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Abstract Background Optical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up. Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers. Methods 1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses. Results OST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83–0.94) and after GC=0.811(95%CI=0.74–0.881); p