Patients and study design
Altogether, 300 patients with RA who underwent MSUS and attended our hospital for routine care were enrolled in the study; cross-sectional analysis by disease activity was performed for the patients. Patients with RA > 20 years of age who received at least one disease-modifying antirheumatic drug (DMARD) continuously for at least 24 weeks were included. All patients underwent US scanning for arthritis evaluation and were diagnosed with RA according to the 1987 American Rheumatism Association revised criteria or the 2010 American College of Rheumatology/EULAR classification criteria [8,9,10].
Demographic and clinical characteristics were obtained from medical records, including age, sex, disease duration, oral steroid use, methotrexate (MTX) use, biological (targeted synthetic) (b[ts]) DMARD use, tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, matrix metalloproteinase-3 (MMP-3) level, rheumatoid factor, anti-cyclic citrullinated peptide antibody level, and PROs (morning stiffness, pain visual analog scale [VAS] score, and fatigue VAS score).
The objective of this study was to investigate the residual symptoms and residual synovitis due to remission (REM) or (LDA). The study and its retrospective observation design was approved by the Ethics Committee of the Japan Physicians Association, and informed consent was obtained from all patients. The research was conducted in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects.
Treatment
Treatment involved the use of conventional synthetic DMARDs, including MTX. b(ts)DMARDs were prescribed to patients with RA who did not respond adequately to conventional synthetic DMARD therapy according to the guidelines of the Japan College of Rheumatology.
Ultrasonography
Clinical assessment by US scanning was performed bilaterally at identical time points for the wrist (intracarpal, radiocarpal, and ulnocarpal recesses), first to fifth metacarpophalangeal joints, first interphalangeal joints, and second to fifth proximal interphalangeal joints (dorsal recess) by a single-trained sonographer (S.K.) with 10 years of experience, using MSUS.
The MSUS examinations were performed with TOSHIBA Aplio 300 ultrasound machines (Toshiba Medical Systems Corp., Otawara, Japan) using a linear transducer (12 MHz). No changes in the US settings were made during the study, and no software was upgraded.
Systematic multiplanar grayscale (GS) US and power Doppler (PD) US examinations were performed on 22 joints in a standardized manner based on the EULAR guidelines [11]. Each joint was scored using a semiquantitative scale of 0–3 for GS, defined as follows: grade 0, absence of synovial hypertrophy on GS, no synovial thickening; grade 1, mild or minimal synovial thickening filling the angle between the periarticular bones without bulging over the line linking the tops of the bones; grade 2, moderate synovial thickening bulging over the line linking the tops of the periarticular bones, but without extension to at least one bone diaphysis; and grade 3, marked synovial thickening bulging over the line linking the tops of the periarticular bones and with extension to at least one of the bone diaphysis. The semiquantitative scale of 0–3 for PD [12] was as follows: grade 0, no PD signal and no synovial flow; grade 1, mild, single-vessel signal; grade 2, moderate, confluent signal in less than half of the synovial area; and grade 3, marked PD signal in more than half of the synovial area. The US score was calculated as the GS score and PD score (range, 0–66), respectively.
Clinical assessment
Disease activity was assessed using the Simplified Disease Activity Index (SDAI) [13, 14]. Functional impairment was assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI) [15]. Quality of life (QoL) was assessed using the European Quality of Life-5 Dimensions (EQ-5D-5L) questionnaire [16]. Responses to the EQ-5D-5L were converted to a QoL score using Japanese value sets [17].
Statistical analyses
We assessed the correlations between clinical and US variables. We performed multivariate analysis by dividing the data by disease activity. We first divided the analysis into two groups: those who achieved LDA and those who did not. Next, we divided the analysis into REM and LDA. Finally, we analysed each PRO in the obtained US results. A univariate analysis was performed using the Wilcoxon signed-rank test and likelihood ratio test. P < 0.05 was considered statistically significant. To identify independent variables, a multivariate logistic regression analysis of variables that were significant in the univariate analysis was performed using the stepwise method.
To perform stratified analyses of GS scores (focused on the presence or absence of GS score ≥ 2 identified by multivariate analysis), the Wilcoxon signed-rank test was used to evaluate the relationship between the presence or absence of GS findings and each PRO. All analyses were conducted using JMP version 11.0 (SAS Institute Inc, Cary, NC, USA).