Early Rheumatoid Arthritis Patients Research Articles

Treatment strategies are more important than drugs in the management of rheumatoid arthritis.

The treatment of inflammatory arthritides has been changed dramatically in the past two decades with the introduction of the biological (b) disease-modifying anti-rheumatic drugs (DMARDs) as well as the targeting synthetic (ts) DMARDs that can be used as monotherapy or in combination with conventional synthetic (cs) DMARDs. The concept of treat to target (T2T) and tight control monitoring of disease activity represents a therapeutic paradigm of modern rheumatology. In rheumatoid arthritis (RA), this treatment approach has proven to be effective in many clinical trials and is now a well-established approach. The most common treatment strategies rely on the combination of csDMARDs (mainly methotrexate, sulfasalazine and hydroxychloroquine). This comes from different studies which compare the outcomes of combination therapies versus csDMARD monotherapy or versus methotrexate plus biologics in early RA patients. Here, we review the literature of the most important T2T studies for RA patients. The results showed that a tight control strategy appears to be more important than a specific drug to control RA. T2T approach aiming for remission or low disease activity can be achieved in early RA patients using less expensive drugs in comparison to newer drugs and this may need to be recognised in the future recommendations for the management of RA. KEY POINTS: • Tight-control and treat-to-target (T2T) strategies are the cornerstone in achieving remission or low disease activity in rheumatoid arthritis (RA) • A plethora of clinical trials has confirmed the efficacy of csDMARDs when the tight-control and T2T strategies are applied • T2T and tight-control strategies are a less expensive option in comparison to newer drugs and may be recognised in the future recommendations for the management of RA. • Treatment decisions and strategies are more important than just the drugs.

Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis.

To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy. A total of 230 DMARD-naïve early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms. MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40]. Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA. Clinicaltrials.gov, http://clinicaltrials.gov, NCT01205854.

Factors associated with successful discontinuation of certolizumab pegol in early rheumatoid arthritis.

AimThe Certolizumab–Optimal Prevention of joint damage for Early Rheumatoid Arthritis (C‐OPERA) study demonstrated that in methotrexate (MTX)‐naïve early RA patients with poor prognostic factors, 1‐year certolizumab pegol (CZP) therapy added to the first year of 2‐year optimized MTX therapy brings radiographic and clinical benefits through 2 years even after stopping CZP. This exploratory analysis aimed to identify factors at baseline and at CZP discontinuation associated with successful CZP discontinuation.MethodsMTX‐naïve early RA patients with poor prognostic factors entered C‐OPERA (NCT01451203), a multicenter, randomized controlled trial. Patients were randomized to CZP + MTX (n = 159) or PBO + MTX (n = 157); those who completed the 1‐year, double‐blind period received MTX alone in Year 2 (CZP + MTX→MTX, n = 108; PBO + MTX→MTX, n = 71). Association between factors at baseline or at discontinuation of CZP and clinical/radiographic outcomes were evaluated by multiple logistic regression analysis. Predictive value cut‐offs were calculated using receiver operating characteristic analysis.ResultsSex (male) and low baseline Disease Activity Score of 28 joints – erythrocyte sedimentation rate (DAS28‐ESR) were associated with simple disease activity index (SDAI) remission (≤3.3), whereas high baseline DAS28‐ESR and modified total Sharp score (mTSS) were associated with clinically relevant radiographic progression (yearly progression mTSS > 3) at Week 104 (across both treatment arms). Low DAS28‐ESR (<2.1) and rheumatoid factor (RF; <74 IU/mL) at discontinuation of CZP were associated with SDAI remission at Week 104. At Week 104, SDAI remission was achieved by 75.0% (42/56) of patients with low DAS28‐ESR and RF at discontinuation, compared to 15.4% (2/13) of patients with high DAS28‐ESR and RF.ConclusionPatients with low RF and low disease activity after treatment with CZP + MTX may be able to discontinue CZP without risk of loss of response.

Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthritis.

BackgroundT‐cell activation pathways have been proposed as trigger mechanisms in the pathogenesis of rheumatoid arthritis (RA). CD28 and CTLA‐4 play major roles in regulating the stimulatory and inhibitory co‐signals in T cells.ObjectiveTo analyze the association between soluble and surface expression of CD28 and CTLA‐4 with the clinical parameters of RA patients.MethodsA total of 35 RA patients classified as early RA (n = 14), chronic RA (n = 14), and untreated RA (n = 7), as well as 7 age‐ and sex‐matched control subjects (CS) were included. Surface expression of CD28 and CTLA‐4 on T cells was evaluated by flow cytometry. Soluble levels of CD28 (sCD28), CTLA‐4 (sCTLA‐4), and anti‐CCP antibodies were measured by ELISA.ResultsA significant lower percentage of CD8 + T cells positive to CD28 (CS = 64.9% vs RA = 42.7%, P = .04), and diminished surface expression of CD28 (CS: MFI = 122.9 vs RA: MFI = 33.1, P = .006), were found in chronic RA patients compared to CS. Higher sCD28 were observed in early RA patients compared with chronic RA patients (P < .05). sCTLA‐4 was found increased in untreated RA patients compared to early RA patients (P < .05). sCD28 concentration correlated with anti‐CCP levels (rho = −0.12; P = .032). The soluble and surface expressions of CTLA‐4 were not associated with RA clinical parameters.ConclusionsIn RA, the percentage of CD8 + CD28+ T cells decreases and expresses fewer membrane CD28 than CS. sCD28 levels are lower in chronic RA and are associated negatively with anti‐CCP levels. sCTLA 4 levels are lower in early RA patients than in untreated RA patients.

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

BackgroundSerum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls.MethodsIn order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC–MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90).ResultsWe observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters.ConclusionsThis study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

Effectiveness and safety over 3 years after the 2-year U-Act-Early trial of the strategies initiating tocilizumab and/or methotrexate.

ObjectivesU-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice.MethodsAt the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage.ResultsOf patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P > 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups.ConclusionAlthough in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = − 0.4, p = 0.009) and between vWF:Ag and TH2 (R = − 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Diagnostic value of anti-fibrinogen citrullinated peptide in rheumatoid arthritis

ObjectiveTo determinate the diagnostic value of an antibody against a citrullinated fibrinogen peptide in Cuban patients with rheumatoid arthritis, using an enzyme immunoassay. Materials and methodsA citrullinated peptide of fibrinogen designed by informatics prediction was synthesised and used in an enzyme immunoassay. The participants were 81 patients with early disease, 81 patients with established disease, 58 patients with other rheumatic and inflammatory diseases, and 43 healthy individuals. Anti-citrullinated fibrinogen peptide, anti-mutated citrullinated vimentin, anti second generation citrullinated peptides and rheumatoid factor antibodies were determined by enzyme-linked immunosorbent assay. ResultsDetermination of anti-citrullinated peptide of fibrinogen antibodies by the designed enzyme immunoassay showed the best diagnostic value in early rheumatoid arthritis patients, with the highest value sensitivity (84%), negative predictive value (85%), Youden index (0.73%) and area under the receiver operating curve (0.9192). Specificity (89%) and positive predictive value (88%) were higher than rheumatoid factor, similar to anti-mutated citrullinated vimentin, but lower than second generation anti-citrullinated peptides assay. The positivity of C-reactive protein was associated with the presence of anti-citrullinated fibrinogen peptide antibodies and the titres of these antibodies correlated with clinical activity in early disease. ConclusionsThe immunoassay designed with a citrullinated fibrinogen peptide has a high diagnostic value and can identify patients with greater clinical activity in early rheumatoid arthritis.

Association Between Vitamin D Deficiency and Disease Activity, Disability, and Radiographic Progression in Early Rheumatoid Arthritis: The ESPOIR Cohort.

To evaluate the association of baseline serum level of vitamin D with disease activity, disability, and radiographic damage over the first year in early rheumatoid arthritis (RA). Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and van der Heijde modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitamin D level and radiographic progression (mTSS increased by ≥ 1 point) or disability (HAQ-DI ≥ 0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes. Among 813 patients with early arthritis, data for 645 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10-29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency compared with groups 2 and 3 combined (P = 0.007 and P = 0.001, respectively), as was mean mTSS, but not significantly (p = 0.076). On multivariate analysis, baseline vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76). Vitamin D deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients. [ClinicalTrials.gov: NCT03666091].

Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients.

To identify serum sphingolipids that could act as candidate biomarkers in RA. We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids). Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses. We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.

The value of MRI examination on bilateral hands including proximal interphalangeal joints for disease assessment in patients with early rheumatoid arthritis: a cross-sectional cohort study

BackgroundBilateral hands including proximal interphalangeal joints (PIPJs) are recommended on physical, X-ray radiographic, or ultrasonographic examination by clinical guidelines of rheumatoid arthritis (RA), but MRI still tends to examine unilateral wrists and/or MCPJs. We aimed to demonstrate the advantages of MRI examination on bilateral hands including PIPJs for disease assessment in early RA patients.MethodsActive early RA patients received 3.0T whole-body MRI examination with contrast-enhanced imaging on bilateral wrists, MCPJs, and PIPJs. MRI features were scored referring to the updated RAMRIS. Clinical assessments were conducted on the day of MRI examination.ResultsThe mean time of MRI examination was 24 ± 3 min. MRI bone erosion in MCPJs would be missed-diagnosed in 23% of patients if non-dominant MCPJs were scanned unilaterally, while osteitis in MCPJs would be missed-diagnosed in 16% of patients if dominant MCPJs were scanned unilaterally. MRI synovitis severity was also asymmetric: 21% of patients showing severe synovitis unilaterally in non-dominant MCPJs/PIPJs and other 20% showing severe synovitis unilaterally in dominant MCPJs/PIPJs. Among these early RA patients, MRI tenosynovitis occurred the most frequently in wrist extensor compartment I, while MRI examination on bilateral hands demonstrated no overuse influence present. However, overuse should be considered in dominant PIPJ2, PIPJ4, and IPJ of thumb of which MRI tenosynovitis prevalence was respectively 18%, 17%, or 16% higher than the non-dominant counterparts. Early MRI abnormality of nervus medianus secondary to severe tenosynovitis occurred either in dominant or non-dominant wrists; MRI of unilateral hands would take a risk of missed-diagnosis. Common MRI findings in PIPJs were synovitis and tenosynovitis, respectively in 87% and 69% of patients. MRI tenosynovitis prevalence in IPJ of thumb or PIPJ5 was much higher than the continued wrist flexor compartments. MRI synovitis or tenosynovitis in PIPJs independently increased more than twice probability of joint tenderness (OR = 2.09 or 2.83, both p < 0.001).ConclusionsIn consideration of asymmetric MRI features in early RA, potential overuse influence for certain tenosynovitis in dominant hands, and high prevalence of MRI findings in PIPJs, MRI examination on bilateral hands including PIPJs is deserved for disease assessment in early RA patients.

Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis

BackgroundAntibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses.MethodsA case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks.ResultsThere was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls.ConclusionsWe confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression.

Long-term outcomes of patients who rate symptoms of rheumatoid arthritis as 'satisfactory'.

ObjectivesTo describe outcomes of patients with early RA in a patient acceptable symptom state (PASS) at treatment initiation and to identify clusters of symptoms associated with poor outcomes.MethodsData came from the Rheumatoid Arthritis Medication Study, a UK multicentre cohort study of RA patients starting MTX. The HAQ, DAS28 and other patient-reported outcome measures (PROMs) were collected at baseline, and at 6 and 12 months. Patients answering yes to the question ‘Is your current condition satisfactory, when you take your general functioning and your current pain into consideration?’ were defined as PASS; patients answering no were defined as N-PASS. Symptom clusters in the baseline PASS group were identified using K-medians cluster analysis. Outcomes of baseline PASS vs N-PASS patients and each cluster are compared using random effects models.ResultsOf 1127 patients, 572 (50.8%) reported being in PASS at baseline. Over one year, baseline PASS patients had lower DAS28 (mean difference = −0.71, 95% CI −0.83, −0.59) and HAQ scores (mean difference = −0.48, 95% CI −0.56, −0.41) compared with N-PASS patients. Within the baseline PASS group, we identified six symptom clusters. Clusters characterized by high disease activity and high PROMs, or moderate disease activity and high PROMs, had the worst outcomes compared with the other clusters.ConclusionDespite reporting their condition as ‘satisfactory’, early RA patients with high PROM scores are less likely to respond to therapy. This group may require increased vigilance to optimize outcomes.

An updated matrix to predict rapid radiographic progression of early rheumatoid arthritis patients: pooled analyses from several databases.

In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.

Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

BackgroundThe aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset < 1 year) treated according to treat-to-target (T2T) therapy.MethodsBaseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined.ResultsA subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P < 0.05) and 3-year follow-up (r = 0.21, P < 0.05). Individual slopes of the relationship between DAS28-ESR and progression scores in each time interval were significantly correlated over time and the slope of the first 6 months was moderately associated with this slope at later time points (r between 0.39 and 0.59; P values < 0.001). Between 15.9 to 22.7% and 16.7 to 38.5% of patients with low and moderate time-integrated disease activity, respectively, experienced relevant (ΔSHS ≥ 3) radiographic progression at the different time intervals. Analyses using CRP showed similar results.ConclusionsIn early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years.Trial registrationNetherlands Trial Register NTR578, 12 January 2006.

Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional Study.

Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC-lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects—ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9–5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1–3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3–8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I. 1.002–1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002–1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96–0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4–9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24–4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment.

Do DMARDs and biologic agents protect from cardiovascular disease in patients with inflammatory arthropathies?

Treat-to-target (T2T) is currently the most fashionable strategy for treatment-naïve, early rheumatoid arthritis (RA) patients. A T2T approach can lead to a complete and drug-free disease remission, whereas failure to obtain remission leads to damage early in the disease course. Hence, one should try to achieve high remission rates as early as possible, implementing the best therapeutic strategies available. Methotrexate (MTX) combined with glucocorticoid bridging is the mainstay of T2T. However, MTX is often used suboptimally in RA patients for many reasons, including poor tolerability, low compliance, and safety issues. Recent evidence has suggested that novel targeted synthetic DMARDs (tsDMARDs) such as the Janus-kinase (JAK) inhibitors in combination with glucocorticoids yielded better outcomes in early RA than conventional treatment. Such an approach may have advantages in terms of patients' outcomes, though some concerns about serious adverse events need to be addressed.

Palindromic Rheumatism Frequently Precedes Early Rheumatoid Arthritis: Results From an Incident Cohort.

BackgroundThis multicenter incident cohort aimed to characterize how often early rheumatoid arthritis (ERA) patients self‐report episodic joint inflammation (palindromic rheumatism) preceding ERA diagnosis and which characteristics differentiate these patients from those without prior episodic symptoms.MethodsData were from patients with early confirmed or suspected RA (more than 6 weeks and less than 12 months) enrolled in the Canadian Early ArThritis CoHort (CATCH) between April 2017 to March 2018 who completed study case report forms assessing joint pain and swelling prior to ERA diagnosis. Chi‐square and t tests were used to compare characteristics of patients with and without self‐reported episodic joint inflammation prior to ERA diagnosis. Multivariable logistic regression was used to identify sociodemographic and clinical measures associated with past episodic joint inflammation around the time of ERA diagnosis.ResultsA total of 154 ERA patients were included; 66% were female, and mean (SD) age and RA symptom duration were 54 (15) years and 141 (118) days. Sixty‐five (42%) ERA patients reported a history of episodic joint pain and swelling, half of whom reported that these symptoms preceded ERA diagnosis by over 6 months. ERA patients with past episodic joint inflammation were more often female, had higher income, were seropositive, had more comorbidities, fewer swollen joints, and lower Clinical Disease Activity Index (CDAI) around the time of ERA diagnosis (P < 0.05). These associations remained significant in multivariable regression adjusting for other sociodemographic and RA clinical measures.ConclusionAlmost half of ERA patients experienced episodic joint inflammation prior to ERA diagnosis. These patients were more often female, had higher income, and presented with milder disease activity at ERA diagnosis.

Increased plasticity of non-classic Th1 cells toward the Th17 phenotype

Objectives: To analyze occurrence and plasticity of two recently described distinct subtypes of Th1 cells named classic (CD161−/CCR6−) and non-classic (CD161+/CCR6+) Th1 cells in early rheumatoid arthritis (RA) patients and healthy controls (HCs).Methods: Frequencies of in vivo-generated Th1 cell populations were assessed after cytokine secretion assay for IFNγ/IL-17 and surface staining for CD161/CCR6. Viable Th1 cells (IFNγ+IL-17−) were sorted into classic Th1 (CD161-CCR6−) and non-classic Th1 (CD161+CCR6+) cells, trans-differentiated under different Th cell-inducing conditions, and assessed for plastic changes by analyzing the Th cell-associated cytokine and transcription factor profiles.Results: Ex vivo frequencies of classic (CD161−CCR6−) and non-classic (CD161+CCR6+) Th1 cells as well as related Th1 cell subpopulations CD161+CCR6− and CD161−/CCR6+ did not differ significantly between RA and HCs. However, trans-differentiation of ex vivo non-classic (CD161+CCR6+) and CD161−/CCR6+ Th1 cells resulted in a substantial shift toward Th17 and Th1/Th17 phenotypes, particularly under Th17-inducing conditions. In contrast, classic (CD161−/CCR6−) and CD161+CCR6− Th1 cells showed higher plasticity towards IL-4-producing cells, most of them shifting to a Th1/Th2 phenotype.Conclusion: Whereas non-classic (CD161+/CCR6+) and CD161-CCR6+ Th1 cells demonstrated an increased plasticity towards IL-17- phenotypes, classic Th1 and CD161+CCR6− Th1 cells showed more plasticity towards IL-4-producing phenotypes.

Efficacy and safety of combined therapy with synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: Systematic literature review

Objective(1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) and (2) to design practical recommendations on their use. MethodsA systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomised clinical trials that analysed the efficacy and/or safety of (1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA and (2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. ResultsUltimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a “treat to target” strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. ConclusionsThese recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA.