Our outcomes of interest are: 1) the presence versus absence of RA (we compare RA to HC to gain insight into factors associated with susceptibility to RA); 2) disease activity at a single point in time (we compare patients with various levels of active synovitis and inflammation); and 3) treatment response (we compare a group of patients before and after treatment with MTX or TNFi).

To determine which signaling pathways are associated with RA, we applied SCNP to RA and HC samples from Cohort 1, TT0 and T6M. To study signaling pathways associated with RA disease activity, we compared SCNP profiles from RA patients (TT0) who were starting MTX or TNFi for clinically indicated reasons. DAS28 was used to determine disease activity of Cohort 1, baseline TT0 and follow up T6M (6 months after initiation of treatment;). The DAS28 score is a continuous score that describes the degree of activity of RA. The number of swollen joints and tender joints were counted using the 28 version of simplification of original 44 joints score and the ESR, a measure of inflammation, was assayed in the local lab of each patient. We used the DAS28 with 3 variables to calculate the Modified Disease Activity Score (DAS) as follows: (0.56*sqrt (TENDER) + 0.28*sqrt (SWELL) + 0.70*ln (ESR))*1.08 + 0.16. The DAS28 score can be used to categorize patients into those with high (> 5.1), moderate (3.2 < DAS28 ≤ 5.1), or low disease activity (2.6 < DAS28 ≤ 3.2) or remission (< 2.6) [24].

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