Arthritis Oral Medication

Methotrexate is considered the first-line treatment for rheumatoid arthritis (RA), as it has a long record of safety and efficacy. But that doesn’t mean methotrexate works for everyone.

In fact, a 2018 study found that 43 percent of RA patients were non-responders to this drug. The authors found that such factors as being negative for rheumatoid factor (an autoantibody that plays a role in rheumatoid arthritis), having a higher tender joint count, and higher anxiety scores played a role in people who didn’t respond to methotrexate. Other research has suggested that being a smoker or having higher disease activity when starting methotrexate might explain why some people don’t respond to it.

Now a new study has found that specific epigenetic changes — modifications to genes that switch them on and off — are associated with good or poor response to methotrexate.

Every cell in your body contains the same DNA, yet cells function very differently thanks to a process called methylation. During methylation small compounds (methyl groups) attach to DNA molecules, which changes how they’re expressed. These changes occur naturally as you develop, but they can also happen as a result of influences in the environment.

In recent years, scientists have been studying about how differences in methylation patterns might increase or decrease the chances of developing diseases, including RA. According to this new study, published in the journal Arthritis Research & Therapy, methylation patterns might also impact RA patients’ methotrexate response.

To conduct the study, researchers took blood samples from 294 RA patients in the Netherlands who had not yet tried methotrexate and had the DNA and methylation patterns of their white blood cells analyzed. They found that those who had lower levels of methylation at the beginning of the study were more apt to respond well to methotrexate (as measured after three months of treatment with the drug).

“This is in line with our hypothesis that higher baseline global DNA methylation levels are more difficult to inhibit and that this is associated with non-response,” the authors wrote.

Whether methylation patterns can used to predict who should take methotrexate instead of relying on trial-and-error still remains to be seen, though it seems possible.

For now, “the underlying pathway, as well as the potential added value [of using methylation] in a prediction model for [methotrexate] response requires further exploration,” the authors wrote.

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