Rheumatoid arthritis: Early immune changes during methotrexate treatment may predict treatment success
Researchers at the Medical University of Vienna have shown that methotrexate (MTX), the standard first-line treatment for rheumatoid arthritis, induces coordinated changes in the immune system within just a few weeks after treatment begins. The study identified early cellular and molecular signatures that may help predict whether patients will respond successfully to therapy. The findings were published in the Annals of the Rheumatic Diseases.
The research combined single-cell RNA sequencing with advanced immunophenotyping to monitor changes in immune cell populations and molecular signalling pathways from the start of methotrexate treatment. The study was conducted by researchers from the Division of Rheumatology at the Department of Medicine III, Medical University of Vienna, together with collaborators from Sweden and Germany.
Early immune response to methotrexate
The researchers followed patients with rheumatoid arthritis who had not previously received treatment during the first twelve weeks of methotrexate therapy. Significant changes in the immune system were already detectable after three weeks, well before clinical improvements became apparent.
Among the most important findings was a reduction in T follicular helper (Tfh) cells and plasmablasts, specialised antibody-producing B cells. These immune changes were primarily observed in patients who later responded well to treatment, whereas patients who did not respond showed only limited changes in these cell populations.
New insights into the mechanism of action
In addition to changes in immune cell populations, the study identified extensive molecular reprogramming of the immune system and revealed previously unrecognised signalling pathways associated with methotrexate therapy. Laboratory experiments also demonstrated direct effects of methotrexate on the development of plasmablasts, providing new insights into the biological mechanisms underlying one of the most widely used treatments for rheumatoid arthritis.
Potential for personalised treatment
The findings suggest that early biological changes in the immune system could serve as biomarkers for predicting treatment success. Such markers may allow clinicians in the future to identify patients who are likely to benefit from methotrexate at an early stage, while enabling non-responders to be switched more rapidly to alternative treatment strategies. The study provides one of the most comprehensive analyses to date of the early immune response to methotrexate and offers a foundation for future personalised treatment approaches in rheumatology.