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Objectives To evaluate the safety of treatment strategies in patients with early RA. Methods Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using meta-analysis and network meta-analysis (NMA). Results From an initial search of 3423 studies, 20 were included, involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient-years for serious adverse events were 69.8 (95% CI: 64.9, 74.8), serious infections 18.9 (95% CI: 16.2, 21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5, 1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47, 7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02, 1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates. Conclusion The study revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful. [ABSTRACT FROM AUTHOR]

Objective The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. Methods Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells. Results As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. Conclusion An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months. [ABSTRACT FROM AUTHOR]

Objective 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. Methods 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. Results 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). Conclusion 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. [ABSTRACT FROM AUTHOR]

Objectives The use of MR-imaging is recommended for the early detection of RA. Next to the small joints of the hands, foot-joints are often involved. Therefore, imaging inflammation of the feet in addition to hands may be informative, but prolongs scan-time and leads to additional costs. We studied the value of MRI of the feet alone and complementary to MRI of the hands in patients with clinically suspect arthralgia (CSA). Methods 357 consecutively included CSA patients underwent contrast-enhanced 1.5 T-MRI of hand (MCP2-5 and wrist) and foot (MTP1-5) joints at baseline. Scans were scored for synovitis, osteitis and tenosynovitis. After ⩾1 year follow-up, the development of clinically apparent inflammatory arthritis (IA) was studied. Cox regression was performed and test characteristics were evaluated. Sensitivity analyses were performed for the outcome RA-development (2010-criteria). Results MRI-detected tenosynovitis of the feet was associated with IA-development, independently from synovitis and osteitis hazard ratio (HR) (95%CI) 4.75 (2.38; 9.49), and independently from ACPA and CRP, HR 3.13 (1.48; 6.64). From all CSA patients, 11% had inflammation in hands and feet, 29% only in hands and 3% only in feet. In line with this finding, the addition of MRI-feet to MRI-hands did not increase the predictive accuracy; the sensitivity remained 77%, while the specificity decreased from 66% to 62%. Sensitivity analyses with RA development as outcome showed similar results. Conclusion Tenosynovitis at the forefeet in CSA predicted IA and RA development. Addition of foot MRI to hand MRI did not increase the accuracy. Foot MRI can be omitted to reduce scan time and costs and increase the feasibility. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether MTX should be combined with an additional DMARD and bridging glucocorticoids as initial treatment for patients with early RA to induce an effective long-term response. Methods The Care in early RA study is a two-year investigator-initiated pragmatic multicentre randomized trial. Early RA patients, naïve to DMARDs and glucocorticoids, were stratified based on prognostic factors. High-risk patients were randomized to COBRA-Classic (n = 98): MTX, sulfasalazine, prednisone step-down from 60 mg; COBRA-Slim (n = 98): MTX, prednisone step-down from 30 mg; or COBRA-Avant-Garde (n = 93): MTX, leflunomide, prednisone step-down from 30 mg. Low-risk patients were randomized to COBRA-Slim (n = 43); or Tight Step Up (TSU) (n = 47): MTX without prednisone. Clinical/radiological outcomes at year 2, sustainability of response, safety and treatment adaptations were assessed. Results In the high-risk group 71/98 (72%) patients achieved a DAS28-CRP < 2.6 with COBRA-Slim compared with 64/98 (65%) with COBRA-Classic and 69/93 (74%) with COBRA-Avant-Garde (P = 1.00). Other clinical/radiological outcomes and sustainability of response were similar. COBRA-Slim treatment resulted in less therapy-related adverse events compared with COBRA-Classic (P = 0.02) or COBRA-Avant-Garde (P = 0.005). In the low-risk group, 29/43 (67%) patients on COBRA-Slim and 34/47 (72%) on TSU achieved a DAS28-CRP < 2.6 (P = 1.00). On COBRA-Slim, low-risk patients had lower longitudinal DAS28-CRP scores over 2 years, a lower need for glucocorticoid injections and a comparable safety profile compared with TSU. Conclusion All regimens combining DMARDs with glucocorticoids were effective for patients with early RA up to 2 years. The COBRA-Slim regimen, MTX monotherapy with glucocorticoid bridging, provided the best balance between efficacy and safety, irrespective of patients' prognosis. Trial registration ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01172639. [ABSTRACT FROM AUTHOR]

Objectives : The aim was to assess of the morphology, intensity, and activity of changes in the first ultrasonographic (US) examination of hands and feet in patients with early arthritis (lasting up to 12 months) who were ultimately diagnosed with rheumatoid arthritis (RA). An attempt was made to demonstrate a correlation between the intensity of lesions in US and selected laboratory parameters. Material and methods : Ultrasonographic examination was performed using a LOGIC GE 500 device on a group of 60 patients with arthritis (46 women, 14 men) aged 18–80, previously untreated. In total, 3120 hand and feet joints were examined. The assessment focused on the presence of joint effusion, synovial proliferation and power Doppler signals (assessed on a semi-quantitative scale). Each patient underwent laboratory tests, necessary for making a diagnosis. In order to analyze the correlations between changes in US and laboratory parameters, erythrocyte sedimentation rate (ESR), reactive protein test (CRP), rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPAs) were used. Results : In the study group, the average duration of arthritis symptoms until the first US examination was 5.6 months. Among the 3120 examined hand and foot joints, deviations from the norm appeared in 1093 joints, synovial hypertrophy was found in 471 joints (grade 1 synovial hypertrophy was reported most frequently), while presence of signal in Power Doppler was revealed in 261 joints (grade 1 was observed most frequently). A statistically significant correlation was found between the intensity of changes in Power Doppler and CRP concentration. Conclusions : In patients with increased concentrations of CRP, we may expect arthritis of higher intensity, therefore, in order to prevent the progression of destructive changes, it is necessary to quickly implement effective disease-modifying antirheumatic treatment. The conducted research showed that the activity of joint inflammation is not affected by the values of ESR and the presence of RF or ACPAs.

The main aim of metabolomics is to make a comprehensive study of metabolites, the intermediates of biochemical processes in living organisms. Any pathophysiological mechanism caused by disease will inevitably lead to related changes in the concentrations of specific metabolites. In line with this, metabolomics offers a promising laboratory tool for the analysis of potential diagnostic biomarkers that may be used to assess susceptibility to a disease and to evaluate the prognosis and therapeutic response to treatment. Recent data have shown that metabolomics analysis in rheumatoid arthritis has made possible more efficient diagnosis, discrimination between patients with regard to disease activity, prediction of the response to a particular treatment approach, differentiation between rheumatic disease subtypes and greater understanding of the pathophysiology of this disease. Here we characterize metabolomics as a comprehensive laboratory tool and review its potential in the diagnosis, prognosis and treatment of rheumatic diseases such as rheumatoid arthritis.

Objectives To study prognostic factors for achievement of sustained remission in early RA patients receiving semi-personalized tight controlled treatment, and to assess the consistency of potential predictors across definitions of sustained remission. Methods DMARD-naïve early RA patients with symptom duration <2 years were treated according to a pre-defined algorithm within the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen trial. The algorithm allowed treatment adjustments based on established risk factors for a worse outcome. Multivariate logistic regression was used to examine baseline predictors of achieving sustained DAS remission at 16–24 months, and to assess predictors of secondary remission outcomes (all sustained 16–24 months): ACR/EULAR Boolean, Simplified Disease Activity Index (SDAI), no swollen joints and a composite outcome of DAS remission, no swollen joints and no radiographic progression. Results Of 222 patients, 118 (53%) reached sustained DAS remission, while 53 (24%) reached sustained ACR/EULAR Boolean and 73 (33%) sustained SDAI remission. More joint tenderness, assessed by Ritchie Articular Index, was a negative predictor of reaching sustained DAS remission (odds ratio (OR) = 0.90/U, 95% CI: 0.86, 0.94), sustained ACR/EULAR Boolean remission (OR = 0.92, 95% CI: 0.86, 0.98), sustained SDAI remission (OR = 0.94, 95% CI: 0.90, 1.00) as well as the two alternative definitions of sustained remission. Short symptom duration at baseline predicted sustained Boolean and SDAI remission. Other identified predictors were inconsistent across outcomes. Conclusion A higher tender joint score at baseline consistently reduced the chance of reaching sustained remission across all definitions. Our results support sustained remission as an achievable goal in early RA, especially when initiating DMARDs within 3 months symptom duration. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01205854 [ABSTRACT FROM AUTHOR]

Objectives. To examine associations between BMI and disease activity, functional ability and quality of life in RA. Methods. Data from two consecutive, similarly designed UK multicentre RA inception cohorts were used: the Early RA Study (ERAS) and the Early RA Network (ERAN). Recruitment figures/median follow-up for the ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years), respectively. Standard demographic and clinical variables were recorded at baseline and annually. Multilevel piecewise longitudinal models with a change point at 2 years were used with the 28-joint DAS (DAS28), ESR, HAQ and 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) components as dependent variables. BMI was examined in separate models as both continuous and categorical variables (based on World Health Organization definitions) and up to 5 years from disease onset. Results. BMI data from 2386 newly diagnosed RA patients (11 348 measures) showed an increase in BMI of 0.27 U annually (95% CI 0.21, 0.33). Baseline obesity was associated with a significant reduction in the odds of achieving a low year 2 DAS28 [OR 0.52 (95% CI 0.41, 0.650)]. At year 2, HAQ and SF-36 PCS scores were significantly worse but not at year 5 in patients obese at baseline. Obesity at year 2 was associated with higher DAS28 scores at year 2, but not at year 5, and also associated with significantly higher HAQ and SF-36 PCS scores at years 2 and 5. Conclusion. Obesity prevalence is rising in early RA and associates with worse disease activity, function and health-related quality of life, with a significant negative impact on achieving a low DAS28. The data argue strongly for obesity management to become central to treatment strategies in RA. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the effect of initiation of tocilizumab, with or without MTX, compared with MTX alone on patient-reported outcomes (PROs), in DMARD-naı ¨ve patients with early RA. Methods. In U-Act-Early, patients initiated treat-to-target step-up MTX, tocilizumab or tocilizumab plus MTX therapy. PROs assessed included the Functional Assessment of Chronic Illness Therapy-Fatigue, 36-item Short Form (SF-36), five dimensional EuroQol (EQ-5D) and the Revised Illness Perception Questionnaire. Differences between strategy groups over time and proportions of patients exceeding minimum clinically important differences (MCID) were evaluated. Results. During the 2-year study period, significant improvements were found in the tocilizumab strategies in the SF-36 physical component score (tocilizumab, P = 0.012; tocilizumab plus MTX, P = 0.044) and EQ-5D score (tocilizumab plus MTX, P = 0.020) when compared with the MTX strategy. No significant differences were noted in other PROs (P≥0.052, except for the domain 'identity' in the Illness Perception Questionnaire; tocilizumab vs MTX, P = 0.048). The proportions of patients achieving MCID in SF-36 physical component score were significantly higher at 12 and 52weeks (P≤0.049) in the tocilizumab arms when compared with the MTX arm. At week 24, the proportion achieving MCID in EQ-5D was significantly higher in the tocilizumab plus MTX arm vs the MTX arm (P = 0.045). Conclusion. Initiation of treat-to-target tocilizumab therapy resulted in significantly improved PROs, especially within the first 24weeks, when compared with initiation of MTX therapy. Also on the patients' level, initiating tocilizumab may be considered as a valuable strategy in DMARD-naı ¨ve patients with early RA. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01034137. [ABSTRACT FROM AUTHOR]

Objectives. To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. Methods. Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. Results. Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)]. Conclusion. HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment. [ABSTRACT FROM AUTHOR]

Objectives. To assess the diagnostic value of MRI for early RA. In some RA patients, a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence for its reliability is limited. Methods. MRI of hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic (229 presented with RA, 159 with other arthritides and 201 with UA). Symptom-free controls provided a reference for defining an abnormal MRI. In preliminary investigations, MRI of patients who presented with RA was compared with MRI of symptom-free controls and of patients with other arthritides. Thereafter, the value of MRI in early RA diagnosis was determined in UA patients using the 1-year follow-up on fulfilling the 1987 RA criteria and start of disease-modifying drugs as outcomes. Results. Preliminary investigations were promising. Of the UA patients, 14% developed RA and 37% started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA development independent of other types of MRI-detected inflammation [odds ratio (OR) = 7.5, 95% CI: 2.4, 23] and also independent of age and other inflammatory measures (swollen joints, CRP) (OR = 4.2, 95% CI: 1.4, 12.9). Within UA patients, the negative predictive value of abnormal tenosynovitis was 95% (95% CI: 89%, 98%) and the positive predictive value 25% (95% CI: 17%, 35%). The performance was best in the subgroup of UA patients presenting with oligoarthritis (18% developed RA): the positive predictive value was 36% (95% CI: 23%, 52%), the negative predictive value was 98% (95% CI: 88%, 100%), the sensitivity was 93% (95% CI: 70%, 99%) and the specificity was 63% (95% CI: 51%, 74%). Conclusion. MRI contributes to the identification of UA patients who will develop RA, mostly in UA patients presenting with oligoarthritis. [ABSTRACT FROM AUTHOR]

Objective. To assess the value of quantitative vascular imaging by power Doppler US (PDUS) as a tool that can be used to stratify patient risk of joint damage in early seropositive RA while still biologic naive but on synthetic DMARD treatment. Methods. Eighty-five patients with seropositive RA of <3 years duration had clinical, laboratory and imaging assessments at 0 and 12 months. Imaging assessments consisted of radiographs of the hands and feet, two-dimensional (2D) high-frequency and PDUS imaging of 10 MCP joints that were scored for erosions and vascularity and three-dimensional (3D) PDUS of MCP joints and wrists that were scored for vascularity. Results. Severe deterioration on radiographs and ultrasonography was seen in 45 and 28% of patients, respectively. The 3D power Doppler volume and 2D vascularity scores were the most useful US predictors of deterioration. These variables were modelled in two equations that estimate structural damage over 12 months. The equations had a sensitivity of 63.2% and specificity of 80.9% for predicting radiographic structural damage and a sensitivity of 54.2% and specificity of 96.7% for predicting structural damage on ultrasonography. Conclusion. In seropositive early RA, quantitative vascular imaging by PDUS has clinical utility in predicting which patients will derive benefit from early use of biologic therapy. [ABSTRACT FROM AUTHOR]

Objective. To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. Methods. Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. Results. Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. Conclusion. Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA. Key words: rheumatoid arthritis, therapy, outcome measures, disease activity scores, fibromyalgia, DMARDs, fibromyalgic RA, treat to target, early rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Objective. RA is a chronic disease with frequent psychological co-morbidities, of which depression and anxiety are two common manifestations. We aimed to identify predictive factors of psychological distress in a large prospective cohort of very early RA patients.Methods. ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) is a multicentre, longitudinal and prospective cohort study of patients with early arthritis (<6 months disease duration). The study sample comprised 641 patients with very early RA according to the 2010 ACR/European League Against Rheumatism RA criteria from the ESPOIR cohort. Psychological distress was assessed over 3 years by the five-item Mental Health Inventory questionnaire at various time points (baseline, 6, 12, 18, 24 and 36 months). Logistic regression with a generalized estimating equation model was used to analyse the association of disease variables and risk of psychological distress.Results. At baseline, 46.9% of RA patients were screened as positive for psychological distress. Over 3 years, psychological distress decreased significantly, with a prevalence of 25.8% at 36 months. The HAQ Disability Index (HAQ-DI) score was the most important factor predicting psychological distress over 3 years [odds ratio 2.10 (95% CI 1.41, 3.14)–3.59 (2.29, 5.63)]. Baseline biological and radiological variables and treatment regimens were not associated with distress.Conclusion. Psychological distress in very early RA is frequent and the HAQ-DI score is a predictor of depression and anxiety in these patients. A psychological evaluation in patients with early RA is important for further individual psychiatric diagnosis and management. [ABSTRACT FROM PUBLISHER]

Objective. The objective of this study was to determine the prevalence and distribution of bone erosions detectable by US in patients with early RA (ERA) in comparison with long-standing RA (LSRA), other erosive diseases and healthy controls.Methods. Thirty patients with ERA and 80 patients with LSRA were consecutively recruited. Thirty patients with PsA, 15 with primary OA, 10 with gout and 20 healthy subjects were included as controls. Bone erosions were investigated at the following anatomical sites: the second and fifth metacarpal heads, the ulnar head and the first and fifth metatarsal heads, bilaterally. Dorsal, volar and lateral aspects were explored on longitudinal and transverse views.Results. At least one US bone erosion was found in 20 (66.7%) of 30 patients with ERA and in 10 (33%) of them it was found on the fifth metatarsal head. Bone erosions were most frequently found on the lateral quadrants of all scanned anatomical sites. If the second and fifth metacarpal heads and the fifth metatarsal head were scanned, an erosive disease could be found in 60% of ERA patients. The first metatarsal head was most frequently involved in the disease control group.Conclusion. This study found a high percentage of ERA patients with US bone erosions, with the fifth metatarsal head and the lateral aspects the most frequently involved site and quadrants. US scanning for bone erosions on a few target joints was found feasible and provided information not obtainable with clinical examination. [ABSTRACT FROM PUBLISHER]

Objective. To assess the efficacy of LEF administered with or without a loading dose in DMARD-naïve patients with early RA. Methods. This multicentre, double-blind, randomized clinical trial included adults with RA diagnosed within 6 months (ACR criteria). Patients were randomly selected to receive either a 100 mg loading dose or a 20 mg fixed dose of LEF for 3 days, followed by a 3-month open-label maintenance period of 20 mg LEF qd. The primary outcome criterion was ACR20 response rate at study end in the intent-to-treat population. Secondary criteria were ACR20, ACR50, ACR70 and DAS28 response rates at 1 and 3 months and safety. Results. The intent-to-treat population included 120 patients (median time since diagnosis 0.95 months). The ACR20 response rate at study end was 69.0% (95%CI 60.5%, 77.4%). Response rates were significantly lower (P = 0.025) in the loading-dose group [58.5% (45.2%, 71.8%)] than in the fixed-dose group [77.8% (67.5%, 88.0%)]. Three-month ACR50, ACR70 and DAS28 response rates were 41.4%, 17.7% and 81.7%, respectively, with no significant differences between groups. Adverse events occurred in 53.7% (loading-dose group) and 49.3% (fixed-dose group) of patients, most frequently diarrhoea and elevated hepatic enzymes; these occurred more frequently and earlier in treatment when the loading dose was used. Conclusion. LEF was effective in DMARD-naïve patients with early disease. No incremental benefit was observed with the use of a loading dose, which may be associated with an increased initial rate of adverse events. The advantage of LEF initiation with a loading dose is not confirmed in this population. Trial Registration. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00596206. [ABSTRACT FROM AUTHOR]

Objective. To describe the results of different statistical ways of addressing radiographic outcome affected by missing data—multiple imputation technique, inverse probability weights and complete case analysis—using data from an observational study.Methods. A random sample of 96 RA patients was selected for a follow-up study in which radiographs of hands and feet were scored. Radiographic progression was tested by comparing the change in the total Sharp–van der Heijde radiographic score (TSS) and the joint erosion score (JES) from baseline to the end of the second year of follow-up. MI technique, inverse probability weights in weighted estimating equation (WEE) and CC analysis were used to fit a negative binomial regression.Results. Major predictors of radiographic progression were JES and joint space narrowing (JSN) at baseline, together with baseline disease activity measured by DAS28 for TSS and MTX use for JES. Results from CC analysis show larger coefficients and s.e.s compared with MI and weighted techniques. The results from the WEE model were quite in line with those of MI.Conclusion. If it seems plausible that CC or MI analysis may be valid, then MI should be preferred because of its greater efficiency. CC analysis resulted in inefficient estimates or, translated into non-statistical terminology, could guide us into inaccurate results and unwise conclusions. The methods discussed here will contribute to the use of alternative approaches for tackling missing data in observational studies. [ABSTRACT FROM PUBLISHER]

Objective. To characterize steroid use and compliance with glucocorticoid-induced osteoporosis (GIOP) guidelines within a large early inflammatory arthritis cohort.Methods. Using the Canadian Early Arthritis Cohort (CATCH) database, patients with inflammatory arthritis on glucocorticoids (oral, IA and i.m.) were identified. Consecutive steroid exposure was defined as using glucocorticoids for two consecutive clinic visits (at least 90 days apart). The primary outcome was the proportion of patients receiving calcium, vitamin D and a bisphosphonate among patients treated with consecutive oral glucocorticoids.Results. Six hundred and fifty-five patients were in the CATCH database, where 273 patients were identified as glucocorticoid users, of whom 48% were on oral prednisone, 38% received i.m. or IA and 13% both. The median oral daily dose of prednisone was 5 mg (interquartile range 2.5–10). Consecutive users (CUs, n = 78) compared with non-consecutive users (NUs, n = 532) showed that CUs were older (56 vs 50 years, P = 0.001); females were fewer (63% vs 74%, P = 0.04), but a similar proportion were RF positive (51% in CU vs 56% in NU, P = 0.73). For the primary outcome, rates of prophylaxis for users of consecutive oral steroids were as follows: 53% were treated with calcium, 47% with vitamin D and 25% were on a bisphosphonate. For users of oral prednisone at doses &geq;7.5 mg/day, rates of prophylaxis were as follows: 64% were treated with calcium, 57% with vitamin D and 21% were on a bisphosphonate.Conclusion. Glucocorticoid therapy is frequently used in early inflammatory arthritis. The use of calcium, vitamin D or a bisphosphonate was low among chronic glucocorticoid users and illustrates the need for more diligence in patients receiving glucocorticoids to prevent GIOP. [ABSTRACT FROM PUBLISHER]

Objectives. To evaluate the impact of clinical response on work stoppage or work absence among employed people with early RA.Methods. First-year data from the combination of MTX and etanercept trial was used. The analyses were restricted to the 205 patients working full or part time at baseline who answered questions on whether they stopped working or missed days from work in one or more of the four follow-up visits. Work stoppage referred to the first occurrence of subjects reporting stopping work. Work absence was defined as whether patients reported missed days from work. Clinical response and activity state considered included the ACR and European League against Rheumatism response criteria, 28-joint DAS (DAS-28) remission and the minimum clinically important difference of the HAQ score.Results. After adjustment for baseline characteristics, ACR70 responders were 72% less likely to stop working and 55% less likely to miss work than ACR20 non-responders (P < 0.05). Patients achieving DAS-28 remission were 54% less likely to stop work than those with DAS-28 > 3.2 (P < 0.05). Moderate improvements did not appear to effect work stoppage or missed days after adjustments.Conclusions. Results suggest that achieving clinical remission or major improvement might be necessary to significantly impact work outcomes.Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00195494. [ABSTRACT FROM PUBLISHER]

Objective. To explore possible association between disease activity at 3-month follow-up after RA diagnosis and costs over the following 4 years.Methods. Three-hundred and twenty patients with early (&leq;1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates.Results. Three months after diagnosis, a DAS-28 level of &geq;3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 &geq; 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 < 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years.Conclusions. Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years. [ABSTRACT FROM PUBLISHER]

Objectives. To characterize body composition phenotypes using a dual-energy X-ray absorptiometry (DXA) method and to explore factors potentially contributing to alterations in body composition in Vietnamese women with early RA.Methods. A total of 105 women with early RA (disease duration &leq;3 years) and 105 age-matched healthy women underwent physical examination, total and regional lean mass (LM) and fat mass (FM) with DXA. The 28-joint DAS (DAS-28) and disability using HAQ score, nutrition, physical activity and medications were recorded.Results. Means of weight and BMI were similar in RA patients and controls, but means of total body and trunk FM in RA patients were higher: 19.1 vs 16.9 kg (P = 0.007) and 10.1 vs 8.1 kg (P = 0.01), respectively, and appendicular LM was lower: 12.9 vs 14.1 kg (P = 0.02). The proportion of unhealthy body composition phenotypes (sarcopenia, overfat and sarcopenic obesity) in RA patients was higher (P < 0.001) than in controls. DAS-28 score was positively correlated with total FM and fat distribution ratio, and HAQ score was inversely correlated with appendicular LM. These body composition changes were associated with RF seropositivity, HAQ and DAS-28 scores.Conclusions. Women with early RA had a significantly higher proportion of unhealthy body composition phenotypes, higher total and truncal FM and lower appendicular LM than controls. Disease activity and disability scores were associated with unhealthy body composition. These findings suggest that clinicians should encourage muscle strengthening and fat loss in RA patients to reduce their disability. [ABSTRACT FROM PUBLISHER]

Objective. To report from early RA network (ERAN) on Years 2 and 3 28-joint DAS (DAS-28) and HAQ outcomes in newly diagnosed RA patients treated with DMARD therapies stratified to DAS-28 status after 1 year.Methods. ERAN is a prospective observational cohort of newly diagnosed RA patients, monitored and treated according to local practice. Standardized case report forms are completed at first presentation, 3–6 months, 1 year and annually thereafter.Results. A total of 418 newly diagnosed RA patients with 2 years and 302 with 3 years follow-up were identified in 22 ERAN centres from 2002 to 2008. Within their first year from registration, 67% of patients received monotherapy DMARDs, and 26% combination DMARDs including 2% were on anti-TNF therapies. Between Years 1 and 3, 60% received DMARD monotherapy, 34% combination DMARD therapy including 8% on anti-TNF therapies. Seventy-four per cent of patients with Year 1 DAS-28 <3.2 and 27% with DAS-28 3.2–5.1 achieved a DAS-28 <3.2 outcome at Year 2 [odds ratio (OR) 7.64; 95% CI 4.6, 12.6], and 71 and 35%, respectively, at Year 3 (OR 4.49; 95% CI 2.5, 7.9). Seventy-nine per cent of patients with a Year 1 DAS-28 <3.2 and 52% with DAS-28 3.2–5.1 achieved an HAQ <1.25 at Year 2 (OR 3.47; 95% CI 2.1, 5.6), and 81 and 47%, respectively, at Year 3 (OR 4.92; 95% CI 2.6, 9.0).Conclusions. In RA patients with a DAS-28 3.2–5.1 at 1 year, the likelihood of achieving a target low DAS-28 <3.2, or a low HAQ, at Years 2 or 3 is poor in a routine care setting using conventional DMARDs according to current practice. [ABSTRACT FROM PUBLISHER]

Objective. Serological markers are thought to be useful in predicting which patients with early inflammatory arthritis (EIA) will progress to RA. The objective of this study is to determine the per cent RF and anti-CCP seroconversion in EIA patients at 1–5 years of follow-up: 80% of established RA is RF or CCP positive.Methods. We conducted a systematic literature review of all English publications and recent abstracts from ACR and EULAR. Patients &geq;16 years of age with at least one swollen joint and symptoms < 2 years were included.Results. Twelve publications met the criteria: 10 studies included data on RF, while only 5 addressed anti-CCP. Sample sizes ranged from 15 to 395 and follow-up was 6–60 months. There was marked heterogeneity between studies; therefore, results could not be pooled for a meta-analysis. Baseline RF and anti-CCP positivity was also highly variable: 8–55 and 4–45%, respectively. Seroconversion rates for EIA were 1.9–5.0% at up to 30 months follow-up for RF and 1.3–8.9% at up to 60 months follow-up for anti-CCP.Conclusion. There is minimal change in RF or anti-CCP positivity up to 5 years of follow-up. Prevalence data for RF in established RA is significantly higher than the baseline values reported here. The low rates of seroconversion would suggest a lower prevalence in EIA and the reason for this difference remains unknown. It is unclear whether antibody-negative patients are more likely to remit and be lost to follow-up in established RA populations. [ABSTRACT FROM AUTHOR]

Objectives. Current UK management of RA initially employs conventional DMARDs, with biological therapy reserved for DMARD-resistant RA patients with persistently high 28-joint disease activity score (DAS-28). The aim of this study was to examine the effect on patient-reported function of persistently moderate DAS-28 despite modern step-up DMARD therapy in an early arthritis cohort. [ABSTRACT FROM PUBLISHER]

Objective. To ascertain whether a 1-year remission induction therapy with an infliximab–MTX (INF–MTX) combination in patients with early RA provided sustained benefit after INF cessation compared with conventional treatment. [ABSTRACT FROM PUBLISHER]

Objectives. RA is associated with joint destruction and cardiovascular diseases (CVDs). Possible predictors for CVD are early changes in body composition. We therefore evaluated whether lean mass of arms and legs (LMAL), total body fat mass (BFM) or truncal fat distribution (TFD) are altered early in RA, and if so, which factors are associated.Methods. We included 132 RA patients (95 women) with disease duration of ⩽12 months. Disease activity score (DAS28), HAQ, BMI, comorbidity, smoking and medications were recorded. Total and regional lean mass and fat mass were measured with DXA. Data were compared with 132 age- and gender-matched controls, and possibly associated factors were analysed in linear regression models.Results. LMAL was low in patients for both women and men (P = 0.007 and <0.001, respectively). BMI (P = 0.012), BFM (P = 0.014) and TFD (P < 0.001) were higher than expected in RA women. In bivariate analyses, all adjusted for age and current smoking, disease duration was independently associated with low LMAL in women (P = 0.021). High BFM was associated with HAQ × disease duration in men (P = 0.033) and DAS28 in women (P = 0.011). High TFD was associated with a history of diabetes or CVD in men with RA (P = 0.005).Conclusions. Low LMAL, high BFM and high TFD are present in early RA patients. The long-term significant consequences of these abnormalities need to be determined. [ABSTRACT FROM PUBLISHER]