Arthritis In Clinical Remission Research Articles

Persistence of power Doppler ultrasonography-detected synovitis over 1 year of follow-up predicts poor prognosis in rheumatoid arthritis in clinical remission: the SONORE prospective longitudinal study

Objectives(1) To assess the progression of ultrasonography-detected synovitis in a cohort of patients with rheumatoid arthritis (RA) in remission during 1 year of follow-up (2) to evaluate the ability of...

Long-term efficacy of a 2-year MRI treat-to-target strategy on disease activity and radiographic progression in patients with rheumatoid arthritis in clinical remission: 5-year follow-up of the IMAGINE-RA randomised trial

ObjectiveTo investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA)...

Predictive Value of Magnetic Resonance Imaging in Patients With Juvenile Idiopathic Arthritis in Clinical Remission.

To define the prevalence of subclinical synovitis on magnetic resonance imaging (MRI) in a large cohort of patients with juvenile idiopathic arthritis (JIA) in clinical remission and to evaluate its predictive value in terms of disease flare and joint deterioration. Ninety patients with clinically inactive JIA who underwent a contrast-enhanced (CE)-MRI of a previously affected joint were retrospectively included. Each joint was evaluated for synovitis, tenosynovitis, and bone marrow edema. Baseline and follow-up radiographs were assessed to evaluate structural damage progression. CE-MRI was acquired in 45 wrists, 30 hips, 13 ankles, and 2 knees. Subclinical synovitis was detected in 59 (65.5%) of 90 patients and bone marrow edema in 42 (46.7%) of 90 patients. Fifty-seven of 90 (63.3%) patients experienced a disease flare during follow-up. Forty-four of 59 (74.6%) patients with subclinical synovitis experienced a disease flare versus 13 (41.9%) of 31 patients with no residual synovitis on MRI (P = 0.002). The presence of subclinical synovitis was the best predictor of disease flare on multivariable regression analysis (hazard ratio [HR] 2.45, P = 0.003). Baseline and follow-up radiographs were available for 54 patients, and 17 (31.5%) of 54 patients experienced radiographic damage progression. The presence of bone marrow edema (HR 4.40, P = 0.045) and being >17 years old (HR 3.51, P = 0.04) were strong predictors of joint damage progression in the multivariable analysis. MRI-detected subclinical inflammation was present in a large proportion of patients with JIA despite clinical remission. Subclinical synovitis and bone marrow edema have been shown to play a role in predicting the risk of disease relapse and joint deterioration, with potential implications for patients' management of the disease.

Association between patient-reported outcomes and impairments in work and activity in patients with rheumatoid arthritis in clinical remission: A retrospective analysis using the IORRA database.

To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. We enrolled patients with RA ≥18 years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. The mean age of the 2614 patients was 62.4 years; 85.1% were female. Median values of the WPAI-RA score were 1.1% for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1%), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission.

Ultrasound remission in patients with rheumatoid arthritis in clinical remission.

ObjectivesThe aim of the study was to assess ultrasound (US) remission in patients with rheumatoid arthritis (RA) in clinical remission using different definitions.Material and methodsThis was a cross-sectional study including patients with RA in clinical remission defined by disease activity score (DAS28)-erythrocyte rate (ESR) ≤ 2.6 for at least 6 months. Each patient underwent B-mode and power Doppler (PD) assessments of 42 joints and 20 tendons. B-mode and PD signal for synovitis and tenosynovitis (TS) were defined and graded semi-quantitatively (0–3) according to the outcome measures in rheumatology clinical trials (OMERACT). Several different definitions of US remission were examined: the absence of synovial hypertrophy (SH), TS on B-mode and PD signal, the absence of SH and PD signal, a grade ≤ 1 of SH and the absence of PD, a grade ≤ 1 of SH and PD, the absence of PD, or a grade of PD ≤ 1. The DAS28, clinical disease activity index (CDAI), simple disease activity index (SDAI), and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were compared.ResultsThirty-seven patients were enrolled. The rate of remission according to the different composite indices was 70.2% for the SDAI, 64.8% for the CDAI, and 54% for the ACR/EULAR Boolean criteria. Synovial hypertrophy and TS in B-mode were detected in 94.6% and 40.5% of patients, respectively. Synovitis with PD signal was found in 59.5% and 13.5% of patients had TS with PD, respectively. Ultrasound remission at joints and tendons was found in 5.4–62.2% of patients. For the other remission criteria: CDAI, SDAI, and ACR/EULAR Boolean criteria, 7.7–60% of patients showed US remission at joints and tendons.ConclusionsClinical remission, even classified by strict composite indices, does not seem to be the closest method to the concept of absence of inflammatory activity; hence the interest of integrating US in assessing remission in practice.

Synovitis and Tenosynovitis on Ultrasound as Predictors of DMARD Tapering Failure in Patients with Long-Standing Rheumatoid Arthritis in Clinical Remission or Low Disease Activity.

This study aimed to investigate the predictive value of synovitis and tenosynovitis detected by grayscale (GS) and by power Doppler (PD) ultrasound (US) in relation to failure of tapering disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients. Long-standing RA patients who de-escalated treatment were included in this prospective cohort study. All patients underwent 3 ultrasonographic and clinical assessments, at baseline and every 3 or 4 months, over a period of 6-8 months. US investigation of 32 joints was performed. Synovitis was assessed by GS and PD semiquantitative scoring (0-3) and a global score was calculated for each individual by summing single joint scores. The presence of tenosynovitis was recorded whenever detected during ultrasound assessment. Thirty-three patients completed the follow-up period (29 women; 4 men). Eight patients (25%) relapsed. Using the optimal cutoff values determined by receiver operating characteristic curve, patients with a PD synovitis ≥1 at baseline had significantly greater chances to relapse than those without PD activity. During follow-up, GS tenosynovitis was detected in 6 patients (5 with PD) who failed and in 3 patients (1 with PD) who succeeded in tapering therapy. Having at least 1 joint with PD synovitis resulted in a relative risk of 3.14 and having GS tenosynovitis resulted in a relative risk of 11.4 (95% CI: 1.03-9.60 and 2.82-45.9, respectively) for relapse in the multivariate Poisson model. PD synovitis and GS tenosynovitis may be useful to identify RA patients in risk of relapse after DMARD tapering.

Predictors of joint damage progression and stringent remission in patients with established rheumatoid arthritis in clinical remission.

To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses. In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission. Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission. ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.

Association between MRI findings and patient‐reported outcomes in patients with rheumatoid arthritis in clinical remission and at relapse

To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n=70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P<.01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P<.03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse. Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported physical impairment at remission and relapse. The amount of damage in the wrist/hand is associated with reduced hand function.

Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial.

To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ-SC) in patients with rheumatoid arthritis (RA) who are in clinical remission. RA patients with active disease and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single-arm treatment phase with 162 mg of TCZ-SC administered once weekly (TCZ-SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ-SC administered every 2 weeks (TCZ-SC 162 mg q2w) for 24 weeks (open-label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission. In total, 179 (45%) of 401 patients in the single-arm phase achieved clinical remission and were randomized to continue to receive TCZ-SC 162 mg qw (n = 89) or to switch to TCZ-SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ-SC 162 mg qw remained in clinical remission compared to patients who received TCZ-SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ-SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ-SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change -4.07 points [SD 1.29] versus -3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups. Increasing the dose interval of TCZ-SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half-dose of TCZ-SC, and therefore this strategy deserves further investigation.

Histologic and Transcriptional Evidence of Subclinical Synovial Inflammation in Patients With Rheumatoid Arthritis in Clinical Remission.

Patients with rheumatoid arthritis (RA) in clinical remission may have subclinical synovial inflammation. This study was undertaken to determine the proportion of patients with RA in remission or with low disease activity at the time of arthroplasty who had histologic or transcriptional evidence of synovitis, and to identify clinical features that distinguished patients as having subclinical synovitis. We compared Disease Activity Score in 28 joints (DAS28) to synovial histologic features in 135 patients with RA undergoing arthroplasty. We also compared DAS28 scores to RNA-Seq data in a subset of 35 patients. Fourteen percent of patients met DAS28 criteria for clinical remission (DAS28 <2.6), and another 15% met criteria for low disease activity (DAS28 <3.2). Histologic analysis of synovium revealed synovitis in 27% and 31% of samples from patients in remission and patients with low disease activity, respectively. Patients with low disease activity and synovitis also exhibited increased C-reactive protein (CRP) (P = 0.0006) and increased anti-cyclic citrullinated peptide (anti-CCP) antibody levels (P = 0.03) compared to patients without synovitis. Compared to patients with a "low inflammatory synovium" subtype, 183 genes were differentially expressed in the synovium of patients with subclinical synovitis. The majority of these genes (86%) were also differentially expressed in the synovium of patients with clinically active disease (DAS28 ≥3.2). Thirty-one percent of patients with low clinical disease activity exhibited histologic evidence of subclinical synovitis, which was associated with increased CRP and anti-CCP levels. Our findings suggest that synovial gene expression signatures of clinical synovitis are present in patients with subclinical synovitis.

Superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis in clinical remission

The utility of superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis (RA) in clinical remission is unreported. This study aimed to compare SMI and power Doppler imaging (PDI) for the evaluation of hand joint lesions in these patients. Twenty-six patients with RA in clinical remission were enrolled. A total of 572 joints (52 wrist, 260 proximal interphalangeal, and 260 metacarpophalangeal joints) were detected by SMI and PDI. A semi-quantitative scale of 0–3 was used to compare the detection of synovial blood flow signal by SMI and PDI. Inter-observer agreement for the assessment of SMI and PDI scores was measured with kappa values. In the ten healthy volunteers, SMI and PDI signals were both scored 0. In the 26 RA patients, the remission rate via PDI was 65.4% but was only 42.3% via SMI. SMI also detected microvessel flow signal in seven patients diagnosed with clinical remission via PDI. Moreover, a total of 106 blood flow signals (18.5%) were detected by SMI, while 50 blood flow signals (8.7%) were detected by PDI. Compared with PDI, SMI increased 18.0% of power flow signals from Grade 0–1 and increased 13.7% of power flow signals from Grade 1–2. One joint classified as Grade 1 by PDI was classified as Grade 0 by SMI. Inter-observer agreement for PDI and SMI semi-quantitative scoring was moderate (kappa = 0.463). SMI seems more sensitive than PDI for detecting hand joint lesions in RA in clinical remission PDI, and could aid the achievement of true remission in RA patients.

The Value of Power Doppler Ultrasound in Patients With Rheumatoid Arthritis in Clinical Remission: Reclassifying Disease Activity?

ObjectivesThe aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. Material and methodsWe included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. ResultsEighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. ConclusionsAlthough around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28.

Patients with juvenile idiopathic arthritis in clinical remission with positive power Doppler signal in joint ultrasonography have an increased rate of clinical flare: a prospective study

BackgroundUltrasonography (US) studies carried out on joints of juvenile idiopathic arthritis (JIA) patients in clinical remission demonstrate the presence of subclinical synovitis. The significance of subclinical synovitis and the positive power Doppler (PD) signal on US in JIA in clinical remission is not well understood. The objectives of this study were to assess whether the changes detected by US in patients with JIA in clinical remission can predict disease flare and to evaluate factors associated with flare and joint damage over 30 months of follow-up.MethodsA prospective study was performed with clinical and ultrasound evaluation in 34 joints of JIA patients in clinical remission. Clinical evaluation including physical exam, functional capacity and inflammatory markers was performed at baseline and every six months thereafter, for a total period of 30 months. US evaluation included presence of synovitis, PD signal and erosion at baseline and every 12 months thereafter. Subclinical synovitis was defined when there was synovitis with or without positive PD signal in US joints of patients in clinical remission. Flare was defined as any joint presenting clinical arthritis requiring therapy modification.ResultsWe evaluated a total of 35 patients, 28 (80%) girls, 14 (40%) persistent oligoarticular subtype, 12 (34.3%) oligoarticular extended and 9 (25.7%) polyarticular and 26 (74.3%) in remission on medication. Twenty (57.1%) patients flared. The risk of flare was five times higher in patients with positive PD signal and 14 times higher in patients in remission on medication. Regarding the assessment of joints after 6 months and 12 months of US evaluation, 70/3162 (2.2%) joints and 80/2108 (3.8%) joints flared, respectively. Joints with subclinical synovitis with positive PD signal flared more after 6 and 12 months. Twenty five of 2108 (1.2%) joints showed erosion over time. Joints with subclinical synovitis with or without positive PD signal showed more erosion.ConclusionsPatients in remission on medication with subclinical synovitis with positive PD signal on US have a higher risk of flare, therefore they should be monitored closely during treatment. In the same way, joints with subclinical synovitis with or without positive PD signal should be monitored due to the risk of flare and joint damage.

Persistence of Disease-Associated Anti-Citrullinated Protein Antibody-Expressing Memory B Cells in Rheumatoid Arthritis in Clinical Remission.

In rheumatoid arthritis (RA), autoreactive B cells are pathogenic drivers and sources of anti-citrullinated protein antibodies (ACPAs) that are a diagnostic biomarker and predictor of worse long-term prognosis. Yet, the immunobiologic significance of persistent ACPA production at the cellular level is poorly understood. This study was undertaken to investigate the representation of ACPA-expressing switched-memory B cells in RA. In a cross-sectional study of RA patients, we investigated the presence of continued defects in immune homeostasis as a function of disease activity. Using an enzyme-linked immunosorbent assay (ELISA) and a sensitive multiplex bead-based immunoassay, we characterized fine binding antibody specificities in sera, synovial fluid (SF), and B cell culture supernatants. In this manner, we determined the frequency and epitope reactivity patterns of ACPAs produced by SF B cells and switched-memory blood B cells and compared the latter to serum ACPA levels and disease activity scores. Cultured B cells from SF were shown to spontaneously secrete ACPAs, while constitutive IgG autoantibody production by peripheral blood mononuclear cells (PBMCs) was substantially less frequent. After in vitro stimulation, PBMCs secreted IgG ACPA that was overwhelmingly from switched-memory B cells, across all patient groups treated with methotrexate and/or a tumor necrosis factor inhibitor. Intriguingly, the frequencies of ACPA-expressing switched-memory B cells significantly correlated with serum IgG anti-cyclic citrullinated peptide 3 (r = 0.57, P = 0.003). Moreover, treatment-induced clinical remission had little or no effect on the circulating burden of switched-memory ACPA-expressing B cells, in part explaining the continued dysregulation of humoral immunity. Our findings rationalize why therapeutic cessation most often results in disease reactivation and clinical flare. Hence, a clinical disease activity score is not a reliable indicator of the resolution of pathologic recirculating B cell autoimmunity.

Utility of Power Doppler Ultrasound-detected Synovitis for the Prediction of Short-term Flare in Psoriatic Patients with Arthritis in Clinical Remission.

Power Doppler ultrasound (PDUS) has been shown to detect subclinical synovitis in psoriatic arthritis (PsA), but its value is not yet fully understood. The aim of this study was to evaluate PDUS features at joint level in patients with PsA in clinical remission and to investigate its value for predicting short-term flares. Consecutive patients with PsA in clinical remission according to the attending rheumatologist and who fulfill minimal disease activity criteria and/or 28-joint Disease Activity Score in remission criteria underwent PDUS examination of 18 joints. All patients were followed up for 6 months. Disease flare was defined as any increase of disease activity generating the need of any of the following changes in therapy with disease-modifying antirheumatic drugs (DMARD) by the attending rheumatologist: dose increase, switch or addition of a different DMARD, and/or switch or addition of biological therapies. Among 54 patients with PsA in clinical remission, 15 (27.8%) experienced a flare within the next 6 months. Twenty patients had at least 1 joint with PDUS synovitis at baseline, and 13 (65%) of these had a disease flare during the followup period compared with only 2 of the 34 patients (5.9%) without baseline PDUS synovitis (relative risk = 11, 95% CI 2.8-44, p < 0.001). On logistic regression analysis, the only variables associated with short-term flares were baseline PDUS synovitis and the use of nonbiologic DMARD. Among patients with PsA in clinical remission, PDUS-detected synovitis was a strong predictor of short-term flare of the disease.

Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission.

ObjectiveClinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation.MethodsSeventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0–1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves.ResultsThe total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58–67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity.ConclusionThe present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.

Ultrasound-detected tenosynovitis independently associates with patient-reported flare in patients with rheumatoid arthritis in clinical remission: results from the observational study STARTER of the Italian Society for Rheumatology.

This study aimed to estimate the prevalence of US-detected tenosynovitis in RA patients in clinical remission and to explore its clinical correlates. A total of 427 RA patients in clinical remission were consecutively enrolled from 25 Italian rheumatology centres. Tenosynovitis and synovitis were scored by US grey scale (GS) and power Doppler (PD) semi-quantitative scoring systems at wrist and hand joints. Complete clinical assessment was performed by rheumatologists blinded to the US results. A flare questionnaire was used to assess unstable remission (primary outcome), HAQ for functional disability and radiographic erosions for damage (secondary outcomes). Cross-sectional relationships between the presence of each US finding and outcome variables are presented as odds ratios (ORs) and 95% CIs, both crude and adjusted for pre-specified confounders. The prevalence of tenosynovitis in clinical remission was 52.5% (95% CI 0.48, 0.57) for GS and 22.7% (95% CI 0.19, 0.27) for PD, while the prevalence of synovitis was 71.6% (95% CI 0.67, 0.76) for GS and 42% (95% CI 0.37, 0.47) for PD. Among clinical correlates, PD tenosynovitis associated with lower remission duration and morning stiffness while PD synovitis did not. Only PD tenosynovitis showed a significant association with the flare questionnaire [OR 1.95 (95% CI 1.17, 3.26)]. No cross-sectional associations were found with the HAQ. The presence of radiographic erosions associated with GS and PD synovitis but not with tenosynovitis. US-detected tenosynovitis is a frequent finding in RA patients in clinical remission and associates with unstable remission.

Active Tenosynovitis of the Palmar Flexor Tendon in Psoriatic Arthritis in Clinical Remission

La artritis reumatoide (AR) es la más frecuente de las enfermedades reumáticas inflamatorias crónicas. Al igual que muchas enfermedades autoinmunitarias es multifactorial, es decir, involucra factores ambientales, genéticos, inmunológicos, psicológicos y endocrinos. El diagnóstico de AR puede ser difícil de establecer. Se basa en la confrontación entre manifestaciones clínicas y pruebas de laboratorio (autoanticuerpos, parámetros biológicos de inflamación). El American College of Rheumatology (ACR) y la Liga Europea Contra el Reumatismo (EULAR) han revisado recientemente los criterios de clasificación. La AR es la enfermedad crónica sobre la cual se han efectuado los avances más considerables en los últimos años, ya sea en el campo de la fisiopatología, del diagnóstico o de los tratamientos. Esto ha permitido mejorar mucho el tratamiento y el pronóstico, hasta el punto de que la AR se considera hoy una patología menos grave: remisiones clínicas más frecuentes, menor discapacidad, menor destrucción articular, menos cirugías ortopédicas paliativas y mejor calidad de vida. El objetivo terapéutico que goza de consenso unánime es obtener la remisión clínica o, en su defecto, un bajo nivel de actividad con el propósito de prevenir las complicaciones a medio y largo plazo: destrucción articular, discapacidad funcional y complicaciones sistémicas, sobre todo cardiovasculares, pulmonares, metabólicas u óseas. Para alcanzar este objetivo, en la práctica corriente deben aplicarse los principios siguientes: diagnóstico precoz para instaurar un tratamiento precoz y control estricto de éste para fijar lo antes posible la estrategia adecuada. Las manifestaciones graves, que en la década de 1990 eran frecuentes, siguen presentes pero de forma más esporádica. La detección y el tratamiento de las comorbilidades de la AR se consideran un problema mayor, al igual que en cualquier enfermedad crónica (diabetes, cardiopatías, insuficiencia respiratoria, etc.).

Periodontal pathogens participate in synovitis in patients with rheumatoid arthritis in clinical remission: a retrospective case-control study.

The objective of this study was to investigate the role of periodontal pathogens in RA in remission. Twenty-one patients with active RA and 70 patients in clinical remission, including 48 patients with synovitis [US power Doppler (USPD)(+) group] and 22 patients without synovitis [USPD(-) group] were clinically assessed by US. CRP, ESR, haemoglobin, MMP-3, RF and ACPA were measured. Antibody titres against four types of periodontal pathogen [Aggregatibacter actinomycetemcomitans, Eikenella corrodens (Ec), Porphyromonas gingivalis and Prevotella intermedia (Pi)] were analysed using ELISA. Musculoskeletal US examination showed that 68.6% of patients with RA in clinical remission exhibited synovitis. CRP, ESR, haemoglobin, MMP-3 and RF levels in both the USPD(+) and USPD(-) groups were clearly lower compared with the RA group in non-remission. The IgG serum antibody titre against Ec in the non-remission RA(+) group was significantly greater than that in the USPD(+) group, and the IgG antibody titre against Pi in the non-remission RA and USPD(+) groups was greater than in the USPD(-) group. More than half of RA patients in remission showed persistent synovitis. This synovitis may be associated with periodontal disease-causing Pi. Thus, treating periodontal disease should also be considered in order to achieve more profound remission of RA.

Antibodies to infliximab and adalimumab in patients with rheumatoid arthritis in clinical remission: a cross-sectional study.

Objective. To investigate if antibodies towards biological TNF-α inhibitors (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in clinical remission and to relate any anti-TNFi Abs to circulating level of TNF-α inhibitor (TNFi). Methods. Patients with RA, treated with infliximab or adalimumab, and in clinical remission (DAS28(CRP) < 2.6) were included from 6 out-patient clinics. In blood samples, presence of anti-TNFi Abs was determined by radioimmunoassay, and concentration of bioactive TNFi was measured by a cell-based reporter gene assay. Results. Anti-TNFi Abs were present in 8/44 patients (18%) treated with infliximab and 1/49 patients (2%) treated with adalimumab (p = 0.012). In the former group, anti-TNFi Abs corresponded with low levels of TNFi (p = 0.048). Anti-TNFi Ab-positive patients had shorter disease duration at initiation of TNFi therapy (p = 0.023) but were similar for the rest of the compared parameters. Conclusions. In RA patients in clinical remission, anti-TNFi Abs occur frequently in patients treated with infliximab, while they occur rarely in patients treated with adalimumab. Presence of anti-infliximab Abs is accompanied by low or undetectable levels of infliximab. These data suggest that continued infliximab treatment may be redundant in a proportion of RA patients treated with infliximab and in clinical remission.