learning algorithms, including genetic profiles from biopsies, have been very effective in predicting which treatments would work best compared to a model that has only used tissue disease or clinical features.
Research strongly supports the genetic profile of biopsies from arthritic joints before prescribing expensive drugs called biologic target therapy. This can save the NHS and the community a lot of time and money and help avoid potential side effects, joint injuries, and more severe side effects that are common among patients. As well as contributing to the development of therapeutic drugs, such experiments may enlighten people who may not respond to any current medications on the market, underscoring the need for alternative therapies.