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ID PMID Title PublicationDate abstract
19082778 Comparison of osteoclast precursors in peripheral blood mononuclear cells from rheumatoid 2009 Osteolytic disorders cause serious problems for quality of life with aging. Osteolysis is performed by osteoclasts of the hematopoietic lineage that share some characteristics with monocytes and macrophages. As osteoclast precursors (pOCs) are present in peripheral blood, their characterization in osteolytic diseases may help us to understand risk factors. Although essential factors for osteoclastogenesis have been reported, the effective induction from pOCs in human peripheral blood mononuclear cells (PBMCs) to mature osteoclasts in culture requires further improvement. The aim of this study was development of an efficient culture system for human osteoclastogenesis and providing a simple system for the enrichment of pOCs from PBMCs. We employed coculturing of human PBMCs with a mouse stromal cell line. Significant numbers of tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated osteoclasts (MNCs), which could resorb dentine slices, were efficiently induced in this culture condition. pOCs were enriched in an anti-CD16 antibody column-passed anti-CD14 antibody-bound cell population isolated by magnetic cell sorting. We compared the percentage of the CD14(high) CD16(dull) cell population, which mainly contained pOCs in PBMCs, from age-matched patients with rheumatoid arthritis (RA) and osteoporosis (OP), but it was comparable. However, the mean number of TRAP(+) MNCs generated in cultures from PBMCs of RA was higher. In contrast, the frequency of pOCs in PBMCs from OP was relatively higher. These results suggest the characteristics of pOCs from RA and OP may be different, because single pOCs from OP gave rise to lower numbers of osteoclasts than those from RA.
18317768 Physical activity prevents bone loss in premenopausal women with rheumatoid arthritis: a c 2008 Aug The aim of the study was to compare the bone loss and the influence of physical activity between premenopausal women with rheumatoid arthritis (RA) and healthy women. A total of 71 patients with RA and 29 healthy premenopausal women with the criteria of the American College of Rheumatology for RA were followed for 2 years. Of these 85% were Caucasian, aged 38 +/- 6.6 years and with a duration of disease of 88 +/- 50 months and 48 (71.8%) used GC, mean daily dose, 7.3 +/- 3.5 mg. There was a reduction in the T-score of the femoral neck (P = 0.04) and in the Ward region (P = 0.05) in RA. Through logistic regression, it was found that sedentarism was a risk factor for osteopenia in RA, with relative risk of 1.6 (IC = 1.238-1.734). Moderate physical activity reduced the risk of osteopenia by 50%. Sedentarism and low weight are the main factors associated with bone loss. Physical activity reduces bone loss. Early preventive and therapeutic measures must be encouraged.
17071051 The use of low dose methotrexate in rheumatoid arthritis - are we entering a new era of th 2006 Dec Methotrexate (MTX) is one of the most commonly used medications in the treatment of rheumatoid arthritis (RA). It has proven efficacy as a sole agent as well as in combination with other disease modifying anti-rheumatic agents (DMARDs) including the newer biological agents. MTX is generally well tolerated although there are a number of potentially serious adverse effects. Of these, haematopoietic suppression, hepatotoxicity and pulmonary toxicity are the more severe and patients are therefore required to have appropriate monitoring while they remain on MTX. In the past, attempts at therapeutic drug monitoring using serum MTX concentrations have been unsuccessful. However, MTX is taken into red blood cells (RBC) where up to four glutamates are added to form MTX polyglutamates (MTXPG(n)). More recently it has been suggested that higher RBC MTXPG(3-5) concentrations may be associated with improved disease control. Genetic variations in enzymes involved in the uptake of MTX into cells and its metabolism are also being examined for their ability to predict drug response and potential for adverse events. While it is unlikely that a single genetic variant will predict efficacy or toxicity there is preliminary evidence that a "pharmacogenetic index" that takes into account the effects of multiple genetic variants maybe useful. Although in their infancy at present, both therapeutic drug monitoring using MTXPG concentrations and pharmacogenomics of MTX may prove useful in the future and are worthy of further investigation.
16950363 Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid arthritis: a 2006 Sep 2 BACKGROUND: Chaperonin 10 (heat shock protein 10, XToll) has anti-inflammatory properties related to the inhibition of Toll-like receptor signalling pathways. Our aim was to establish whether chaperonin 10 is safe and effective in the treatment of rheumatoid arthritis. METHODS: In this randomised, double-blind, multicentre study, 23 patients with moderate to severe active rheumatoid arthritis receiving disease-modifying antirheumatic drugs were randomly allocated to three treatment groups receiving intravenous chaperonin 10 twice weekly for 12 weeks at doses of 5 mg (n=8), 7.5 mg (8), or 10 mg (7). The primary outcomes were change in disease activity score (DAS28) and improvement of core disease measures (American College of Rheumatology response score) from baseline to week 12. All analyses were done by intention to treat. This study is registered with the Australian Clinical Trials Registry, number ACTRNO12606000041550. FINDINGS: Primary endpoint measures improved from day 14 in all groups and continued to improve to day 84. By end of study, a 20% improvement of core disease measures was seen in six (86%, 95% CI 43-100), a 50% improvement in four (57%, 14-86), and a 70% improvement in two (29%, 0-57) patients given the highest dose of chaperonin 10. Clinical remission (as defined by a DAS28 <2.6) was achieved in three (13%) of 23 patients. Three individuals dropped out during the study: one in the 5 mg group (rheumatoid arthritis not controlled), one in the 7.5 mg group (adverse event), and one in the 10 mg group (lost to follow-up). The most common adverse events were exacerbation of rheumatoid arthritis (both during and after the study) and upper respiratory tract infection. Only one adverse event was judged to be of severe intensity. INTERPRETATION: Chaperonin 10 seems to be well tolerated and efficacious in treatment of the symptoms of rheumatoid arthritis, at least in the short term.
16707531 Asporin repeat polymorphism in rheumatoid arthritis. 2007 Jan BACKGROUND: Asporin belongs to a family of proteins associated with the cartilage matrix. OBJECTIVE: To investigate the role of the functional polymorphism consisting of an aspartic acid (D) repeat polymorphism located in the ASPN gene in the susceptibility to and clinical outcome of rheumatoid arthritis. METHODS: A total of 803 Spanish Caucasian patients with rheumatoid arthritis and 904 controls of the same ethnic origin and matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped using polymerase chain reaction with a fluorescent primer. RESULTS: No significant differences were detected in the distribution of the 10 alleles found in our population on comparing patients with rheumatoid arthritis with control groups. Nevertheless, individuals bearing D14 produced rheumatoid factor more often than the rest (85.7% v 72.1%, p = 0.006, odds ratio (OR) = 2.35, 95% confidence interval 1.21 to 4.50), and the mean (SD) onset age was higher in the group of individuals bearing D13 (50.09 (13.94)) compared with the rest (47.21 (14.31)), although the difference did not reach significance (p = 0.06). CONCLUSION: The results do not support a major role for asporin D repeat polymorphism in the susceptibility to rheumatoid arthritis. Nevertheless, they support the influence of this gene on the outcome of the disease.
18784629 High mortality rate in rheumatoid arthritis with subluxation of the cervical spine: a coho 2008 Oct 1 STUDY DESIGN: In a prospective cohort study 532 patients with rheumatoid arthritis (RA) and subluxations of the cervical spine were consecutively collected during 1974-1999. OBJECTIVE: The aims of the study were to assess important factors affecting the mortality rate and the timing of surgical intervention. SUMMARY OF BACKGROUND DATA: The average follow-up time from the first visit to death or to the end of the study was 8.5 (SD, 5.7) years. Of the 217 operated patients 144 (66%) died, and of the 315 nonoperated patients 137 (43%) died. METHODS: Patients were selected for operative intervention based on anterior, vertical and subaxial subluxations, pain, and/or cervical neurology. Survival analyses were used for comparisons between patients with RA and the normal population, and between the operated and those treated conservatively. RESULTS: The survival rate for all RA patients was significantly reduced when compared with average survival in Norway (P < 0.001). The operated group had a significantly lower survival rate than the nonoperated group. In patients with severe instability of the cervical spine, the defined selection criteria for surgical intervention were specific. By comparison of calculated propensity scores, the operated and nonoperated groups were too different to be directly comparable. After surgery only 11 patients (5%) experienced residual pain in the neck or neurologic symptoms. None of these patients were alive at the end of the study, signifying that residual pain or neurologic symptoms are poor prognostic signs (P = 0.015). In the operated group, anterior subluxation and vertical settling greater than the lower indication limits did not have a significant influence on the survival rate, but there was a reduced survival for patients with subaxial subluxations. A clear association was found between increased vertical settling and sudden death. CONCLUSION: RA with neck involvement is a progressive and serious condition with reduced lifetime expectancy. Hence, our interpretation is that operative intervention improves local symptoms and most likely changes the condition from worse to better by increasing lifetime expectancy in high risk patients. Since the per- and postoperative complications are few, a changed attitude toward more liberal indications for earlier surgery may reduce the symptoms and the mortality rate even more.
16670155 Bone oedema predicts erosive progression on wrist MRI in early RA--a 2-yr observational MR 2006 Dec OBJECTIVES: To investigate if disease assessment by contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative nanocolloid (NC) scintigraphy gives useful additional information in early rheumatoid arthritis (RA). METHODS: Twenty-seven patients with early RA (disease duration < or =12 months) were followed up for 1 yr and 24 of them for 2 yrs with contrast-enhanced MRI and NC scintigraphy of the wrist joint. Synovial inflammation was assessed by measuring time-dependent enhancement rates (E-rate) from dynamic MRI scans and technetium(99m)-labelled nanocolloid ((99m)Tc-NC) uptake from scintigraphy scans. Synovial membrane hypertrophy, bone oedema and erosions were semiquantitatively scored according to the Outcome Measures in Rheumatology Clinical Trials RA-MRI scoring system from static MR images. Response to the treatment was evaluated based on whether or not > or = 50% improvement was achieved in the tender and swollen joint scores and the Health Assessment Questionnaire score, with normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) levels. Progression of the erosion score on wrist MRI was evaluated as the outcome. RESULTS: The baseline MRI bone oedema score (rho= 0.67), MRI synovitis score (rho= 0.57), ESR (rho= 0.56), CRP (rho= 0.48), E-rate (rho= 0.47) and (99m)Tc-NC uptake (rho= 0.45) were related with the change in the MRI erosion score from baseline to 2 yrs (rho= Spearman's correlation). In the multivariate logistic regression model, the bone marrow oedema score was the only baseline variable that predicted erosive progression at 2 yrs' follow-up (OR 4.2, 95% CI 1.3-13.8). The median (interquartile range) change in the erosion score from baseline to 2 yrs was 0 (0, 0) and 4 (2, 5) in the patients with (n= 9) and without (n= 15) a persistent clinical response over the 2 yrs, respectively (P= 0.001). The non-responders who presented with erosive progression from 1 yr to 2 yrs had higher MRI synovitis scores, bone oedema scores, E-rate and (99m)Tc-NC uptake at 1-yr follow-up than the non-responders without progressive bone damage. CONCLUSION: The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.
16793624 [Long-term follow-up results of synovectomy for rheumatoid knee]. 2006 Jun OBJECTIVE: To continuously observe the long-term effects of synovectomy for improving joint damage and quality-of-life in patients with the rheumatoid knee. METHODS: Twenty-one consecutive patients with rheumatoid arthritis (RA) involving 24 knees underwent open synovectomy from November 1988 to January 1997 between November 1988 and January 1997. The changes in radiographic damage were assessed with Larsen score on plain films before and 6 months after surgery with subsequent annual assessment for 8 years, and the functional recovery of the patients was also evaluated with Health Assessment Questionnaire (HAQ) at the same time. RESULTS: The radiographic joint damage and juxta-articular osteoporosis or bone erosion was ameliorated after surgery in all the patients. Larsen score began to decrease 6 months after the operation, and the best effects were achieved at one year and maintained for at least 5 years after the operation, but then followed by recurrence of joint lesions. HAQ scores were improved after the surgery with the best effects observed 6 months after the operation lasting for over 2 years. HAQ score gradually decreased 4 years after the operation till reaching the preoperative scores. CONCLUSION: Synovectomy in the patients with rheumatoid knee not only reverses progressive joint damage, but also improves juxta-articular bone erosions and the patients' quality of life. However, radiographic joint damage and functional deterioration may recur due to hyperplasia of the inflammatory synovium in the long term after operation, suggesting that the inflammatory synovium participates in local joint damage with bone erosions and systemic pathologic process of RA.
16690763 Prevalence and management of rheumatoid arthritis in the general population of Greece--the 2006 Dec OBJECTIVE: To assess the prevalence and management of rheumatoid arthritis (RA) in the general adult population of Greece. METHODS: This cross-sectional study was conducted on the total adult population (> or =19 yrs old) of seven communities (8,547 subjects), and on 2,100 out of 5,686 randomly selected subjects in two additional communities. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Diagnosis of RA was based on the American College of Rheumatology (ACR) 1987 criteria. RESULTS: A total of 8,740 subjects participated (response rate 82.1%). RA was diagnosed in 59 individuals. The prevalence of RA was 0.68% (95% CI 0.51-0.85); it was significantly higher in females than males (P< 0.0005), and increased significantly with age up to and including the 50-59-yr-old group (P< 0.002), and then decreased slightly. On their first medical visit, 19% (95% CI 9.7-30.9) of the RA patients had consulted a rheumatologist, while during the first year after disease onset, 61% (95% CI 48.6-73.4) had done so. Early consultation with a rheumatologist and disease-modifying anti-rheumatic drug (DMARD) combination therapy were negatively associated with ACR functional classes II-IV [adjusted odds ratios 0.18 (95% CI 0.04-0.85) and 0.17 (95% CI 0.04-0.72), respectively]. CONCLUSIONS: The prevalence of RA in the general adult population of Greece is similar to that in many other European countries; early consultation with a rheumatologist and DMARD combination therapy are associated with a better RA outcome.
18801760 Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analy 2009 Jul OBJECTIVE: The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. METHODS: 768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated with methotrexate, were included. Hand bone loss was assessed by digital x ray radiogrammetry (DXR) on the same hand radiographs scored with modified Sharp score at baseline, 26, 52 and 104 weeks. For DXR, metacarpal cortical index (MCI) was the primary bone measure. RESULTS: At all time points the rate of percentage DXR-MCI loss was lowest in the combination group (-1.15; -2.16; -3.03) and greatest in the methotrexate monotherapy group (-1.42; -2.87; -4.62), with figures in between for the adalimumab monotherapy group (-1.33; -2.45; -4.03). Significant differences between the combination group and the methotrexate group were seen at 52 (p = 0.009) and 104 weeks (p<0.001). The order of hand bone loss across the three treatment arms was similar to the order of radiographic progression. Older age, elevated C-reactive protein and non-use of adalimumab were predictors of hand bone loss. CONCLUSION: This study supports a similar pathogenic mechanism for hand bone loss and erosions in RA. The combination of adalimumab and methotrexate seems to arrest hand bone loss less effectively than radiographic joint damage. Quantitative measures of osteoporosis may thus be a more sensitive tool for assessment of inflammatory bone involvement in RA.
18057668 [Secondary osteoporosis. Bisphosphonates as a possible strategy for the prevention of bone 2007 Dec Recent studies demonstrated that osteoclastic bone resorption played an important role in joint destruction by rheumatoid synovium. Bisphosphnates inhibit osteoclastic bone resorption and have been widely used for the treatment of osteoporosis. Bisphosphonates, such as zolendronic acid (ZA) inhibited bone destruction in animal models of inflammatory arthritis, although the drug was not effective for the suppression of inflammation. In early RA patients, ZA was effective to prevent bone destruction in combination with methotrexate. Targeting osteoclasts with bisphosphonates is an effective strategy to maintain joint integrity when combined with anti-rheumatic therapy.
18274751 Comparison of the expression profile of apoptosis-associated genes in rheumatoid arthritis 2008 May The purpose of this study was to employ microarray analysis to evaluate differential gene expression in synovial tissue samples obtained from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) to study the expression profile of apoptosis-associated genes in these tissues. Four samples were obtained from RA-affected patients and three from osteoarthritis patients. After total RNA was extracted from synovial tissue, the RNA was processed using two-cycle target labeling, followed by hybridization and scanning procedure. The GeneChip Human Genome U133 Plus 2.0 containing 900471 gene loci was used and eight genes associated with apoptosis were identified with a selected p value<0.05 and a twofold change in expression in rheumatoid samples compared to osteoarthritis tissues. Anti-apoptotic genes were generally upregulated whereas apoptotic genes were downregulated suggesting that these genes may play a role in the pathogenesis of RA. Furthermore, these genes may serve as novel therapeutic targets for the treatment of RA.
19018900 Models based on value and probability in health improve shared decision making. 2008 Oct RATIONALE, AIMS AND OBJECTIVES: Diagnostic reasoning and treatment decisions are a key competence of doctors. A model based on values and probability provides a conceptual framework for clinical judgments and decisions, and also facilitates the integration of clinical and biomedical knowledge into a diagnostic decision. METHOD: Both value and probability are usually estimated values in clinical decision making. Therefore, model assumptions and parameter estimates should be continually assessed against data, and models should be revised accordingly. Introducing parameter estimates for both value and probability, which usually pertain in clinical work, gives the model labelled subjective expected utility. Estimated values and probabilities are involved sequentially for every step in the decision-making process. RESULTS: Introducing decision-analytic modelling gives a more complete picture of variables that influence the decisions carried out by the doctor and the patient. CONCLUSION: A model revised for perceived values and probabilities by both the doctor and the patient could be used as a tool for engaging in a mutual and shared decision-making process in clinical work.
16872514 Environmental risk factors differ between rheumatoid arthritis with and without auto-antib 2006 The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03-2.64, for > 20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22-3.19, for 0 versus > 0-5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07-4.42, for > 10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06-2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54-11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73-6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age > or = 15 years had about twice the risk of either RA subtype compared with women with menarche at age < or = 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.
18084698 The effect of disease activity on fat-free mass and resting energy expenditure in patients 2007 Rheumatoid arthritis (RA) is a chronic joint disease of undetermined cause that is associated with significant disability. Low-grade fever, anemia, and weight loss are recognized extra-articular features associated with increased disease activity. Weight loss and cachexia are well-established features of RA. The mechanism behind weight loss in RA is not known and may be multifactorial. Reduced energy intake and hypermetabolism are the major two factors frequently implicated in the etiology of RA cachexia. One would expect the effect of the above two factors to be highest during increased disease activity and lowest during remission. The purpose of this study was: (a) to establish whether in RA patients changes in body composition mirror changes in disease activity, (b) to investigate the relation between the energy expenditures and weight loss, (c) to examine the dietary energy intake and its role in weight loss in RA patients, and (d) to investigate the relation between the cytokine interleukin (IL)-6 and other variables including resting energy expenditure (REE), body composition, and acute phase reactants. Fourteen patients with RA were age-, sex-, and race-matched with 14 controls from patients with noninflammatory diseases/soft tissue rheumatism. The measurements included the following: disease activity assessment, anthropometric measurements, indirect calorimetry, and measurements of dietary intake. Blood was collected to measure the acute-phase reactants and IL-6 levels. We demonstrated that loss of fat-free mass (FFM) might accelerate during times of increased disease activity and is only partially restored during periods of reduced disease activity. This probably means that the extent of cachexia in RA patients is determined by the frequency and intensity of disease activity (flare) for a given disease duration. Hypermetabolism with increased REE was more evident during increased disease activity. Hypermetabolism in the face of increased energy intake continued to cause loss of the FFM. Interleukin-6 correlates with increased REE and erythrocyte sedimentation rate. There was no direct association between IL-6 level and low FFM. We conclude that loss of FFM is common in RA, cytokine production in RA is associated with altered energy metabolism, and preservation of FFM is important in maintaining good quality of life in patients with RA.
17952483 Etanercept in the treatment of rheumatoid arthritis: clinical follow-up over one year by u 2008 Apr We evaluated clinically and sonographically the effects of etanercept therapy in patients with rheumatoid arthritis (RA) over 12 months of treatment. Eighteen patients affected by RA who were non-responders or partial responders to disease modifying therapy were commenced on Etanercept treatment. Before starting therapy (T0) and at 12 months (T1), the following parameters were evaluated: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS) for pain, number of painful and swollen joints, health assessment questionnaire (HAQ) and disease activity score in 28 joints (DAS 28). Musculoskeletal ultrasound (US) was performed in the following joints: second and fifth metacarpophalangeal, third interphalangeal, wrist and knee joints and a semiquantitative score (0-3) calculated and used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis, bursitis) and/or structural damage (bone erosion and cartilaginous change). An overall score was calculated based on the sum of the single scores to obtain a comprehensive score indicative of the global pathological change. The US global scores significantly reduced between T0 and T1 (p < 0.0001). The following laboratory and clinical parameters also significantly reduced: ESR (p < 0.0001), CRP (p < 0.02), VAS (p < 0.001), number of total swollen joints (p < 0.001), number of total painful joints (p < 0.01), HAQ scores (p < 0.05) and DAS 28 (p < 0.0001). A positive response to treatment with Etanercept was demonstrated both by US examination of several joints and by clinical evaluation of several parameters. US is a useful tool in the monitoring of biologic therapy in RA, assessing both inflammatory and destructive changes.
17644537 Reliability and sensitivity to change of the Simple Erosion Narrowing Score compared with 2008 Mar OBJECTIVE: To compare the performance of a simplified scoring method for structural damage on radiographs of patients with rheumatoid arthritis (the Simple Erosion Narrowing Score or SENS) with the Sharp-van der Heijde Score (SHS) as reference. METHOD: We used the radiographic data from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO trial). The SENS was derived from the crude SHS data. Inter-observer reliability for status scores and change scores was determined by intraclass correlation coefficients and by the Smallest Detectable Change method. The ability to discriminate between treatment groups was assessed by the Mann-Whitney U test. Stratifying the sensitivity to change and discriminative ability for different levels of disease severity assessed a potential ceiling effect. RESULTS: Inter-observer reliability was similar for both methods. Intraclass correlation coefficients were higher for status scores than for change scores. The Smallest Detectable Change was 4.98 (1.1% of possible maximum score) for SHS and 2.28 (3.5%) for SENS. Sensitivity of SENS to detect progression above the Smallest Detectable Change, with reference SHS, ranged from 45.0 to 88.7%. Specificity ranged from 81.5 to 97.3%, and the kappa coefficient (between-method agreement) ranged from 0.58 to 0.66. Discriminative ability between treatment groups was good and similar for both methods. A ceiling effect could not be detected. CONCLUSIONS: With regard to most of the tested properties, the performance of SENS is as good as that of SHS. This confirms that SENS is a valuable method, which may be feasible in clinical practice.
16821265 SLC22A4, RUNX1, and SUMO4 polymorphisms are not associated with rheumatoid arthritis: a ca 2006 Jul OBJECTIVE: To replicate the association reported in Japanese individuals of functional SLC22A4 and RUNX1 polymorphisms with rheumatoid arthritis (RA), and to test the possible role in this trait of a functional variant of the SUMO4 gene that was shown to be associated with another related autoimmune disease, type 1 diabetes (T1D). METHODS: Our study population consisted of 886 patients with RA and 987 healthy controls. All subjects were of Spanish Caucasian origin. We conducted a case-control association study with 6 single-nucleotide polymorphisms (SNP) spanning the SLC22A4 gene. SNP mapping in the RUNX1 gene associated with RA in a Japanese population and a SUMO4 polymorphism associated with T1D were also studied. RESULTS: No statistically significant differences between patients with RA and healthy controls were observed when comparing the distribution of the genotypes or alleles of any of the SLC22A4 polymorphisms tested. Similarly, no evidence of association between RA and the SLC22A4 haplotype previously reported to be associated in a Japanese population was found. With regard to the RUNX1 and SUMO4 SNP, we did not observe statistically significant differences in the distribution of genotypes or alleles between patients with RA and healthy controls. CONCLUSION: These results suggest that the SLC22A4, RUNX1, and SUMO4 polymorphisms analyzed do not confer a relevant role in susceptibility to RA in the Spanish population.
17975311 Asymptomatic pericardial effusion in patients with rheumatoid arthritis. 2008 OBJECTIVES: The aim of this study was to determine the frequency and clinical correlates of asymptomatic pericardial effusion (PE) detected by echocardiography in patients with rheumatoid arthritis (RA). METHODS: Echocardiography and electrocardiography were performed in 87 consecutive patients with RA. Asymptomatic PE was correlated with electrocardiographic changes and laboratory findings. RESULTS: Among 87 patients with RA, 20 patients (23%) had PE and 28 patients (32%) had hypoalbuminemia. The patients with PE had significantly lower serum albumin level (p < 0.001), higher rheumatoid factor (RF)titer (p = 0.002) and higher incidence of impaired left ventricular relaxation (55 vs. 28%, p = 0.028) and tended to have a higher incidence of PR-segment depression than those without PE (p = 0.085). When five variables (PR-segment depression, C-reactive protein, serum albumin, RF and impaired left ventricular relaxation) were used in the multivariate analysis, serum albumin (p = 0.003, Odds ratio = 0.131) and RF (p = 0.020, Odds ratio = 3.775) emerged as significant variables related to the presence of asymptomatic PE. CONCLUSIONS: In addition to pericardial inflammation due to more severe RA, hypoalbuminemia was an important factor associated with the presence of asymptomatic PE.
17552048 Changes in biomarkers of inflammation and bone turnover and associations with clinical eff 2007 Jul OBJECTIVE: To determine if changes in biomarkers of inflammation and bone turnover in response to treatment with infliximab plus methotrexate (MTX) versus MTX alone are associated with improvement in clinical measures of signs, symptoms, and structural damage in early rheumatoid arthritis. METHODS: Sera were collected from patients in the ASPIRE study who received 3 mg/kg (n = 48) or 6 mg/kg infliximab plus MTX (n = 55), or MTX alone (n = 41). Several baseline biomarker levels correlated with changes in median percentage of American College of Rheumatology improvement (ACR-N), 50% improvement in ACR response (ACR50), and van der Heijde-modified Sharp score (vdHSS) at Week 54. RESULTS: Infliximab plus MTX treatment resulted in more rapid decreases in levels of matrix metalloproteinase-3 (MMP-3), intercellular cell adhesion molecule-1, interleukin 8 (IL-8), and tumor necrosis factor-a than treatment with MTX alone. Baseline levels and decreases from baseline to Weeks 6 and 54 in MMP-3 correlated with improvement in ACR-N response at Week 54. An increase in IL-8 levels from baseline to Week 54 correlated with worsening in vdHSS at Week 54 in the MTX-alone group. Regression analysis of markers at baseline showed that MMP-3 was the only variable associated with ACR50 response and less worsening in vdHSS at Week 54. CONCLUSION: Treatment with infliximab plus MTX resulted in a rapid decrease in inflammation markers. MMP-3 levels at different timepoints were consistently associated with clinical improvements at Week 54 in the infliximab plus MTX group, while increases in IL-8 levels correlated with a worsening in vdHSS at Week 54 in the MTX-alone group.