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ID PMID Title PublicationDate abstract
23136241 Forget personalised medicine and focus on abating disease activity. 2013 Jan In this viewpoint, we summarise three different lines of evidence suggesting that current biological therapies directed at different molecules or cells have similar efficacy in rheumatoid arthritis and target similar populations of patients; therefore, distinct biological effects of targeted therapies may not account for differences in response. Moreover, currently available individual biomarkers or multiple biomarker sets do not provide information beyond that conveyed by clinical disease activity. Smart and novel research designs will have to be developed to find pertinent biomarkers. Until then, the focus of clinicians may have to solely rest on clinical disease activity assessment and targeting remission or low disease activity rapidly.
24924839 Interleukin-23 and its correlation with disease activity, joint damage, and functional dis 2014 Jul The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire-Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019-1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021-1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.
24480192 Identifying factors hampering physical activity in longstanding rheumatoid arthritis: what 2014 Mar OBJECTIVES: To identify factors hampering the level of physical activity in longstanding rheumatoid arthritis (RA) patients, and to evaluate the effects of glucocorticoid therapy on physical activity. METHODS: Patient characteristics, disease characteristics and cardiovascular parameters were recorded in 170 patients, who participated in a study about glucose metabolism in longstanding RA treated with or without glucocorticoids. Disease activity scores (DAS28) were calculated and x-rays of hands and feet were taken and scored according to the Sharp van der Heijde score (SHS). Participants completed the health assessment questionnaire and short questionnaire to assess health-enhancing physical activity (SQUASH), which reflect physical disability and physical activity, respectively. Adherence rates to recommendations on physical activity were calculated, and patients were categorised as fully adhering, insufficiently adhering (adherence on less than the recommended number of days per week) or inactive (adherence on none of the days). RESULTS: Forty-four percent of the patients showed adherence to the recommended minimum level of physical activity, and 22% were classified as inactive. Higher DAS28 and SHS, glucocorticoid therapy, and presence of cardiovascular risk factors were associated with lower total SQUASH physical activity scores univariately. In a multivariate model, higher age, higher body mass index (BMI), higher DAS28, and higher SHS negatively influenced the score significantly; cardiovascular risk factors and glucocorticoid therapy were no longer significantly influencing physical activity. CONCLUSIONS: Physical activity in longstanding RA is hampered by higher age, higher BMI, higher disease activity, and more radiographic joint damage. Glucocorticoid therapy was not identified as independent risk factor in multivariate analyses.
24144300 Can routine clinical measures predict ultrasound-determined synovitis and remission in rhe 2014 Jan OBJECTIVES: The purpose of this study was to determine if routine clinical measures can predict the presence and severity of ultrasound synovitis in rheumatoid arthritis (RA) patients. METHODS: Bilateral 1-5 MCP (metacarpopharangeal) and wrist joints were examined using power Doppler (PD) ultrasound (US). Correlations between PD scores and routine clinical measures of RA - swollen joint count (SJC), tender joint count, patient's global assessment (GA), physician's GA, CRP, ESR, MMP-3, RF and anti-CCP antibody - were determined and used to identify significant predictors of PD score. Clinical measures were then compared between two groups (patients with and without PD) and analysed using multiple logistic regression, to derive a model that predicted the absence of PD signals. RESULTS: SJC was the most significant predictor of PD score (R2 = 0.4566, p value <0.0001), but was an inadequate predictor of PD signal remission. However, the combination of Steinbrocker's stage I or II (odds ratio [OR] 9.23, p=0.0049), SJC=0 in 1-5 MCP and wrist joints on both sides (OR 6.60, p=0.0039), and SDAI (or CDAI) remission (OR 5.06, p=0.0450) had a positive predictive value of 100%, predicting the absence of PD signals in all study patients meeting the 3 criteria. CONCLUSIONS: PD score and absence of PD signals can be predicted using routine clinical measures. When used in combination, Steinbrocker's stage, SJC and SDAI (or CDAI) can estimate disease activity and identify patients likely to have synovitis and requiring US.
23492740 New learnings on the pathophysiology of RA from synovial biopsies. 2013 May PURPOSE OF REVIEW: To critically appraise the literature related to the pathophysiology of rheumatoid arthritis (RA) focusing on the contribution of synovial tissue pathology (synovitis) in determining diverse clinical outcome/therapeutic response. RECENT FINDINGS: RA synovitis is highly heterogeneous with diverse cellular and molecular signatures (pathotypes) emerging as potential taxonomic classifiers of disease phenotypes.The challenge is to understand mechanistically the sophisticated interplay between systemic disease 'initiators' and joint-specific 'localizing/perpetuating' factors leading to disparate coupling of inflammation/tissue-destructive pathways and disease outcome. Synovial tissue analysis has been instrumental in enhancing understanding of R0A pathogenesis and developing targeted DMARD-biologic therapies. The next step is to elucidate the relationship of different synovial pathotypes/molecular signatures with therapeutic response/resistance in randomized clinical trials in order to develop effective therapies for 'resistant' patients. The development of ultrasound-guided synovial biopsy as a rapid, safe and well tolerated procedure that enables synovial tissue collection from most joints/patients will facilitate such studies. SUMMARY: RA is a heterogeneous clinical and pathobiological entity. Specific pathways within synovial tissues are emerging as associated with diverse clinical evolution and therapeutic response/resistance that, if confirmed in randomized clinical trials, may lead to the development of synovial tissue analysis as a potential clinical tool for patient stratification.
25240685 Cartilage repair in vivo: the role of migratory progenitor cells. 2014 Nov The most common diseases of the joints and its tissues are osteoarthritis and rheumatoid arthritis, with osteoarthritis being anticipated to be the fourth leading cause of disability by the year 2020. To date, no truly causal therapies are available, and this has promoted tissue engineering attempts mainly involving mesenchymal stem cells. The goal of all tissue repairs would be to restore a fully functional tissue, here a hyaline articular cartilage. The hyaline cartilage is the most affected in osteoarthritis, where altered cell-matrix interactions gradually destroy tissue integrity. In rheumatoid arthritis, the inflammatory aspect is more important, and the cartilage tissue is destroyed by the invasion of tumor-like pannus tissue arising from the inflamed synovia. Furthermore, the fibrocartilage of the meniscus is clearly involved in the initiation of osteoarthritis, especially after trauma. Recent investigations have highlighted the role of migratory progenitor cells found in diseased tissues in situ. In osteoarthritis and rheumatoid arthritis, these chondrogenic progenitor cells are involved in regeneration efforts that are largely unsuccessful in diseased cartilage tissue. However, these progenitor cells are interesting targets for a cell-based regenerative therapy for joint diseases.
25371467 The natural history of the rheumatoid shoulder: a prospective long-term follow-up study. 2014 Nov The purpose of this study was to evaluate the natural history of rheumatoid disease of the shoulder over an eight-year period. Our hypothesis was that progression of the disease is associated with a decrease in function with time. A total of 22 patients (44 shoulders; 17 women, 5 men, (mean age 63)) with rheumatoid arthritis were followed for eight years. All shoulders were assessed using the Constant score, anteroposterior radiographs (Larsen score, Upward-Migration-Index (UMI)) and ultrasound (US). At final follow-up, the Short Form-36, disabilities of the arm, shoulder and hand (DASH) Score, erythrocyte sedimentation rate and use of anti-rheumatic medication were determined. The mean Constant score was 72 points (50 to 88) at baseline and 69 points (25 to 100) at final follow-up. Radiological evaluation showed progressive destruction of the peri-articular structures with time. This progression of joint and rotator cuff destruction was significantly associated with the Constant score. However, at baseline only the extent of rotator cuff disease and the UMI could predict the Constant score at final follow-up. A plain anteroposterior radiograph of the shoulder is sufficient to assess any progression of rheumatoid disease and to predict functional outcome in the long term by using the UMI as an indicator of rotator cuff degeneration.
22476781 Musculoskeletal ultrasonography assists the diagnostic performance of the 2010 classificat 2013 Jan OBJECTIVE: We investigated whether musculoskeletal ultrasonography (MSKUS) assists the diagnostic performance of the 2010 rheumatoid arthritis (RA) classification criteria. METHODS: Sixty-nine early arthritis patients were consecutively enrolled. None of the patients had been treated. In MSKUS of bilateral wrist and finger joints from 22 sites, the findings obtained by gray-scale and power Doppler (PD) assessment were graded on a semiquantitative scale from 0 to 3. Plain magnetic resonance imaging (MRI) of both wrist and finger joints was also examined. Diagnosis of RA was defined by the initiation of disease-modifying antirheumatic drugs within the first 3 months. The diagnostic performance of the patients was evaluated at entry using 2010 RA classification criteria in conjunction with MSKUS. RESULTS: The indispensable MSKUS finding for differentiating RA was the presence of a PD grade 2 or 3 that was superior to 2010 RA classification criteria or MRI-proven bone edema. We propose that the decision tree algorithm of 2010 RA classification criteria with PD grade 2 or 3 reveals the best discriminative ability. CONCLUSION: MSKUS, especially with a strong PD signal, is very useful to assist the diagnostic performance of the 2010 RA classification criteria in the early recognition of RA.
24670128 Identification of clinical parameters associated with serum oxidative stress in patients w 2014 Nov OBJECTIVES: Reactive oxygen species (ROS) are considered to be involved in the pathobiology of rheumatoid arthritis (RA); however, their association with disease activity has not been elucidated. In this study, we measured reactive oxygen metabolites (ROM) in patients with RA using a new Free Radical Analytical System and determined clinical parameters associated with ROM. METHODS: One hundred and fifty-two patients with RA and 80 patients with diabetes mellitus (DM) were included in this observational study. To measure ROM, the d-ROM test was performed on blood samples drawn from all subjects. The correlation between ROM and biomarkers, disease activity, doses of methotrexate (MTX), and prednisolone (PSL) were investigated. RESULTS: There were significant, positive correlations between ROM and CRP, matrix metalloproteinase 3 (MMP3), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). Multiple regression analysis revealed that CRP and DAS28-ESR were correlated with ROM. CONCLUSIONS: The serum level of ROM was associated with CRP and DAS28-ESR, suggesting that ROM, in conjunction with CRP and MMP3, may be able to be used as a new biological disease marker to evaluate the disease activity of RA.
24595462 Yttrium-90 distribution following radiosynoviorthesis of the knee joint in rheumatoid arth 2014 Aug OBJECTIVE: To examine yttrium-90 distribution 1 and 72 h following its injection into a knee joint in patients with rheumatoid arthritis (RA). METHODS: In 14 RA patients we injected yttrium-90 into the affected knee joint using lateral approach. To assess the radioisotope distribution in the joint, the superimposed sequential SPECT and CT imaging was performed 1 and 72 h after the injection. We analyzed the percentage of radioisotope distribution in three predefined compartments of the knee joint (lower, upper medial, upper lateral). RESULTS: After 1 and 72 h, the mean percentage distributions were, respectively, 7.14 and 23.07% in lower; 21.42 and 15.38% in upper medial, and 71.42 and 61.53% in upper lateral compartment. The percentage of isotope deposition did not change significantly with time in any of the compartments (all p > 0.26). The deposition of isotope, both at 1 and 72 h, was significantly greater in upper lateral compartment, where the injection was performed, than in all other compartments (all p < 0.05). CONCLUSIONS: Using the SPECT/CT hybrid method, we proved that the majority of isotope is located at the compartment adjacent to the injection. Two injections targeting different compartments might improve the clinical efficacy of the procedure.
24618052 Use of rituximab to treat a patient with coexistence of rheumatoid arthritis and ankylosin 2018 Oct Coexistence of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is rare. Tumor necrosis factor (TNF) inhibitor has been highly successful in controlling inflammation in many patients with AS or RA. Rituximab, which is a chimeric anti-CD20 monoclonal antibody, has been proven effective in RA. Whether rituximab may be effective in AS is presently unclear. Here we report the 18 months follow-up result of a coexisting AS and RA TNF inhibitor failed patient that was treated successfully with rituximab.
25284481 IRF5rs2004640 single nucleotide polymorphism is associated with susceptibility to rheumato 2014 Nov Polymorphism of interferon regulatory factor 5 (IRF5), a latent transcription factor gene has been associated with various auto-immune diseases. Our aim was to study the IRF5rs2004640 gene polymorphism and its association with disease susceptibility, disease phenotype and treatment response in South Indian Tamil patients with rheumatoid arthritis (RA).The study was conducted on 217 RA patients fulfilling the American College of Rheumatology (ACR) 2010 criteria and 482 healthy controls (HCs) without family history of autoimmune disease. The IRF5rs2004640 genotyping was performed using a TaqMan 5' allelic discrimination assay. We found that the IRF5rs2004640T allele [P < 0.0001, odds ratio (OR) 3.25, 95% confidence interval (CI) 2.55-4.12] and TT genotype (P < 0.0001, OR 4.60, 95% CI 3.23-6.57) were significantly more frequent in RA patients as compared with HCs. No association was found between IRF5rs2004640 polymorphism, clinical manifestations, autoantibody profile and treatment response. IRF5rs2004640 T (mutant) allele may be a susceptibility factor conferring risk for RA in South Indian Tamils, whereas G allele (wild type) may be protective.
23948822 Low back pain in patients with rheumatoid arthritis: clinical characteristics and impact o 2013 OBJECTIVES: The aim of this study was to assess the point prevalence of low back pain (LBP) in patients with rheumatoid arthritis (RA); and to compare radiological and clinical aspects, as well as impact of LBP on health related quality of life (QoL), depression and disability in control patients with mechanical LBP (mLBP). METHODS: Patients with RA and patients with mLBP of at least 3 months duration were consecutively recruited. All patients were examined and underwent lumbar X-ray and magnetic resonance (MR) imaging. Disc intensity, annulus fibrosis rupture, herniated nucleus pulposus (bulging, protrusion, extrusion or sequestration), stenosis, Schmorl nodes, hemangiomas, Tarlov cysts, Type I or II degeneration, ligamentum flavum hypertrophy and loss of lordosis were assessed on MR. Assessments included QoL and disability scales like RAQoL, Short Form-36, Health Assessment Questionnaire (HAQ) and Oswestry Disability Index (ODI) and depression and anxiety scales as well. RESULTS: Chronic LBP coexisted in 64.5% of patients with RA. Patients with LBP had higher scores on VAS-LBP compared to patients with RA+LBP. Additionally, patients with RA+LBP had the poorest scores on quality of life, functional disability and depression. Patients with mLBP had more frequent clinical manifestations and neurologic deficits. Patients with RA+LBP had more frequent Schmorl nodes compared to patients with mLBP. CONCLUSION: The association of RA with LBP leads to a significant decrease in the functional capacity and QoL as well as increase in depression risk. Appropriate diagnostic procedures and treatments should be administered to avoid further deterioration in functional disability and QoL.
25260860 Psychological distress across twelve months in patients with rheumatoid arthritis: the rol 2015 Feb OBJECTIVE: Mindfulness may diminish effects of adversities on psychological well-being in medical patients, but studies are scarce, especially in patients with rheumatoid arthritis (RA). The purpose was to examine the prospective moderating effect of mindfulness regarding psychological distress associated with disease activity and disability in patients with RA. METHODS: Two-hundred-and-one patients with RA (mean age 57.4 ± 11.7, 55% women) completed questionnaires at baseline and at six and twelve month follow-up. Disease activity score was assessed by the rheumatologist. RESULTS: Controlled for potential confounders, mixed linear model analyses showed a strong prospective association of higher baseline mindfulness with lower psychological distress up to the twelve month follow-up (p<.001). In addition, a mindfulness by disability by time interaction showed that higher baseline mindfulness was associated with lower disability related psychological distress at follow-up (p=.022). CONCLUSION: Findings are in line with the hypothesis that mindfulness may protect against psychological distress associated with disability in RA. Potential benefits of mindfulness-based interventions for prevention should be examined in this population.
24315053 Is there a place for initial treatment with biological DMARDs in the early phase of RA? 2013 Aug The use of biological disease-modifying antirheumatic drugs (bDMARDs) has changed the face of rheumatoid arthritis (RA). Achieving remission, normal function and prevention of joint damage are now possible for many patients with RA. In clinical practice, however, particularly with cost considerations, bDMARDs are usually prescribed after failure of one or more conventional synthetic DMARDs. With evidence that early treatment has a greater impact than later on, the question regarding initial bDMARD therapy and their potential role within a window of opportunity to influence disease outcomes remain. The increasing emphasis on early diagnosis and research into the preclinical phase of the disease also heralds the question, 'Can bDMARDs prevent the development of RA?' The aim of this review is to review randomised controlled trials with bDMARDs as initial therapy in early RA and to discuss their role in early disease.
24941928 "A gift from heaven" or "This was not for me". A mixed methods approach to describe experi 2015 Mar Most persons with rheumatoid arthritis (RA) do not perform health-enhancing physical activity (HEPA). Evaluations of innovative HEPA programs need to be complemented with descriptive and qualitative data from the users. The aim of this mixed methods study was to explore and describe how a subgroup of the RA population perceives participation during the first year of an outsourced 2-year HEPA program. Data were collected by a study-specific postal survey to 220 program participants (response rate 87%, n = 191) and by interviews with a purposefully selected subsample of 35, including completers and dropouts. The survey data were analyzed by descriptive statistics and the interviews by qualitative content analysis.The survey demonstrated increased self-reported physical activity in 165 participants (86%). After the first year of the program, participants reported having performed "regular" or "periodical" circuit training (78%) and physical activity in daily life (92%). The most valued program components were circuit training and physical activity in daily life, both rated median 5/5. Coach support, prompts by text messages, and expert lectures were rated median 4/5. Five categories emerged from the interviews describing expectations, facilitators, gains, maintenance, and obstacles/suggestions for improvement of the program. The results demonstrate that HEPA outside health care is highly appreciated by a subgroup of the RA population. Professional coaching and prompts by text messages seem to be particularly useful facilitators. Individual preferences emphasize the need to tailor settings, exercise formats, and behavioral support for HEPA even in a narrow, self-selected group with RA.
25489637 High levels of metastasis-inducing S100A4 protein and treatment outcome in early rheumatoi 2015 Feb Abstract The aim of this study was to evaluate the role of S100A4 as a biomarker in patients with early rheumatoid arthritis (RA). S100A4 levels were measured in 59 patients with early RA and in 41 healthy controls. The association between the S100A4 levels and the treatment outcome after 12 months was determined using multivariate regression analysis. Serum S100A4 levels were significantly higher in the patients with early RA than in the healthy subjects and significantly decreased after 3 months of treatment. Diseases activity at 12 months was significantly higher in female patients who had initially high levels of S100A4. Persistently high S100A4 levels predicted poor treatment outcome and S100A4 may thus represent promising biomarker for assessing treatment response in patients with RA.
23305590 Clinical presentation, burden of disease and treatment in young-onset and late-onset rheum 2013 Mar OBJECTIVES: The aim of this study is to compare clinical features and treatment of young onset rheumatoid arthritis with late-onset rheumatoid arthritis. METHODS: Nine thousand five hundred forty-one patients with rheumatoid arthritis (RA) enrolled in the national database of the German Collaborative Arthritis Centres in 2007-2009 were stratified by age at disease onset: up to 65 years (YORA), >65 years (LORA). To enable unbiased comparisons between the two groups despite their systematic differences in age and disease duration, we performed two separate matched-pairs analyses: the impact of current age was assessed by matching YORA and LORA patients for disease duration and sex (n=1,550 pairs). To identify the influence of disease duration, a second sample matched for age and sex (n=1,158 pairs) was drawn. RESULTS: At identical age, YORA patients had higher disease activity (DAS28), worse functional capacity and were less frequently in remission when compared with LORA patients. YORA patients also suffered more frequently from RA-related co-morbidities such as cardiovascular disease, chronic renal disease and osteoporosis. Matched for disease duration, there were no differences between the two groups concerning disease severity and remission rates, global health or pain intensity. Independent of age or disease duration, YORA patients reported more sleep disorders and fatigue. LORA patients received significantly fewer synthetic or biologic DMARDs than YORA patients. CONCLUSIONS: Duration of RA, rather than age, explains differences in disease burden between YORA and LORA patients. The lower prescription rates of synthetic and in particular biologic DMARDs, despite lower remission rates, indicate a potential treatment deficit in older patients.
23981751 Low body mass index is associated with impaired quality of life in patients with rheumatoi 2013 Jun AIM: To investigate the relationship between quality of life (QOL) and rheumatoid chachesia, malnutrition in patients with rheumatoid arthritis (RA). METHODS: EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) and Japanese Health Assessment Questionnaire (JHAQ) scores, body mass index (BMI), arm muscle area (AMA) and clinical indicators were measured in 385 RA patients. One-way analysis of variance for obtained data was conducted among three groups: 131 with low BMI (< 20), 163 with moderate (20-25) and 91 with high BMI (≥25). Then multiple regression analyses for JHAQ and EQ5D scores with nutritional and clinical indicators as independent variables were performed. RESULTS: EQ5D and JHAQ scores were significantly lower and higher, respectively, in the low BMI group than those in the moderate BMI group. Clinical indicators including doses of corticosteroid were similar among the three groups except for disease duration. Disease activity score (DAS) 28, disease duration, C-reactive protein and AMA were significant variables in the regression model for EQ5D. CONCLUSION: Low BMI deteriorates the QOL of RA patients. Muscle protein loss apparently leads to a reduction in BMI and QOL.
23505543 Ultrasonographic assessment of enthesitis in HLA-B27 positive patients with rheumatoid art 2013 INTRODUCTION: HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA) has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US). METHODS: The Madrid Sonography Enthesitis Index (MASEI) was applied to the US assessment of 41 HLA-B27 positive and 41 matched HLA-B27 negative patients with longstanding RA. Clinical characteristics including explorations aimed to evaluate spondyloarthrtitis and laboratory tests were also done. RESULTS: A significant degree of abnormalities in the entheses of the patients with RA were found, but the MASEI values, and each of its components including the Doppler signal, were similar in HLA-B27 positive and negative patients. An increase of the MASEI scores with age was identified. Differences in two clinical features were found: a lower prevalence of rheumatoid factor and a more common story of low back pain in the HLA-B27 positive patients than in the negative. The latter was accompanied by radiographic sacroiliitis in two HLA-B27 positive patients. No other differences were detected. CONCLUSION: We have found that HLA-B27 positive patients with RA do not have more enthesitis as assessed with US than the patients lacking this HLA allele. However, HLA-B27 could be shaping the RA phenotype towards RF seronegativity and axial involvement.