Exploiting Leading Edge 7T MRI Brain Imaging to Decipher Olumiant's Mode of Analgesic Action in Rheumatoid Arthritis

The revolution in treatments for rheumatoid arthritis (RA) has transformed patient outcomes, but many patients continue to experience life disabling pain. Even those who achieve full disease remission with state-of-the-art treatments report substantially higher levels of pain when compared to the general population. Researchers believe this disconnect is due to the existence of pain sources that are in addition to those present in the joints. In particular, the central nervous system (CNS) may have an important role in determining RA pain. According to a recent study, RA patients who received treatment with Olumiant (a Janus Kinase (JAK) inhibitor that works by interfering with the inflammatory processes that lead to the symptoms of RA) reported better and quicker pain improvements compared to those receiving other types of therapy. However, this could not be explained by levels of peripheral inflammation alone and remains to be fully understood. Investigators think this improvement may be related to the role of the JAK pathway in the brain and that inhibition of this pathway with Olumiant could normalise brain connectivity in respect to pain processing. Advanced brain scanning methods have already helped to identify specific regions of the brain that are thought to be important in pain processing and peripheral inflammation; a) enhanced functional connectivity between the Default Mode Network (DMN) and insula and b) enhanced functional connectivity between the Dorsal Attention Network (DAN) and the left inferior parietal lobule (LIPL). This study aims to elucidate the mechanisms of analgesic action of Olumiant by examining changes in functional connectivity and glutamate levels within the CNS and exploring the relationship between MRI markers, pain, clinical phenotype and peripheral immune markers.