Subclinical Synovitis Assessed by Ultrasound Predicts Flare and Progressive Bone Erosion in Rheumatoid Arthritis Patients with Clinical Remission: A Systematic Review and Metaanalysis

Objective. Subclinical synovitis can be detected by ultrasound in patients with rheumatoid arthritis (RA) who are in clinical remission. We aimed to confirm its predictive value for flare and progressive bone erosion. Methods. A systematic literature search was performed in Pubmed, Web of Science, Embase, and Cochrane Library on September 7, 2014. Baseline clinical and ultrasonographic characteristics were collected. Methodological quality was assessed. Pooled OR were calculated using Mantel-Haenszel model. We explored the source of heterogeneity through subgroup analysis and completed a cumulative metaanalysis. Results. Thirteen articles were included (8 with flare, 4 with bone erosion, 1 with both flare and bone erosion). Metaanalysis revealed an association between power Doppler (PD) positivity and the risk of flare (OR 4.52, 95% CI 2.61-7.84, p < 0.00001, I-2 = 21%), the risk of progressive bone erosion on patient level (OR 12.80, 95% CI 1.29-126.81, p = 0.03, I-2 = 52%) and the risk of progressive bone erosion on joint level (OR 11.85, 95% CI 5.01-28.03, p < 0.00001, I-2 = 0%). Further subgroup analysis showed a higher risk of flare in patients with a study period < 1 year (OR 19.98 vs 3.41). No significant differences were observed in the subgroup analysis in duration of remission, disease duration, and medications. Moreover, cumulative metaanalysis indicated the validation and an increasing accuracy of PD positivity in predicting flare since 2012. Conclusion. Ultrasound-detected subclinical synovitis can predict the risk of flare and progressive bone erosion in RA patients with clinical remission. Additionally, the flare of RA tends to occur within a followup of 1 year.