Chromosomal Loop Signatures Could Identify Poor Drug Response in Arthritis

Source: University of Glasgow

Summary: Researchers have discovered that chromosomal loop signatures found in blood samples obtained in early rheumatoid arthritis could identify patients that will not respond adequately to ‘anchor’ treatment drug methotrexate.

Methotrexate (MTX)  is the anchor drug for the treatment of people with new-onset rheumatoid arthritis. However, a significant proportion of patients treated with MTX do not respond to therapy. It can take at least six months to determine if a patient will not exhibit a sufficient response to MTX; this would then lead to a change in treatment. Researchers from the University of Glasgow have investigated whether differences in genomic architecture, as defined by a chromosome conformation signature (CCS) in blood taken pre-treatment from people with early rheumatoid arthritis, could assist in identifying the likelihood of a response to the first line disease-modifying anti-rheumatic drug (DMARD) methotrexate (MTX). The study successfully showed that a CCS found in the blood samples obtained in pre-treatment early rheumatoid arthritis could identify patients that will not respond adequately to MTX with a high degree of accuracy. The study findings were published in the Journal of Translational Medicine.

Autoimmune Disorder

Credit: University of Glasgow

Providing patients with the correct therapy during the early stages of rheumatoid arthritis is essential for preventing long-term disability. It is generally believed that substantial damage can occur as a result of inflammation during the early stages of rheumatoid arthritis, and damage correlates very well with future disability and loss of function. Thus, choosing the correct therapy early in the disease is very important. The study using EpiSwitch to predict who will or will not respond to a given therapy in rheumatoid arthritis. This ability to determine whether or not a patient will respond to their chosen medicine may have far-reaching socio-economic implications, which would not be restricted to just healthcare costs.

Dr. Claudio Carini said, “Despite advances in medicine, not all patients respond favorably to drugs. A proportion of patients under therapy don’t benefit from their treatment, or experience adverse reactions to the medication. The identification of a predictive signature in rheumatoid arthritis creates unique opportunities in the management of the disease.”

More Information: Claudio Carini et al, “Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis”, Journal of Translational Medicine (2018). DOI: 10.1186/s12967-018-1387-9

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