Arthritis Patients In Clinical Remission Research Articles

Does tenosynovitis of the hand detected by B-mode ultrasound predict loss of clinical remission in rheumatoid arthritis? Results from a real-life cohort.

ObjectiveThe role of US-detected tenosynovitis (USTS) in the management of rheumatoid arthritis remains controversial. The aim of this study was to investigate whether tenosynovitis can predict a flare in rheumatoid arthritis patients in remission in a real-life cohort.MethodsRheumatoid arthritis patients from the Swiss Clinical Quality Management cohort were included in this study if they were in clinical remission, defined by 28-joint disease activity score (DAS28-ESR) <2.6, and had an available B-mode tenosynovitis score. The patients were stratified according to the presence or absence of tenosynovitis (USTS+ vs. USTS–). Cox proportional hazard models were used for time-to-event analysis until the loss of remission, after adjustment for multiple confounders. The impact of baseline US performed early in remission and the advent of flares at different fixed time periods after baseline were investigated in sensitivity analysis.ResultsTenosynovitis was detected in 10% of 402 rheumatoid arthritis patients in remission. At baseline, USTS+ patients in remission had significantly higher DAS28-ESR (mean (SD): USTS– 1.8 (0.5) versus USTS+ 2.0 (0.5); p = 0.0019) and higher additional disease activity parameters, such as physician global assessment, and simplified- and clinical-disease activity index. Joint synovitis detected by B-mode US was associated with tenosynovitis (mean (SD) 7.2 (6.3) in USTS– versus 9.0 (5.4) in USTS+, respectively; p = 0.02). A disease flare was observed in 69% of remission phases, with no differences in the time to loss of remission between USTS+ and USTS– groups.ConclusionWhile US-detected tenosynovitis was associated with higher disease activity parameters in rheumatoid arthritis patients in clinical remission, it was not able to predict a flare.

Ultrasound-detected tenosynovitis as a risk factor for flares in rheumatoid arthritis patients in clinical remission.

Our objective was to investigate the value of ultrasound (US) detected synovitis and tenosynovitis as risk factors for short term flare in rheumatoid arthritis (RA) patients in clinical remission. Consecutive RA patients in clinical remission (DAS28 ERS < 2.6) for at least 3months underwent Power Doppler ultrasound (PDUS) examination of 1st to 6th extensor compartments at the wrist, 2nd to 5th finger flexor, posterior tibial tendon, and peroneal tendons. To assess synovitis, carpal joints, 1st to 5th metacarpophalangeal (MCP) joints, and 2nd to 5th interphalangeal proximal (IPP) joints were bilaterally examined. Synovitis and tenosynovitis were defined according to OMERACT. Patients were followed for 1year. Disease flare was defined as an increase in disease activity generating the need for a change in therapy by the attending rheumatologist. Ninety patients were included. After 1year of follow-up, 26 patients (29%) experienced a flare. At baseline 39%, 23% and 8% had US-detected synovitis, tenosynovitis or both, respectively. In the 1-year period after the baseline US examination, US-detected tenosynovitis (RR: 4.9; 95% CI: 2.2-10.8) was associated with an increased risk of exacerbation. This association was not shown with US-detected synovitis (RR: 1.3; 95% CI: 0.76-2.2). In the multivariate analysis, only subclinical tenosynovitis (OR: 9.8; 95% CI: 2.5-39.1; p = 0.001) and baseline DAS28 (OR: 5.7; 95% CI: 1.1-31.6; p = 0.047) were significantly associated with an increased risk of having a flare. In our study, subclinical tenosynovitis was associated with disease flare in patients with RA in clinical remission. • Synovitis and tenosynovitis are risk factors for short term flare in RA patients in clinical remission. • Subclinical tenosynovitis, but not synovitis, was associated with disease flare in patients with unstable remission. • Ultrasound-detected tenosynovitis could be useful to predict relapses in RA patients in clinical remission.

Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial

Objectives: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. Method: One-hundred patients with established RA, Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as ‘in clinical remission’) who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0–2.6), HAQ score (0.08, 0.03–0.1), MRI combined inflammation (2.5, 0.9–4.1), and SDAI scores (2.7, 1.9–3.5). Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. Trial registration: Clinicaltrials.gov identifier: NCT01656278

Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission.

To assess the ability of ultrasoundto predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0-3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10-0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up-the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

Subclinical synovitis measured by ultrasound in rheumatoid arthritis patients with clinical remission induced by synthetic and biological modifying disease drugs

BackgroundRheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. ObjectiveTo determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. MethodsHospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. ResultsOut of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. ConclusionsPersistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission.

The Evaluation of Serum Tumor Necrosis Factor-Like Weak Inducer of Apoptosis, Interleukin-6, Fetuin-A, Homeostatic Model Assessment-Insulin Resistance, and Insulin Levels in Rheumatoid Arthritis Patients in Clinical Remission

The Evaluation of Serum Tumor Necrosis Factor-Like Weak Inducer of Apoptosis, Interleukin-6, Fetuin-A, Homeostatic Model Assessment-Insulin Resistance, and Insulin Levels in Rheumatoid Arthritis Patients in Clinical Remission

Power Doppler ultrasound in the evaluation of hand joints in rheumatoid arthritis patients in clinical remission: Association with composite index scores and functional status

BackgroundEvaluation of remission in Rheumatoid Arthritis (RA) largely relies on composite scores based on clinical and laboratory assessments however, patients can fulfill clinical remission criteria as defined by composite scores, yet still have evidence of synovitis detectable on imaging. Aim of the workTo evaluate hand and wrist joints in patients with RA in clinical remission using power Doppler (PD) ultrasonography and to study the association between ultrasonographic findings and composite index scores. Patients and methodsThis study was conducted on 50 RA patients in clinical remission. Ten matched healthy subjects were included as control. The modified health assessment questionnaire (MHAQ) was assessed in the patients; disease activity was calculated using a composite index score including disease activity score (DAS28) and clinical disease activity index (CDAI). Ultrasonographic assessment of the hand and wrist joints was performed. ResultsThe mean age of the patients was 50.9 ± 9.2 years, disease duration was 10.6 ± 5.5 years and were 38 females and 12 males. The mean DAS28 was 2.3 ± 0.3. On ultrasonographic examination, 14 (28%) patients had normal synovium, while 18 (36%) showed synovial hypertrophy without evidence of inflammation and 18 (36%) had PD signals. DAS28 was higher in patients with PD signals (2.36 ± 0.3) compared to those without synovitis (2.3 ± 0.28). There was a significant correlation between PD activity and CDAI (p = 0.005), MHAQ (p = 0.002) and disease duration (p = 0.023). ConclusionPower Doppler ultrasound can detect residual inflammation in RA patients in clinical remission and its scores were signficantly associated with the clinical disease activity index and functional status.

Grade and location of power Doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor α.

To investigate power Doppler (PD) signal, grade and location and their association with radiographic progression in RA patients in remission. A prospective observational study was conducted in 125 consecutive RA patients in stable 28-joint DAS (DAS28) remission (⩾6 months) achieved on anti-TNF-α. At baseline, patients in stable remission underwent radiographic and US examination of the wrists and MCP, PIP and MTP joints. Semi-quantitative PD scoring (0-3) was recorded. We scored PD according to two locations: capsular or within synovial tissue without bone contact (location 1) and with bone contact or penetrating bone cortex (location 2). Radiographic progression was evaluated at the 1 year follow-up and defined as a change in van der Heijde-modified total Sharp score >0. Risk ratios (RRs) of radiographic progression according to presence, grade and location of PD were calculated. Four patients were excluded because of missing data. At baseline, 59/121 (48.7%) patients had a PD signal in one or more joints. PD location 2 was found in 74.6% patients (44/59). At the 1 year follow-up, 17/121 patients experienced radiographic progression: all had PD signal in one or more joints at baseline (RR 2.47, P < 0.0001). Radiographic progression was associated with the following baseline US features: PD grade 2 (RR 4.58, P < 0.01), PD grade 3 (RR 3.49, P < 0.05), total PD score ⩾2 (sum of all PD scores) (RR 3.19, P < 0.0001) and PD location 2 (RR 3.49, P < 0.0001). Higher PD grades and PD in contact with/or penetrating bone are associated with radiographic progression in patients in DAS28 remission.

Immunopathologic characterization of ultrasound-defined synovitis in rheumatoid arthritis patients in clinical remission.

BackgroundPatients with rheumatoid arthritis (RA) in clinical remission may have ultrasound-defined synovitis according to the presence of power Doppler (PD) signal. The objective was to describe the immunopathologic characteristics of ultrasound-defined synovitis compared with synovitis in patients with clinically active RA.MethodsWe included between 6 and 8 ultrasound-guided synovial biopsies per patient from 20 patients with RA in clinical remission (DAS28-ESR <2.6) with PD signal, 22 synovial tissue samples (ST) from patients with clinically active RA (swollen joint with confirmed inflammatory synovial fluid) as inflammatory controls, and 10 ST from non-inflammatory controls. Immunostaining for CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD117 (mast cells), hsp47 (fibroblasts), bFGF and CXCL12 (angiogenic factors) was made and quantified by digital image analysis. The number of CD31 vessels/mm2 was quantified.ResultsRA patients in remission with PD signal had significantly reduced synovial T-cell, B-cell, mast cell and fibroblast density, but similar macrophage infiltration compared with patients with clinically active RA. Vascularity, bFGF and CXCL12 were partially reduced in RA patients in remission with PD signal compared to those with active RA, but were significantly higher compared with ST from non-inflammatory controls. During the 12-month follow up, 8/20 RA patients (40 %) lost remission: all had synovial hypertrophy grade ≥2 and significantly more synovial B cells and mast cells than patients maintaining remission.ConclusionsAsymptomatic ultrasound-defined synovitis and clinically active arthritis differ in the degree of infiltrating lymphoid, mast cells and fibroblast density, but are similar with respect to macrophage infiltration. Persistently increased angiogenic factor expression and vascularity may explain the persistence of a PD signal.

Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis.

The aims of this study were to assess the prevalence of US-detected residual synovitis in patients with RA in clinical remission (CR) and evaluate its predictive value for relapse and structural progression. We performed a systematic literature search of Medline, Embase and rheumatology meeting databases from 1 January 2001 to 28 May 2012. The prevalence of US grey-scale (USGS) signals (synovial hypertrophy or joint effusion) and power Doppler (PD) signals were collected, taking into account CR definitions [44-joint DAS (DAS44), 28-joint DAS (DAS28), SDAI, ACR 1981 or ACR/European League Against Rheumatism 2011], stage of RA (early or long-standing) and US examination (from 5 to 44 joints assessed). A meta-analysis assessing the risk of relapse or structural progression in patients with synovitis involved the Mantel-Haenszel method. We included 19 studies of 1618 patients, 1369 in remission. The prevalence of USGS positive (USGS+), USGS+/PD negative (PD-), USGS+/PD positive (PD+) and USGS negative (USGS-/PD- was 84%, 41%, 44% and 15%, respectively. The prevalence of USGS+ or USGS+/PD+ was comparable among CR definitions and US methods. The prevalence of USGS+ and USGS+/PD+ was greater for long-standing than early RA (P < 0.001). Meta-analyses of five studies (271 patients), three studies (173 patients) and two studies (798 joints) revealed an association of USGS+/PD+ and risk of relapse [odds ratio (OR) 3.2 (95% CI 1.8, 5.9), P = 0.0001, I(2) = 0%] and structural progression in individual patients [OR 9.13 (95% CI 1.1, 74.3), P = 0.04, I(2) = 43%] and joints [OR 6.95 (95% CI 3.4, 13.9), P < 0.0001, I(2) = 6%] over 1-2 years. US-detected residual synovitis is frequent and predicts the risk of relapse and structural progression in RA patients with CR.

FRI0276 Ultrasonography as Useful Tool to Identify Rheumatoid Arthritis Patients in Clinical Remission for Tapering or Withdrawal TNFA Blockers without Disease Relapse

BackgroundUltrasonography (US) has superior sensitivity in detecting the presence of synovial hypertrophy (SH) and its activity by Power Doppler (PD) in Rheumatoid Arthritis (RA). The relapse rate is nearly 50%...

SAT0157 Discontinuation of etanercept in rheumatoid arthritis patients in clinical remission: Two-year outcome

BackgroundTumor necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after achievement of clinical remission is important for safety...

AB0723 Subclinical ultrasound synovitis in a particular joint is associated with ultrasound evidence of bone erosions in the same joint, in patients with rheumatoid arthritis in clinical remission

Objectivesthe aim of the present study was to investigate the relationship between ultrasound (US) findings indicative of joint inflammation and both clinical and US features characterizing synovitis at joint level...