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Genes can predict response to arthritis treatment

Friday May 20th 2022

Molecular profiling can help to predict the effectiveness of specific drug treatments on rheumatoid arthritis, British researchers have reported.

Findings of an "incredibly exciting" new study by a team at Queen Mary University of London, published in *Nature Medicine*, also found specific genes associated with refractory disease, which could open the door to the development of new drugs to help those affected.

Researchers say this breakthrough could significantly change the way that RA patients are treated.

About 40% of arthritis patients do not respond to specific drug therapies, and 5-20% of people with the disease are resistant to all current forms of medication.

For this the first-of-its-kind study, researchers carried out a biopsy-based clinical trial with 164 RA patients, to test their responses to either rituximab or tocilizumab, which are two drugs commonly used to treat the condition.

The results of the original trial were published in *The Lancet* in 2021, which found in those patients with a low synovial B-cell molecular signature only 12% responded to a medication that targets B cells (rituximab), while 50% responded to tocilizumab. When patients had high levels of this genetic signature, the two drugs were similarly effective.

The team also looked at the cases where patients did not respond to any of the drugs treatment and found 1,277 genes that were specifically unique to them.

They went on to apply machine learning models to develop computer algorithms, including gene profiling from biopsies, to predict drug response in individual patients. These were better at predicting which treatment would work best compared to a model that used only tissue pathology or clinical factors.

The authors say their findings support the case for gene profiling of biopsies from arthritic joints before prescribing expensive biologic targeted therapies as it would save the NHS time and money and prevent patients suffering unwanted side-effects and joint damage.

Professor Costantino Pitzalis, Versus Arthritis professor of rheumatology at Queen Mary University of London, said: "Incorporating molecular information prior to prescribing arthritis treatments to patients could forever change the way we treat the condition.

"Patients would benefit from a personalised approach that has a far greater chance of success, rather than the trial-and-error drug prescription that 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 required to fully realise the promise of precision medicine in RA."

Rivellese F, Surace A, Lewis MJ et al. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. *Nature Medicine* 19 May 2022; doi: 10.1038/s41591-022-01789-0


Tags: Genetics | Rheumatology | UK News

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