Background/Purpose: Management of RA patients has improved in the last two decades in part with the use of ultrasound (US) in daily clinical practice. The use of US is helping to improve a tight control of RA patients and to predict clinical flares.  Those inflammatory cytokines involved in RA pathology must be related with the US findings. We therefore evaluated the relationship between US patterns and cytokine levels in RA patients before and after IL-6 blockade.

Methods: Peripheral blood was obtained from 30 RA patients, meeting the ACR criteria, that were treated with tocilizumab. In all patients, RA was refractory to treatment with DMARDs, including methotrexate. Tocilizumab treatment was begun following European and Spanish guidelines.  Plasma was collected prior to first infusion and at 1, 3, 6 and 12 months after treatment. Laboratory analysis included haemogram, ESR, CRP, RF, ACPAs, IL-17, IL-22, VEGF, IL-6 and sIL-6R. US assessment was registered for each visit for 32 joints and 12 tendons of hands and feet in Gray Scales (GS) and Power Doppler (PD) using a semiquantitative scale (0-3 points). Clinical data collected was DAS28, SDAI and CDAI.

Results: Clinical and demographic baseline data of the patients is shown in table 1. We have found two groups of patients based on the baseline PD values (group 1: 18,9±5,9 vs group 2: 4,8±4,05) As expected, patients in group 1 also had higher GS (group 1: 36,2±14 vs group 2: 12,6±9,8) and DAS28 values (group 1: 6,38±0,69 vs group 2: 5,44±0,9) (Figure 1). Baseline PD correlated with plasmatic IL-17 (R=0,39; p=0,045) and IL-22 concentration (R=0,554; p=0,002), but not with other cytokines. IL-17 and IL-22 were correlated at baseline (R=0,913; p<0,001). IL-17 and IL-22 also correlated with RF titers (R=0,795; p<0,001 and R=0,67; p<0,0001) and VEGF (R=0,935; p<0,001 and R=0,784; p<0,001) values. After 12 months of treatment, we found significant changes in PD (11,81±9 vs 1,76±3,6), GS (25,36±17 vs 4,38±6,8), DAS28 (5,76±0,9 vs 2,8±1,4), IL-6R (447±368 vs 1892±960 ng/ml) and IL-22 (3107±5700 vs 5983±12022 pg/ml). There were no changes in IL-6 (819±896 vs 896±906 pg/ml), IL-17 (1677±3900 pg/ml) and VEGF (849±2115 vs 796±2016 pg/ml) plasmatic concentrations. After 12 months of tocilizumab PD values correlated with IL-17 (R=0,446; P=0,02) and VEGF (R=0,599; p<0,001) concentrations.

Conclusion: There is a correlation at baseline between PD and IL-17 and IL-22. After 12 months of IL-6 blockade there is a significant improvement in clinical and US values without changes in levels of IL-17, IL-6 and VEGF. IL-17 was the only cytokine that correlated with PD levels throughout the study.