Chu SH, Cui J, Sparks JA, et al. - This study assessed for metabolic variations prior to rheumatoid arthritis (RA) onset applying a large non-targeted metabolomics platform to distinguish novel pathways and advance understanding of RA development. Researchers matched 254 incident RA cases with plasma samples drawn pre-RA onset in the Nurses’ Health Study (NHS) cohorts in 1:2 ratio to 501 controls on age, race, menopause/post-menopausal hormone use and blood collection features. Associations between metabolites and incidence of RA were analyzed by conditional logistic regression analyses, adjusted for age, smoking and BMI, accounting for multiple comparisons. Seropositive (sero+) RA and RA within 5 years of sample collection were tested by subgroup analyses. They evaluated significant metabolites in a female military pre-RA case–control study (n = 290). Among women, several metabolites were inversely correlated with incidence of RA. It was indicated that three short-chain acylcarnitines replicated in a smaller dataset and may reflect inflammation in the 5-year period prior to sero+RA diagnosis.