POS0310 BARICITINIB MAY REDUCE CO-EXISTING FIBROMYALGIA IN PEOPLE WITH RHEUMATOID ARTHRITIS: AN ULTRA-HIGH RESOLUTION MRI BRAIN STUDY
Authors: N. Basu, S. Al-Wasity, J. Brock, K. Stefanov, F. Sunzini, N. Aldehmi, M. Arnott, D. Porter, G. Keith, C. Kaplan, A. Schrepf, I. B. Mc Innes, D. Clauw
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Multiple mechanisms underly the major burden of rheumatoid arthritis (RA) pain. The high prevalence of co-existing fibromyalgia (FM) supports the contribution of central nervous system associated nociplastic pain pathways. In RA, we previously employed functional MRI (fMRI) brain to objectively demonstrate nociplastic pain (hyperconnectivity between Default Mode Network [DMN] and Insula). In addition, among those with co-existing FM, we observed a significant relationship between peripheral inflammation and brain hyperconnectivity, specifically the inferior parietal lobule (IPL, a major hub of the DMN) and Insula. We proposed that this represented a sub-type of nociplastic pain which could be modified by peripheral inflammation. However, these studies were cross-sectional and limited to 3T resolution imaging. <h3>Objectives:</h3> To evaluate if baricitinib, an effective mediator of peripheral inflammation in RA, subjectively and objectively reduces nociplastic pain, employing for the first time ultra-high resolution (7T) MRI. <h3>Methods:</h3> A longitudinal, observational study of moderate to severe RA patients newly prescribed baricitinib by their standard care rheumatologist. Pre-treatment, participants were clinically evaluated, including completion of the ACR FM survey criteria (a validated subjective measure of nociplastic pain, range 0-31). They then undertook an ultra-high resolution (7T) MRI brain scan, which yields superior reserves of power and so enables smaller sample sizes. A simultaneous-multi-slice (SMS) echo-planar imaging (EPI) sequence was employed to capture resting state fMRI. The same measures were collected at a follow-up study visit (12±2 weeks). MRI data were pre-processed and analysed using the functional connectivity toolbox (CONN) v19.c, based on Statistical Parametric Mapping and MATLAB (R2019a). Seed-based connectivity analyses were adopted to calculate the connectivity maps informed by our <i>a priori</i> determined regions of interest (DMN-Insula and IPL-Insula). Simple descriptive statistics were applied to estimate significance of change between study visits. <h3>Results:</h3> Pre-treatment, the mean ACR FM score of the n=13 participants (mean age 58.0 years, 69% female) was 14.2± 5.2, reducing to 10.5±7.2 (p=0.03) at follow-up. Of the 10 subjects with complete longitudinal fMRI data, there was a significant reduction in connectivity between the DMN and posterior insula (p=0.037) (Figure 1). Furthermore, there were similarly significant reductions between the IPL and anterior/middle insular regions (p=0.016 and p=0.03, respectively). <h3>Conclusion:</h3> Baricitinib significantly reduced both subjective and objective measures of nociplastic pain. The mechanism of action appears to be mediated through nociplastic brain functional connections previously implicated with peripheral inflammation. Although the specificity of these effects is unknown given the uncontrolled study design, these data provide further evidence that nociplastic pain is not a single construct and that, in the context of RA, there is a sub-type which may be modifiable by anti-inflammatory approaches. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Neil Basu Abbvie, Lilly, Vifor, Pfizer, MSD, Lilly, Galapagos, Pfizer, GSK, Galapagos, Lilly, Vifor, Salim Al-Wasity: None declared, James Brock: None declared, Kristian Stefanov: None declared, Flavia Sunzini: None declared, Norah Aldehmi: None declared, Maxine Arnott: None declared, David Porter: None declared, Graeme Keith: None declared, Chelsea Kaplan: None declared, Andrew Schrepf: None declared, Iain B. Mc Innes: None declared, Daniel Clauw: None declared.