ObjectiveTo evaluate the ability of fluorescence optical imaging (FOI) Xiralite in the discrimination between rheumatoid arthritis (RA) patients with and without need of rituximab (RTX) retherapy—in comparison to clinical, laboratory and musculoskeletal ultrasound parameters.Patients and methodsPatients with established RA were prospectively followed over 1 year by Disease Activity Score 28, patient’s global disease activity (visual analogue scale 0–100 mm), C reactive protein and erythrocyte sedimentation rate, ultrasound seven joint (US7) score and FOI in phases 1–3 and automatically generated PrimaVista mode (PVM) at baseline (before RTX) and after 3, 6 and 12 months. The need for RTX retherapy was decided by the treating rheumatologist—blinded to imaging data.Results31 patients (female 77.4%, mean age 60.1±11.4, mean disease duration 14.9±7.1 years) were included. Fourteen (45.2%) patients received RTX retherapy within 12 months. In the group with RTX retherapy, FOI in PVM mode was the only parameter that presented significant increase over time (β: 0.40, 95% CI: 0.08 to 0.71, p=0.013)—compared with the group without retherapy. In the prediction model via ROC analysis, FOI in PVM reached the highest values of all imaging, clinical and laboratory parameters which was associated with retherapy over 1 year with an area under the curve (AUC) of 0.78 (OR: 0.84, 95% CI: 0.72 to 0.98, p=0.031). US7 GS synovitis score revealed similar association with an AUC of 0.73 (p=0.049).ConclusionUS7 GS synovitis score and FOI in PVM are able to discriminate between patients with and without need for RTX retherapy better than clinical and laboratory parameters.