Research into Methotrexate Could Lead to Improved Treatments for Rheumatoid Arthritis

Dr. Olsen

Doctors know the benefits of methotrexate for patients with rheumatoid arthritis (RA): it limits or reduces joint damage while improving joint function, it’s easy to take (as most patients take the drug by mouth once a week), and it’s fairly inexpensive.

Although the drug has been prescribed for more than 60 years, the manner in which methotrexate helps control the immune system’s attack on joints remains a mystery.

Enter Nancy J. Olsen, MD, professor of medicine and chief of rheumatology at the Penn State Milton S. Hershey Medical Center in Hershey, Pa., who has been working to solve the methotrexate mystery. Thanks in part to a grant from the Rheumatology Research Foundation, Dr. Olsen and her colleagues are studying blood samples from RA patients treated with methotrexate in the hope of discovering how the drug interacts with immune system cells.

Dr. Olsen works closely with Thomas Aune, PhD, professor of medicine and pathology, microbiology, and immunology at the Vanderbilt University Medical Center in Nashville, Tenn., her partner in the research. Dr. Aune’s focus is in the laboratory, looking for patterns in blood samples. Their back-and-forth interactions led to theories about the drug.

“If we can figure out how methotrexate works, maybe we can figure out how to improve treatments,” Dr. Olsen says.

For the study, doctors recruited RA patients who were on methotrexate, or who were getting ready to start methotrexate treatment. Blood samples were analyzed to determine how methotrexate normalizes the levels of certain genes and proteins in immune system cells.

As blood cells from RA patients grow and divide, those cells show signs of stress and aging. The results of these studies suggest that methotrexate suppresses the immune system and also changes an immune cell’s profile, making the cell more normal.

The researchers are also looking for activation of immune pathways in the blood samples. This information will help them reconstruct the likely pathways of action for methotrexate.

It is possible that the blood tests will show changes before a patient sees improvement, which would help doctors predict treatment outcomes and assess how a patient would react to the drug. No blood test currently exists to determine how a patient will react to methotrexate.

Dr. Olsen says the Foundation grant gave her the initial push she and her colleagues needed to move their research forward. They are now working on a new set of methotrexate-related research proposals.