Background/Purpose:

Although a number of studies have shown a higher sensitivity of ultrasound than clinical joint examination in detecting synovitis in patients with rheumatoid arthritis (RA), only a few studies have actually demonstrated the superiority of ultrasound to conventional measures in evaluating synovitis that causes structural damage. In this study, we aimed to demonstrate that structural damage progression is associated with time-integrated power Doppler (PD) signals more significantly than with time-integrated DAS28 in RA patients receiving methotrexate or biological agents.

Methods:

Patients with an established diagnosis of RA who required new or additional treatment with either methotrexate (MTX), TNF antagonists, or tocilizumab (TCZ) were consecutively enrolled in this study. Patients underwent clinical, laboratory, and ultrasonographic assessment at baseline and at 12 and 24 weeks of follow-up. Patients also underwent radiographic assessment at baseline and at 24 weeks. A systematic multiplanar ultrasound examination of 28 joint regions was performed and gray-scale (GS) synovitis and PD signals were recorded with semi-quantitative scores (0-3).

Results:

Forty-eight RA patients were enrolled. All 17 patients in MTX group were treated with MTX alone, whereas 20 out of 23 patients in TNF group and all eight patients in TCZ group received combination therapy with MTX. Changes in DAS28 and CDAI significantly correlated with those in total GS and PD scores between baseline and 12 weeks. The absolute values of standardized response means (SRM) for total PD scores between baseline and 12 weeks tended to be larger (TNF antagonists, 1.43; TCZ, 1.93) than those for DAS28 (TNF antagonists, 1.39; TCZ, 1.71), CDAI (TNF antagonists, 1.07; TCZ, 1.03), or total GS scores (TNF antagonists, 1.40; TCZ, 0.86) in patients treated with biological agents. When time-integrated disease activity was calculated by summing scores at three visits, the correlation between time-integrated total PD scores and changes in total Sharp scores during 24 weeks was statistically significant, whereas the correlations between time-integrated DAS28 or total GS scores and changes in total Sharp scores were not statistically significant. In sub-group analyses for each treatment regimen, time-integrated total PD scores significantly correlated with changes in total Sharp scores in patients treated with MTX alone, but not in those treated with TNF antagonists (Figure).

Conclusion:

PD ultrasound represents synovitis activity that causes joint damage progression more directly than DAS28 or GS synovitis does. The lack of correlation between time-integrated total PD scores and changes in total Sharp scores in patients treated with TNF antagonists may reflect the protective effect of TNF antagonists against joint damage that is independent of synovitis activity.