POS0601 CLUSTER ANALYSIS OF SERUM FATTY ACIDS IDENTIFIES DIFFERENT DISEASE TRAJECTORIES IN EARLY RHEUMATOID ARTHRITIS: RESULTS FROM THE FRENCH ESPOIR COHORT
Authors: J. Sigaux, R. Elodie, M. Boubaya, A. Cantagrel, R. M. Flipo, M. C. Boissier, L. Semerano
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Long-chain fatty acids (FAs) of the n-3 and n-6 families may modulate inflammatory processes and be involved at different levels in the pathophysiology of rheumatoid arthritis (RA). We have previously shown that in early RA, a serum lipid profile rich in n-3 FAs at baseline was independently associated with reduced disease activity over 6 months. However, it is still unclear whether stratification of patients according to their profiles of serum FAs predicts different disease trajectories in the early phases of the disease. <h3>Objectives:</h3> To assess the baseline and longitudinal (6- and 12-month) associations of serum FAs clusters with disease activity in a national cohort of early RA. <h3>Methods:</h3> FAs were quantified by gas chromatography-mass spectrometry (GC/MS) in the serum of 611 patients with early RA drawn at inclusion in the French cohort Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR). Unsupervised hierarchical cluster analysis on principal components analysis was performed using the levels of 19 serum FAs with 14 to 22 carbon atoms including saturated (n0) and polyunsaturated (n3, n6, n7, n9) FAs, identifying four distinct clusters: <b>Cluster 1</b>: Characterized by higher concentrations of long-chain n-3 FAs (EPA, DHA, DPA) but also containing a fair amount of the n-6 arachidonic acid. <b>Cluster 2:</b> Dominated by higher levels of the n-6 FA linoleic acid. <b>Cluster 3:</b> Exhibiting a signature characterized by high levels of n-0, n-7 and n-9 FAs with very little long-chain n-3 FAs. <b>Cluster 4:</b> Closely related to Cluster 3 regarding n-0, n-7 and n-9 FAs levels, with slightly higher levels of long-chain n-3 and n-6 FAs than Cluster 3. The association of FAs clusters with baseline variables was tested at univariate analysis. The association with 6- and 12-month disease activity (with active disease defined as DAS28-ESR&gt;3.2) was tested with negative binomial regression analysis, including baseline C-reactive protein (CRP), baseline DAS28-ESR, corticosteroid and DMARD treatments (conventional or biologic) between 0 and 6 or 12 months, anti-citrullinated protein antibodies (ACPA) status, and baseline Total Sharp Score as covariates. Cluster 3 (the cluster with the numerically highest DAS28 level at 6 months) was used as the reference. <h3>Results:</h3> Baseline univariate analysis revealed associations between Cluster 1 and Cluster 2 with lower CRP levels (p=0.02) and lower DAS28-ESR scores (p&lt;0.05). Additionally, participants in these clusters demonstrated lower BMI and triglyceride levels (all p&lt;0.05). Multivariable analysis revealed significant associations between baseline DAS28, baseline fatty acid patterns, treatments, ACPA positivity, and baseline Total Sharp Score with 6-month DAS28 disease activity. Specifically, when compared to Cluster 3, Clusters 1 demonstrated lower odds of having active disease (OR 0.5 [0.29-0.87] (p=0.015) (Table 1). The association persisted at 12 months for Cluster 1, which was still associated with a reduced risk of having active disease (DAS28&gt;3.2) with an odds ratio of 0.53 [0.3-0.92] (p=0.025). <h3>Conclusion:</h3> This study, involving patients with early RA from the French cohort ESPOIR, shows that patients with a particular cluster of serum FA enriched in long chain n-3 FAs are at lower risk of having active disease during the first year of observation in the cohort. While causality cannot be formally inferred, these findings suggest the potential influence of FAs clusters, in conjunction with other variables, on the clinical trajectory of RA. Tailored nutritional interventions targeting Cluster 1 may help to shape a more favorable disease course in RA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>