Fig. 1

Study design. a Samples used for biomarker discovery and validation. A subset of patient samples from the SERA Inception Cohort (86 RA patients and 34 HC) were used to discover and validate the MTX response biomarker. b Workflow for discovery and validation of the epigenetic stratifying biomarker. For Stage I and Stage II biomarker discovery and testing, clinical samples from MTX-treatment naïve patients were provided after confirmation of response by SDAI. In Stage I, an initial panel of 13,322 potential biomarkers was refined to a 5-marker chromosomal conformation signature (CCS). In Stage II, the disease specific nature of the biomarker panel was confirmed by stratification against HC and further testing was performed on 59 RA patients (29 R and 30 NR) and 30 HC. Final validation of the biomarker panel was done on an independent, blinded cohort of 19 RA patients