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ID PMID Title PublicationDate abstract
23486412 The potential use of expression profiling: implications for predicting treatment response 2013 Jul Whole genome expression profiling, or transcriptomics, is a high throughput technology with the potential for major impacts in both clinical settings and drug discovery and diagnostics. In particular, there is much interest in this technique as a mechanism for predicting treatment response. Gene expression profiling entails the quantitative measurement of messenger RNA levels for thousands of genes simultaneously with the inherent possibility of identifying biomarkers of response to a particular therapy or by singling out those at risk of serious adverse events. This technology should contribute to the era of stratified medicine, in which patient specific populations are matched to potentially beneficial drugs via clinical tests. Indeed, in the oncology field, gene expression testing is already recommended to allow rational use of therapies to treat breast cancer. However, there are still many issues surrounding the use of the various testing platforms available and the statistical analysis associated with the interpretation of results generated. This review will discuss the implications this promising technology has in predicting treatment response and outline the various advantages and pitfalls associated with its use.
23592710 Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a syst 2014 Jan BACKGROUND: The 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) were developed to improve the identification of individuals for studies of RA. We aimed to summarise the performance of the criteria based on the published literature. METHODS: We performed a systematic literature search to identify all studies investigating the 2010 criteria and reporting data allowing to calculate sensitivity (SENS), specificity (SPEC), and positive and negative predictive values. Where possible, meta-analysis was performed. RESULTS: Seventeen full articles (total 6816 patients) and 17 meeting abstracts (total 4004 patients) fulfilled the inclusion criteria. Pooled sensitivity and specificity for RA (defined by different reference standards) were 0.82 (95% CI 0.79-0.84) and 0.61 (0.59-0.64). Results were comparable for different reference standards: for initiation of methotrexate pooled sensitivity was 0.85 (0.83-0.86) and specificity was 0.52 (0.49-0.54); for initiation of any disease modifying antirheumatic drug they were 0.80 (0.79-0.82) and 0.65 (0.61-0.68), respectively; and for expert opinion 0.88 (0.86-0.90) and 0.48 (0.35-0.52). No differences were observed for use of different types of joint counts. Eight studies and five meeting abstracts directly compared 1987 and 2010 criteria using different reference standards within different target populations showing higher overall sensitivity (+0.11 compared with 1987 criteria) at the cost of lower overall specificity (-0.04). CONCLUSIONS: Two years after their publication, the 2010 ACR/EULAR criteria have been widely tested in the community. They are sensitive to detect cases of RA among various target populations, independent of how the latter is referenced.
23876775 The class III histone deacetylase sirtuin 1 in immune suppression and its therapeutic pote 2013 Jul 20 Rheumatoid arthritis (RA) is a chronic debilitating disease of the joints. Both the innate and adaptive immune responses participate in the development and progression of RA. While several therapeutic reagents, such as TNF-α agonists, have been successfully developed for the clinical use in the treatment of RA, more than half of the patients do not respond to anti-TNF therapy. Therefore, new therapeutic reagents are needed. Recent studies have shown that sirtuin 1 (Sirt1), a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, is a critical negative regulator of both the innate and adaptive immune response in mice, and its altered functions are likely to be involved in autoimmune diseases. Small molecules that modulate Sirt1 functions are potential therapeutic reagents for autoimmune inflammatory diseases. This review highlights the role of Sirt1 in immune regulation and RA.
24737176 Autoimmune priming, tissue attack and chronic inflammation - the three stages of rheumatoi 2014 Jun Extensive genome-wide association studies have recently shed some light on the causes of chronic autoimmune diseases and have confirmed a central role of the adaptive immune system. Moreover, better diagnostics using disease-associated autoantibodies have been developed, and treatment has improved through the development of biologicals with precise molecular targets. Here, we use rheumatoid arthritis (RA) as a prototype for chronic autoimmune disease to propose that the pathogenesis of autoimmune diseases could be divided into three discrete stages. First, yet unknown environmental challenges seem to activate innate immunity thereby providing an adjuvant signal for the induction of adaptive immune responses that lead to the production of autoantibodies and determine the subsequent disease development. Second, a joint-specific inflammatory reaction occurs. This inflammatory reaction might be clinically diagnosed as the earliest signs of the disease. Third, inflammation is converted to a chronic process leading to tissue destruction and remodeling. In this review, we discuss the stages involved in RA pathogenesis and the experimental approaches, mainly involving animal models that can be used to investigate each disease stage. Although we focus on RA, it is possible that a similar stepwise development of disease also occurs in other chronic autoimmune settings such as multiple sclerosis (MS), type 1 diabetes, and systemic lupus erythematosus.
23684699 Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheu 2013 Sep The lungs are frequently involved in Connective Tissue Diseases (CTDs). Interstitial lung disease (ILD) is one of the most common pleuropulmonary manifestations that affects prognosis significantly. In practice, rheumatologists and other physicians tend to underestimate the impact of CTD-ILDs and diagnose respiratory impairment when it has reached an irreversible fibrotic stage. Early investigation, through clinical evidence, imaging and - in certain cases - lung biopsy, is therefore warranted in order to detect a possible ILD at a reversible initial inflammatory stage. In this review, we focus on lung injury during CTDs, with particular attention to ILDs, and examine their prevalence, clinical manifestations and histological patterns, as well as therapeutic approaches and known complications till date. Although several therapeutic agents have been approved, the best treatment is still not certain and additional trials are required, which demand more knowledge of pulmonary involvement in CTDs. Our central aim is therefore to document the impact that lung damage has on CTDs. We will mainly focus on Rheumatoid Arthritis (RA), which - unlike other rheumatic disorders - resembles Idiopathic Pulmonary Fibrosis (IPF) in numerous aspects.
25365082 Joint counts in inflammatory arthritis. 2014 Sep OBJECTIVES: Counting the number of tender and swollen joints is an important aspect of assessing patients with an inflammatory arthritis. We provide a comprehensive overview of joint counts in inflammatory arthritis. This spans how they are undertaken, their use in clinical and research settings, their limitations and standardisation and who can perform them. METHODS: We reviewed the literature surrounding joint counts in inflammatory arthropathies, with a specific focus on rheumatoid arthritis (RA). RESULTS: The current widely used joint count assesses 28 peripheral joints. In RA these are usually incorporated in a composite score of disease activity, termed the disease activity score on a 28-joint count (DAS28). Assessing 28 joints has a strong 'floor-effect' with most patients in routine practice having low swollen and tender joint counts. Marked between-observer variation exists in joint count scores; although the variation in tender joint counts can be reduced by standardised training its impact on swollen joint counts is uncertain. Fibromyalgia can have a marked impact on tender joint count scores, resulting in a disproportionately high tender joint count to swollen joint count ratio. Although there is evidence that patient-assessed tender joint counts correlate well with those undertaken by physicians, patients are limited assessors of synovitis. CONCLUSIONS: Although joint counts provide an important objective measure of disease activity in clinical practice, they have a number of limitations. Future research may provide a more robust clinical assessment for disease activity in inflammatory arthropathies, which overcomes these issues.
23274519 Postpublication validation of the 2010 American College of Rheumatology/European League Ag 2013 Mar PURPOSE OF REVIEW: To summarise the results of the validation studies testing the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) to date and highlight the areas for future research. RECENT FINDINGS: The 2010 ACR/EULAR classification criteria for RA were developed aiming to identify patients early in the natural history of the disease. Validation studies conducted since their publication have demonstrated that, compared with the 1987 ACR criteria for RA, the 2010 criteria identify more patients earlier in the disease course. Sensitivity for the initiation of disease-modifying antirheumatic drugs and persistent disease is increased, with decreased specificity. Patients who are seronegative may not satisfy the 2010 criteria despite meeting the 1987 criteria at presentation. The 2010 criteria may also incorrectly classify some patients with self-limiting disease as RA. SUMMARY: The 2010 criteria appear to be superior to the 1987 criteria in terms of identifying individuals with early RA. Their validity in established disease and their ability to predict worse prognosis in the long term have yet to be determined.
24777778 Associations between functional TNFR2 196 M/R polymorphisms and susceptibility to rheumato 2014 Nov Several studies have examined the effects of tumor necrosis factor receptor (TNFR) 1 +38 A/G and TNFR2 196 M/R polymorphisms on susceptibility to RA and have reported conflicting results. The purpose of this study was to examine whether the TNFR1 +38 A/G and TNFR2 196 M/R polymorphisms are associated with RA susceptibility. We performed a literature search using the Medical Literature Analysis and Retrieval System Online and Embase citation indices, and conducted a meta-analysis to examine the association between the TNFR1 +38 A/G and TNFR2 196 M/R polymorphisms and RA. Our meta-analysis included a total of 13 studies from 11 articles, consisting of 11 studies of the TNFR2 polymorphism (2,092 cases and 1,483 controls), and two studies of the TNFR1 polymorphism (672 cases and 288 controls). The meta-analysis revealed a significant association between the TNFR2 196 RR genotype and RA risk (OR 1.737, 95 % CI 1.275-2.367, P = 4.6 × 10(-5)). Stratification by ethnicity indicated an association between the TNFR2 196 RR genotype and RA in Europeans (OR 2.054, 95 % CI 1.305-3.232, P = 0.002), but not in East Asians (OR 1.596, 95 % CI 0.642-3.971, P = 0.314). Analysis using a homozygote contrast model showed the same pattern for the TNFR2 196 RR genotype in a European and East Asian population. However, no association was found between the TNFR1 +36 A/G polymorphism and RA in a European population. Our meta-analysis demonstrated that the functional TNFR2 196 M/R polymorphism is associated with susceptibility to RA in the European population.
25196669 Absence of protective effect of oral contraceptive use on the development of rheumatoid ar 2014 Sep AIM: To investigate the association between oral contraceptive (OC) use and development of rheumatoid arthritis (RA). METHOD: We conducted a systematic review and meta-analysis based on observational studies. Summary estimates were obtained using fixed- or random-effects models as appropriate. Dose-response meta-analysis, subgroup analysis, cumulative meta-analysis, sensitivity analysis and publication bias tests were performed. RESULTS: Our meta-analysis of 28 studies included 18 case-control, three nested case-control, and seven cohort studies. In case-control studies, the risk of RA of ever, current and past OC users was 0.69 (95% confidence interval [CI], 0.53-0.89), 0.71 (95% CI, 0.48-1.06) and 0.67 (95% CI, 0.44-1.01), respectively, compared to that of never OC users. In prospective studies, the corresponding odds ratios (ORs) of ever, current and past OC use were 1.00 (95% CI, 0.87-1.15), 0.93 (95% CI, 0.70-1.23) and 0.93 (95% CI, 0.78-1.12), respectively. A cumulative meta-analysis showed that the pooled ORs moved to the midline with an increase in sample size as years passed. There was an inverse association between OC use and severity of RA (OR, 0.41; 95% CI, 0.22-0.78). Dose-response meta-analysis of the study data revealed that the association between OC use and risk of RA was independent of duration of OC use. CONCLUSION: OC use has no protective effect on RA onset, but appears to prevent progression to severe RA. In addition, OC use has a lower protective effect on the risk of RA with change in OC composition. Finally, no cumulative effect was found between OC use and risk of RA.
23961681 [Rehabilitation therapy according to the disease condition and functional status of the pa 2013 Jul Rehabilitation for the patients with rheumatoid arthritis(RA), such as exercise therapy, application of splints and patient education, has contributed to the improvement in both impairments and disabilities due to the dysfunction of locomotive systems. Recent progress in drug therapy has influenced the rehabilitation approach toward the RA, because an effective pain management by itself facilitates ease of movement and improves the deteriorated locomotive functions. Early initiation of exercise therapy is reported to prevent a reduction in grip power under the conventional drug-therapy. Moreover, it is also reported that the exercise in addition to the biologics have shown better effects in the functional recovery of upper extremities in comparison with the regimen of biologics alone. While many patients have benefited from the recent advances in drug therapy, several patients still suffer impairments and disabilities without benefits of biologics due to long disease durations before biologics treatment, adverse effects of drugs and financial problems. The suggestions by EULAR, 'treat to target (T2T)' proposed that the goal of RA treatment should be to maximize long-term health-related quality of life through control of symptoms, prevention of structural damage, normalization of function and social participation. This is in the same way of rehabilitation. Though the objectives and methods of rehabilitation vary for individual patients, it should be appropriately prescribed for every individual patient based on evaluation of the patients' disabilities in order to enhance their QOL as well as ADL.
24219039 Evidence that the strategy is more important than the agent to treat rheumatoid arthritis. 2013 Eight major "strategy trials" in rheumatoid arthritis (RA) are reviewed, with protocol-driven escalation of combinations of methotrexate and other small molecule non-biological disease modifying antirheumatic drugs (DMARDs). All documented the value of intensive treatment adjusted according to quantitative data, generally a disease activity score (DAS) or its 28 joint count version (DAS28). Three of the 8 trials, TICORA, Dutch DAS-driven care, and CAMERA, may be termed "pure strategy trials," to com- pare a protocol-driven "intensive" strategy to usual care. Five other trials, BeSt, CIMESTRA, TICORA 2, Step-down versus step-up, and TEAR, may be termed "hybrid trials," in which an initial parallel design was supplemented with incremental protocol-driven intensification of treatment. A strategy of aiming for low disease activity or remission appears more important than the specific agent used. In group data, the proportion of good responses seen in these trials with combinations of non-biologic, small molecule DMARDs are comparable to data from clinical trials of biological agents although responses appear more rapid with biological agents, and certain individual patients may require a biologic agent for adequate control. These trials also illustrate the value of a quantitative index, monitored frequently for rational intensification of therapy. The data make a compelling case for both routine monitoring with a quantitative index and consideration of routine adjustment of therapy at each visit. Combinations of methotrexate with other non-biologic DMARDs and glucocorticoids, toward a target of low disease activity or remission, may improve outcomes for patients with RA at levels similar to biologic agents in many patients.
23848441 The effects of TNF α antagonist therapy on bone metabolism in rheumatoid arthritis: a sys 2013 Dec Osteoporosis is a common complication observed in rheumatoid arthritis (RA). Accelerated bone loss is always a matter of concern. The pathogenesis of RA may be important for better understanding of the bone loss. The mechanism involved in the bone loss in RA is not well understood although cytokines such as interleukin 1 and tumour necrosis factor α (TNF α) have been strongly implicated. TNF α antagonists have revolutionised the treatment of RA in the recent years. Beyond the control of disease activity in RA, accumulating evidence suggests that this form of therapy may provide beneficial effects to the bone metabolism and remodeling. An extensive search of the literature was performed in the Medline, Scopus and EBSCO databases to evaluate the documented research on the effects of TNF α antagonists in RA on bone mineral density and bone turnover markers. The available data based on our systematic review, depict a significant association between TNF α antagonists treatment and suppression of bone resorption.
24643039 Glycosylation as a marker for inflammatory arthritis. 2014 Jan 1 Changes in serum protein glycosylation play an important role in inflammatory arthritis. Altered galactosylation of immunoglobulin G (IgG) in rheumatoid arthritis attracts special attention due to the devastating nature of the disease. Studying glycosylation changes of serum proteins has been recognized as a potential strategy to provide added value regarding diagnostics, aetiopathology and therapy of inflammatory arthritic diseases. Key questions, which are approached in these fields of research, are whether or not glycosylation can be used as a complementary pre-clinical and clinical marker for disease differentiation, diagnosis, the prediction of disease course and severity as well as for the evaluation of disease therapies. These studies mainly focus on TNF antagonists, which present a new and promising way of treating inflammatory arthritis. The recent availability of new high-throughput glycoanalytical tools enables a more profound and efficient investigation in large patient cohorts and helps to gain new insights in the complex mechanism of the underlying disease pathways.
25501069 Could early rheumatoid arthritis resolve after periodontitis treatment only?: case report 2014 Dec Rheumatoid arthritis (RA) is an immune-mediated polyarthritis; currently no pathogenic agent has been identified as a disease trigger. A patient with RA, presumably caused by periodontal infection, whose remission has been observed after periodontitis treatment in absence of specific RA therapy, is reported here for the first time, to our knowledge. A 61-year-old male patient presented migrant arthritis associated with antibodies against citrullinated protein antigens positivity. The clinical features allowed to make RA diagnosis according to the 2010 European League against Rheumatism/American College of Rheumatology RA classification criteria. X-ray of the second upper molar showed chronic apical periodontitis. After its treatment, arthritis remission has been observed in the absence of specific RA therapy. It has been suggested that periodontitis may have a trigger role in RA pathogenesis. This could be explained by the enzymatic action of Porphyromonas gingivalis, probably leading to break tolerance to collagen. The identification and subsequent treatment of periodontitis should therefore be considered pivotal in RA prophylaxis and management.
24618101 Gene-environmental interaction between smoking and shared epitope on the development of an 2014 Jun OBJECTIVE: The aim of this study was to determine the gene-environment interactions of smoking and shared epitope (SE) both separately and combined on anti-cyclic citrullinated peptide (CCP) antibodies in patients with rheumatoid arthritis (RA). METHODS: The literature was searched using the MEDLINE, EMBASE and Cochrane databases. A meta-analysis on the associations between tobacco exposure (TE) and/or SE and the development of anti-CCP antibodies in patients with RA was performed. RESULTS: Eight comparison studies with 5317 RA patients were considered in this meta-analysis. The odds ratio (OR) for positive anti-CCP antibodies in TE+/SE- patients with RA was increased compared with TE-/SE- patients (OR = 1.373, 95% CI = 1.111-1.698, P = 0.003). The ORs for positive anti-CCP antibodies in TE-/SE+ patients and TE+/SE+ patients with RA were also increased compared with TE-/SE- patients (OR = 2.678, 95% CI = 2.031-3.532, P < 1.0 × 1(0-9) in TE-/SE+; OR = 4.233, 95% CI = 2.458-7.291, P = 1.9 × 10(-8) in TE+/SE+). Stratification by ethnicity indicated the same pattern as that shown in the overall group. The OR for positive anti-CCP antibodies in TE+/SE+ patients with RA was much higher than in TE-/SE- patients in Europeans and Asians (OR = 3.879, 95% CI = 2.203-6.830, P = 2.6 × 10(-7); OR = 10.504, 95% CI = 3.182-34.67, P = 1.1 × 10(-4)). CONCLUSIONS: This meta-analysis suggests a gene-environmental interaction between smoking and SE for the development of anti-CCP antibodies.
23653309 Health behaviour change interventions for the promotion of physical activity in rheumatoid 2013 Dec BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease with typical onset between the ages of 40 and 50 years. Increasing levels of physical activity (PA) have been shown to decrease inflammation, reduce pain, increase functional ability and improve self-esteem in people with RA. Health behaviour change (HBC) interventions have recently shown promise in facilitating the promotion of PA within a range of long-term conditions. There is currently no evidence synthesis relating to HBC interventions to increase PA in the RA population. OBJECTIVES: The aim of the present study was to determine whether HBC interventions can increase PA in people with RA and identify optimal interventions or promising constituent components of the HBC interventions. METHODS: A systematic literature search was conducted to identify randomized, controlled trials investigating the effect of HBC interventions on PA level in adults with RA. Four review authors independently assessed the methodological quality of studies and extracted data based upon predefined criteria. RESULTS: Following the application of inclusion/exclusion criteria, three studies remained for inclusion. Two studies reported significant short-term (<9 months) beneficial effects of HBC upon PA (p < 0.05). Individualized interventions were significantly more effective (p < 0.05). CONCLUSIONS: Due to methodological flaws and a lack of comparison with usual care, it is not possible to conclude whether HBC interventions can increase PA in the RA population. Although it is possible to highlight promising elements of HBC interventions, such as goal setting and feedback on performance, further research on all specific components, including information provision, behaviour contracts and problem solving, is required to establish conclusive clinical guidelines.
24151945 Immunogenicity - implications for rheumatoid arthritis treatment. 2013 Biologic agents used to treat rheumatoid arthritis are in- trinsically immunogenic, as they represent complex proteins which are manufactured outside of the recipient of the drug. This is true for chimeric antibodies, humanized antibod- ies, and for fusion proteins. The emergence of antibodies against biologic agents (AAB) will influence both short and long-term efficacy of these agents and may also play a role in adverse events such as infusion reactions. For patients who fail an initial biologic agent or for those who initially respond but lose efficacy, knowledge of whether an AAB is present will allow the clinician to more effectively choose the best agent to which the patient can be switched. The pres- ence of rising ANA titers or antibodies to double stranded DNA may be a good marker for the emergence of AABs. Concurrent use of non-biologic DMARDs at appropriate doses is critical to prevent the evolution of AABs and to ensure long-term efficacy of the biologic agent.
25558613 [Palindromic rheumatism or incipient rheumatoid arthritis--chances of drug therapy]. 2014 A patient suffering from palindromic rheumatism has recurrent periods of pain and swelling of joints lasting for hours, days or maximally 1 to 2 weeks with an irregular pattern.The diagnosis can be made based on patient history and rheumatoid factor or anti-citrullinated peptide antibodies (positive in approx. 50 to 70%) or on the basis of patient history and objectively established joint swelling. Hydroxychloroquine and other ordinary antirheumatic drugs slow down or may even prevent the progression of palindromic rheumatism into chronic rheumatoid arthritis.
24472574 How citrullination invaded rheumatoid arthritis research. 2014 Jan 29 Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium. Here we will discuss the development and importance of anti-citrullinated protein antibodies in rheumatoid arthritis as well as recent findings implicating citrullination in the pathophysiology of rheumatoid arthritis.
24637364 Rheumatoid arthritis: treating cardiovascular risk in RA requires multidisciplinary care. 2014 Apr Rheumatoid arthritis is associated with an excess risk of cardiovascular disease, but current cardiovascular risk models might not be adequate to fully predict individual risk in a patient with this disease. Does the solution lie in closer collaboration between rheumatologists and cardiologists?