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ID PMID Title PublicationDate abstract
21427581 Update 2011: leflunomide in rheumatoid arthritis - strengths and weaknesses. 2011 May PURPOSE OF REVIEW: Leflunomide is often used as a first choice disease-modifying antirheumatic drug after methotrexate. New data are available for efficacy and safety in both, monotherapy and combination with biologicals. RECENT FINDINGS: New data on efficacy demonstrate comparable effect sizes for leflunomide and methotrexate in the treatment of signs and symptoms in combination with tumour necrosis factor-blocking agents and rituximab. Equipotency has also been demonstrated by a recent radiographic outcome study on methotrexate and leflunomide monotherapy. Pharmacogenetic studies indicate an impact of polymorphisms on the variability in serum levels of the compound with potential relevance to effectiveness and tolerability in individual patients. Genetic factors are also likely to contribute to the significantly increased risk for leflunomide-induced pulmonary disease reported in Asia. Because pre-existing interstitial lung disease as well as methotrexate-induced pneumonitis have been identified as risk factors for leflunomide-induced pulmonary disease, the use of leflunomide as an alternative to methotrexate is limited under these conditions. SUMMARY: Effectiveness of leflunomide renders it a potent treatment option in rheumatoid arthritis. The known tolerability issues resulting in a less favourable adherence to therapy constitutes a weakness. However, documented data from large registries indicate that leflunomide is safe as far as the contraindications and recommendations for monitoring are regarded.
20980286 Urinary type II collagen C-terminal peptide is associated with synovitis and predicts stru 2011 Feb OBJECTIVES: In rheumatoid arthritis, high levels of the cartilage turnover biomarker C-terminal cross-linking telopeptide of type II collagen (CTX-II) predict an increased risk of radiological progression. In very early inflammatory arthritis erosions are uncommon, therefore CTX-II requires validation against early markers of inflammatory arthritis such as power Doppler ultrasound (PDUS) synovitis and bone mineral density (BMD) loss. METHODS: In 50 subjects with 12 weeks or less of inflammatory hand symptoms, urinary CTX-II and PDUS were performed at baseline and hand BMD at baseline and 12 months. CTX-II data were log transformed to a normal distribution. Associations between variables were examined using Pearson's r/Spearman's ρ correlations. RESULTS: The mean 12- month change in BMD was -0.0068 g/cm² and the geometric mean for baseline CTX-II/creatinine was 245.89 ng/mmol. Log-transformed baseline CTX-II showed a substantive negative association with change in average BMD over 12 months, controlling for baseline BMD and erythrocyte sedimentation rate (r=-0.359, p=0.044). The median total PDUS score was 3.0 and baseline CTX-II was significantly associated with baseline total PDUS (Spearman's ρ=0.482, p=0.002). CONCLUSION: Urinary CTX-II correlates with PDUS synovitis and hand BMD reduction very early in the course of inflammatory arthritis, suggesting that CTX-II has potential as a biomarker in very early inflammatory arthritis.
22878927 Analysis of direct medical and nonmedical costs for care of rheumatoid arthritis patients 2013 Jul OBJECTIVES: Our goal was to determine the annual direct medical and nonmedical costs for the care of patients with rheumatoid arthritis (RA) using data from a large cohort database in Japan. METHODS: Direct medical costs [out of pocket to hospitals and pharmacies and for complementary and alternative medicine (CAM)] and nonmedical costs (caregiving, transportation, self-help devices, house modifications) were determined for RA patients who were participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) studies conducted in October 2007 and April 2008. Correlations between these costs and RA disease activity, disability level, and quality of life (QOL) were assessed. RESULTS: Data were analyzed from 5,204 and 5,265 RA patients in October 2007 and April 2008, respectively. The annual direct medical costs were JPY132,000 [out of pocket to hospital (US$1 = JPY90 in 2007)], JPY84,000 (out of pocket to pharmacy), and JPY146,000 (CAM). Annual direct nonmedical costs were JPY105,000 (caregiving), JPY22,000 (transportation), JPY30,000 (self-help devices), and JPY188,000 (house modifications). Based on the utilization rate for each cost component, the annual medical and nonmedical costs for each RA patient were JPY262,136 and JPY61,441, respectively. Costs increased with increasing RA disease activity and disability level or worsening quality of life (QOL). CONCLUSIONS: Based on the IORRA database, patients with RA bear heavy economic burdens that increase as the disease is exacerbated. The results also suggest that the increase in medical and nonmedical costs may be ameliorated by the proactive control of disease activity.
21097799 Clinical and ultrasonographic remission determines different chances of relapse in early a 2011 Jan OBJECTIVES: Treatment of rheumatoid arthritis (RA) should aim at full remission. The aims of this study were to define: (1) how many patients reached ultrasound power Doppler (US-PD) remission in a cohort of patients with early RA (ERA) compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission; and (3) how many patients with and without US-PD remission relapsed after 1 year of follow-up in ERA and LSRA. METHODS: 48 patients with ERA and 46 with LSRA with disease activity score <1.6 underwent US assessment. Six hand and wrist joints were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those with LSRA fulfilled American College of Rheumatology (ACR) remission criteria. RESULTS: 43.7% of patients with ERA and 17.4% of those with LSRA had no evidence of synovitis at US evaluation. Using a stricter clinical definition of remission (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of patients with ERA and 26.1% of those with LSRA. Early disease was predictive of clinical US remission. 20.0% of patients with RA who had a negative PD signal at the US evaluation had a flare during the 12-month follow-up period compared with 47.1% of patients who had a positive PD signal. CONCLUSION: US-PD remission occurs in half of patients with ERA and in a minority of patients with LSRA in clinical remission. Early disease seems to be the major determinant of full remission.
22459642 The role of ultrasonography in early detection and monitoring of shoulder erosions, and di 2012 Jun OBJECTIVES: To determine the accuracy of ultrasound in early detection of bone erosions and monitoring disease activity in rheumatoid arthritis (RA) patients using magnetic resonance imaging (MRI) as a gold standard technique. MATERIAL AND METHODS: This prospective study was carried out on 50 patients with known RA and 15 healthy controls. Conventional radiography was standardized and performed in two planes. Ultrasound (US) and MRI was performed to evaluate the presence of synovitis, tenosynovitis, and bursitis as well as erosions on ultrasound and MRI. The results in the study group were compared with those obtained in a control group. RESULT: In the study group, the most frequent US finding of shoulder joint was Tenosynovitis of the long head of the biceps tendon. Tenosynovitis was observed in the long head of biceps tendon in 20 joints (40%). Erosions of the humeroscapular joint were detected by conventional radiography in 15 (30%), by US in 41 (82%), and by MRI in 46 (92%) of the shoulders examined, no statistically significant difference is noted between US and MRI in overall detection of erosion (P = .333). CONCLUSION: US is a helpful imaging method and in comparison with MRI in assessing the shoulder joint and, preferably with MRI, are recommended as additional techniques in the initial diagnostic evaluation when radiography yields negative results.
22410368 Incomplete thymic involution in systemic sclerosis and rheumatoid arthritis. 2013 Jan OBJECTIVE: The thymus plays a crucial role in immune system homeostasis. Thymic abnormalities have been reported in many autoimmune diseases, but data for systemic sclerosis (SSc) and rheumatoid arthritis (RA) are sparse. The aim of this study was to evaluate the prevalence and correlates of radiological incomplete involution of the thymus in SSc and RA patients, and in a non-autoimmune group of controls. METHODS: All patients were at least 40 years old: 96 SSc patients (median age 59 years, 80% women) and 65 RA patients (median age 57 years, 88% women) were compared with 32 control individuals (median age 63 years, 62% women). Pulmonary CT-scans performed for lung assessment were available for all individuals. For the purpose of our study, complete involution of the thymus was defined as the absence of a residual thymus or a gland thickness, corresponding to the short axis on the axial slice, of less than 7 mm. We defined incomplete involution of the thymus as a residual thymic tissue more than 7 mm thick. RESULTS: The frequency of incomplete thymus involution was significantly higher in SSc and RA patients (respectively 15 and 14%) than in the control group (0%; P<0.05). Incomplete thymus involution was associated with pulmonary restrictive syndrome in SSc patients, and with biotherapy and an absence of antinuclear antibodies in RA patients. CONCLUSION: Our findings show that two autoimmune diseases, SSc and RA, are associated with incomplete thymus involution.
22422494 Smoking, smoking cessation, and disease activity in a large cohort of patients with rheuma 2012 May OBJECTIVE: While cigarette smoking is the best-studied environmental factor contributing to rheumatoid arthritis (RA), no study to date has examined the influence of smoking cessation on disease activity. We examined this relationship in an observational cohort of patients with RA in the United States. METHODS: Patients enrolled in the Consortium of Rheumatology Researchers of North America registry (CORRONA) were stratified into never, former, and current smokers at enrollment. Current smokers were further stratified into continued and ceased smoking groups during their followup in the registry. The primary outcome was change in Clinical Disease Activity Index (CDAI) at last visit in a multivariate, random-effects regression model accounting for multiple timepoints. RESULTS: At last visit, there was no significant change in CDAI between ceased smokers and continued smokers (coefficient -0.00091, SE 0.0033, p = 0.7834). The study did confirm prior cross-sectional studies that current smokers have worse disease activity than former or never smokers. CONCLUSION: In the short term, smoking cessation did not appear to influence change in disease activity over time.
22374112 Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheum 2013 Jan OBJECTIVE: The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined. METHODS: The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls. RESULTS: The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints. CONCLUSION: ImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.
22293762 Hypoxia--a key regulator of angiogenesis and inflammation in rheumatoid arthritis. 2012 Jan 31 The importance of inflammation in rheumatoid arthritis (RA) is well understood. This knowledge has resulted in the development of anti-inflammatory therapies--either broadly acting (such as steroids) or more specific approaches (such as antibodies against TNF)--with biologic therapies (including TNF inhibitors) revolutionizing the treatment of RA. However, what is less well appreciated in RA are the links between inflammation, blood-vessel formation (angiogenesis) and cellular responses to changes in oxygen tension. Inadequate oxygenation, termed hypoxia, is thought to drive the increase in synovial angiogenesis that occurs in RA, through expression of hypoxia-inducible molecules, including vascular endothelial growth factor (VEGF). This process promotes further infiltration of inflammatory cells and production of inflammatory mediators, perpetuating synovitis. This Review highlights the molecular pathways activated by hypoxia, and how these pathways might interact with inflammatory signaling to promote and maintain synovitis in RA, with a particular focus on the response of macrophages to hypoxia in the context of RA. Successful treatment of RA, for example with anti-TNF antibodies, reduces levels of proangiogenic factors, including VEGF, and leads to normalization of the vasculature. These processes emphasise the close links between hypoxia, angiogenesis and inflammation in this disease and supports the concept that angiogenesis blockade could be of therapeutic benefit in RA.
21752873 Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthriti 2011 Oct OBJECTIVES: To evaluate the effectiveness and safety of tocilizumab in RA patients in clinical practice. METHODS: We observed 232 consecutive RA patients who began tocilizumab in three rheumatology centres in Japan for 52 weeks. Clinical, radiographic and functional status and safety were evaluated. RESULTS: Mean age of the 232 patients was 59.1 years, mean duration of disease was 12.4 years and average DAS using the 28-joint count (DAS-28) was 5.6. Although 62.8% of the patients had been treated previously with anti-TNF biologics, clinical remission at Week 52 was achieved in 43.7%, radiographic non-progression in 62.8% and functional remission in 26.4%. Retention rate at Week 52 was 71.1%, and the same for those with or without previous anti-TNF treatment. Adverse drug reactions leading to tocilizumab discontinuation were observed in 15.5% of patients, the most frequent adverse drug reaction being pneumonia in eight cases. On multivariate logistic regression analysis, DAS-28, HAQ-disability index (HAQ-DI), concomitant MTX and concomitant glucocorticoids (GCs) were predictive variables for clinical remission at Week 52 of tocilizumab treatment. In particular, HAQ-DI was found to be a predictive variable for remission of all three types-clinical, radiographic and functional-at Week 52 of tocilizumab treatment. CONCLUSIONS: In daily clinical practice, tocilizumab exhibited excellent effectiveness in established RA patients, some of whom had failed to respond to previous anti-TNF treatment. Although further detailed safety findings are required, this study provides valuable real-world findings on the management of RA with tocilizumab.
21773716 Salivary immunoglobulin A in rheumatoid arthritis (RA) with focus on dental caries: a cros 2012 Feb Salivary secretory immunoglobulin A (sIgA) is postulated to protect against dental caries. Dental hygiene and health are usually poor in rheumatoid arthritis (RA) due to several factors. We hypothesized higher salivary sIgA in caries-free subjects and a higher extent of caries in RA. A protocol-driven cross-sectional pilot study was carried out to determine salivary sIgA in 48 patients with RA and 102 non-RA, healthy case controls. Standard of care in clinical and dental assessments were done by experts. A decay, missing teeth, filled teeth (DMFT) index was used to classify caries. Whole unstimulated saliva was collected to assay sIgA using a commercial ELISA kit. Dental caries was diagnosed in 67% and 86% of the RA and healthy subjects, respectively. Eight percent of RA patients had visited a dental surgeon. Though they tend to be higher in caries-free status, there were no statistically significant differences (p > 0.05) between RA and non-RA subjects with respect to salivary sIgA and extent of caries. The salivary sIgA levels for both RA and healthy case control subjects in this ethnic Indian (Asian) study were much higher than that reported in literature and need further validation. Rheumatologists ought to educate patients on dental matters.
21556860 Genetics of rheumatoid arthritis: what have we learned? 2011 Aug Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 0.5-1% of the population worldwide. The disease has a heterogeneous character, including clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although the pathogenesis of RA is poorly understood, progress has been made in identifying genetic factors that contribute to the disease. The most important genetic risk factor for RA is found in the human leukocyte antigen (HLA) locus. In particular, the HLA molecules carrying the amino acid sequence QKRAA, QRRAA, or RRRAA at positions 70-74 of the DRβ1 chain are associated with the disease. The HLA molecules carrying these "shared epitope" sequences only predispose for ACPA-positive disease. More than two decades after the discovery of HLA-DRB1 as a genetic risk factor, the second genetic risk factor for RA was identified in 2003. The introduction of new techniques, such as methods to perform genome-wide association has led to the identification of more than 20 additional genetic risk factors within the last 4 years, with most of these factors being located near genes implicated in immunological pathways. These findings underscore the role of the immune system in RA pathogenesis and may provide valuable insight into the specific pathways that cause RA.
22293763 The influence of ACPA status and characteristics on the course of RA. 2012 Jan 31 Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, and affects 0.5-1% of the population. Although it poses a considerable health problem, relatively little remains known about the disease pathogenesis and etiology. In the past decade, anti-citrullinated protein antibodies (ACPA) have emerged as suspects in the development and/or progression of RA. Citrullinated proteins--containing the amino acid citrulline, generated post-translationally from arginine--are found in the joints of patients with RA, but are not specific for the disease. This situation contrasts with the presence of ACPA, which are mostly found in individuals with RA. Intriguingly, ACPA can also be found in individuals before symptom onset. In these instances the ACPA response seems to be in its infancy, recognizing only a few citrullinated antigens and not using the full isotype repertoire. These characteristics of the ACPA response mature before clinical disease precipitates. Evidence is emerging that ACPA status can further characterize the heterogeneous RA phenotype, not only with respect to outcome, but perhaps also with respect to intervention. This Review summarizes the evolution of the ACPA response and its putative role in disease pathogenesis, as well as its relationship with clinical phenotype and diagnostic potential.
20450381 Development and psychometric properties of a joint protection self-efficacy scale. 2011 Jun INTRODUCTION: Self-efficacy is one of the most powerful determinants of behaviour change. To increase effectiveness of joint protection (JP) education, it may be important to address perceptions of JP self-efficacy directly. The aim of this study was to develop a scale to measure JP self-efficacy (JP-SES) in people with rheumatoid arthritis (RA). METHODS: Instrument development included item generation, construct validity, and reliability testing. Rasch analysis was applied to determine construct validity and the revised JP-SES was tested again to confirm validity and establish test-retest reliability and internal consistency. RESULTS: A total of 46 items were generated by literature review, occupational therapists, and people with RA. After semi-structured interviews and field-testing with RA participants, a 26-item questionnaire draft was constructed and tested. Rasch analysis to determine construct validity reduced the JP-SES to 13 items with good overall fit values. Rasch analysis of confirmatory validity resulted in a final 10-item version of the JP-SES. Test-retest results supported the validity of the scale, with high internal consistency (α = 0.92) and good test-retest reliability (r(s) = 0.79; p < 0.001). CONCLUSIONS: The JP-SES is a valid and reliable scale to assess perceived ability of people with RA to apply JP methods. The JP-SES could help stimulate the use of efficacy-enhancing methods in JP education.
23093721 Who are the patients with early arthritis with worse than death scores on the EQ-5D? Resul 2013 May OBJECTIVES: The EQ-5D is a five-dimension multi-attribute questionnaire widely used to calculate quality-adjusted life-year scores. We aimed to describe patients with early arthritis (EA) and EQ-5D < 0, a state worse than death, at baseline and over 2 years and determine aspects of EA associated with a negative score. METHODS: EQ-5D scores for 813 patients were longitudinally assessed over 24 months. Characteristics and health status of patients with EQ-5D < 0 were analysed. Multivariate logistic regression was used to determine aspects of EA associated with a negative score. RESULTS: At baseline, 90 (11%) patients had a negative EQ-5D score (median EQ-5D -0.052; range -0.530 to -0.011). Almost all patients had extreme pain/discomfort and at least moderate problems in anxiety/depression domain. These patients had lower educational level, greater disease activity, higher HAQ score (greater functional disability), greater pain and fatigue, lower Short Form 36 (SF-36) mental component scores and higher CRP levels than patients with EQ-5D ≥ 0 (all P < 0.001). In the logistic regression model, worse HAQ and SF-36 mental component scores were associated with EQ-5D < 0. Results were similar at 6, 12 and 24 months, with 25, 23 and 24 patients, respectively, in a state worse than death. CONCLUSION: Pain or discomfort, often severe, is a key domain of the EQ-5D for patients with EA in a health state worse than death, and poor HAQ and SF-36 mental component scores were always independently associated with a state worse than death. EA patients may have specific needs necessitating better management of pain and psychological state.
21125298 Surgical treatment for atlantooccipital osteoarthritis: a case report of two patients. 2011 Jul BACKGROUND/PURPOSE: Although rarely discussed in the literature and difficult to evaluate on plain radiographs, atlantooccipital osteoarthritis can be a source of persistent suboccipital pain. Our objective in this report is to describe two cases with atlantooccipital (O-C1) osteoarthritis treated with posterior occipitocervical fusion. METHODS AND RESULTS: Two patients presented with unilateral suboccipital pain, which was refractory to conservative treatment. One patient suffered from long-standing rheumatoid arthritis while the other patient did not have pertinent medical issues. After non-diagnostic plain film imaging, CT scan demonstrated unilateral osteoarthritis of the atlantooccipital and atlantoaxial joint in both patients who subsequently underwent posterior O-C2 fusion with resolution of their preoperative symptoms. CONCLUSIONS: This is, to our knowledge, the first case report which specifically focused on surgical treatment of atlantooccipital osteoarthritis. Occipitocervical fusion is a treatment option for patients with atlantooccipital osteoarthritis when suboccipital pain is not responsive to conservative treatment.
21115551 A decrease in disease activity score (DAS) level is associated with a decrease in health a 2011 Jan OBJECTIVE: To assess the relationship between a decrease in disease activity score (DAS) and functional ability during 5 years of DAS-steered treatment in recent-onset rheumatoid arthritis (RA) patients, taking into account absolute DAS levels and follow-up duration. METHODS: Data from the BeSt study were used, in which treatment was aimed at achieving DAS ≤2.4. The longitudinal relationship between 3-monthly measured DAS and health assessment questionnaire (HAQ) score was assessed using linear mixed modelling during 5 years of treatment, with DAS and HAQ 3 months earlier, change in DAS in last 3 months (delta DAS), time (log-transformed) and their interactions as determinants. RESULTS: Predictors for HAQ were: previous DAS, delta DAS, ln time, the interaction previous DAS×delta DAS, and previous HAQ. The interaction ln time×delta DAS was non-significant, indicating that the association between delta DAS and HAQ was independent of follow-up duration. A decrease from a higher DAS was associated with a smaller HAQ decrease than for a similar decrease from a lower DAS, indicating a non-linear relationship between DAS and HAQ. CONCLUSION: At any time during 5 years of follow-up, a decrease in DAS was associated with a better functional ability. The magnitude of HAQ improvement depends on the DAS decrease and on the absolute DAS level.
21344966 Circumferential encasement of the spinal cord in a patient with rheumatoid arthritis. 2011 Apr Myelopathy associated with rheumatoid arthritis (RA) usually involves the craniocervical junction or mid-cervical spine. We present an unusual case of an encasing circumferential inflammatory mass at the cervico-thoracic junction down to the mid-thoracic spine. The need to consider inflammatory lesions even in unusual anatomical locations in patients with RA is illustrated.
22446003 [Suppurative arthritis caused by Gemella morbillorum in a patient with rheumatoid arthriti 2012 Mar Rheumatoid arthritis of the knee is a common disease, but suppurative arthritis caused by Gemella morbillorum in the same joint is rare. We report a case of suppurative arthritis caused by Gemella morbillorum in a patient with rheumatoid arthritis. Because the infection symptoms was not typical, the diagnosis was delayed, and the delayed diagnosis and therapy led to a poor outcome of the patient.
22864134 Sitagliptin (DPP-4 inhibitor)-induced rheumatoid arthritis in type 2 diabetes mellitus: a 2012 A dipeptidyl peptidase (DPP)-4 inhibitor, commonly used to treat patients with type 2 diabetes, has caused concern because of immune system side effects. We report a 48-year-old woman with type 2 diabetes who was diagnosed with rheumatoid arthritis (RA) after continued polyarthritis and an increase in rheumatoid factor up to 86 IU/mL after three months of treatment with sitagliptin, a DPP-4 inhibitor. The shared epitope (SE)-containing human leukocyte antigen (HLA)-DRB1 alleles, which are important predisposing factors for RA, were positive. RA might have been triggered by sitagliptin due to a predisposing condition.