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ID PMID Title PublicationDate abstract
22903258 Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differ 2013 Jul OBJECTIVES: MicroRNAs, a class of noncoding RNAs, play roles in human diseases. MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis. The purpose of this study was to analyze the expression pattern of miR-223 in rheumatoid arthritis (RA) synovium and examine the suppression of osteoclastogenesis from human peripheral blood mononuclear cells (PBMC) by overexpression of miR-223. METHODS: Expression of miR-223 in synovium from RA patients was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and section in situ hybridization. MiR-223 was overexpressed in an osteoclastogenesis coculture system with PBMC and RA synovial fibroblast. At 3 weeks after transfection of double-stranded miR-223, the formation of tartrate-resistant acid phosphatase (TRAP)-stained multinucleated cells was analyzed to evaluate the inhibitory effect of miR-223 on osteoclastogenesis. RESULTS: MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium. MiR-223 was expressed in the superficial and sublining layers, and macrophages, monocytes, and CD4 T cells also expressed miR-223. The number of TRAP-positive multinucleated cells was significantly decreased by overexpression of miR-223 in a dose-dependent manner. The expression of osteoclastogenesis marker genes was significantly down-regulated by miR-223 overexpression. CONCLUSION: MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro. This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients.
24341236 [Cell and cytokine markers in the synovial membrane in rheumatoid arthritis]. 2013 Sep The paper considers the morphological signs of rheumatoid synovitis, their association with clinical manifestations and therapy. Synovial changes in rheumatoid arthritis indicate that there is variability and subclasses of this disease. There is evidence that it is necessary to quantify morphological changes, by using digital imaging techniques, and to study the classes and subclasses of cellular elements of inflammation. Inflammatory infiltration of the synovial membrane contains T and B lymphocytes and their subclasses. The expression of cell markers and proinflammatory and anti-inflammatory cytokines is characterized. The points of therapy with genetically engineered biological agents are shown. Further morphological investigation of the synovial membrane should aim to detect the diagnostic and prognostic signs of synovitis and to identify risk-group patients with the persistent and destructive types of the disease. The findings may be of importance in studying the pathogenesis, identifying the subclasses of rheumatoid arthritis, and searching for new effective applications of the biological agents.
25715572 [The effect of selected physical procedures on mobility in women with rheumatoid arthritis 2014 Dec Electrotherapy, including iontophoresis and magnetic field, is one of the most commonly used physical procedures in the treatment of rheumatoid arthritis (RS). THE AIM OF THE PAPER: To evaluate the effect of iontophoresis and magnetic field procedures on the intensity and frequency of pain sensation, administration of analgesics, limitation of knee joint mobility and comparative evaluation of analgesic effect s of the applied procedures. MATERIAL AND METHODS: The study included a group of 60 female patients affected by RS with knee joint pain. Patients were randomly assigned to 3 equally-numbered groups. Group I was subjected to 20 iontophoresis procedures. Group II underwent 20 procedures with magnetic field. Group III was treated with 20 procedures combining both iontophoresis and magnetic field. Each iontophoresis procedure lasted 20 minutes, whereas the magnetic field procedure took 30 minutes. All study participants were evaluated in relation to pain sensation after and before the treatment with VAS (Visual Analogue Scale) and Latinen scale. RESULTS: After a 4-week therapy in all the three groups there was a statistically significant decrease in pain perception with VAS scale and with all domains of Laitinen scale excluding the limitation of physical activity criterion. The comparative evaluation of statistically important differences after the therapy between the groups revealed marked decrease of pain perception in groups I and II comparing to group II. There were no significant differences between groups I and III. CONCLUSIONS: Iontophoresis and magnetic field treatments demonstrate effective analgesic property in female patients with rheumatoid arthritis. The conducted studies showed the highest analgesic effects for both treatments used.
24561411 Assessment of fatigue in rheumatoid arthritis (by Functional Assessment of Chronic Illness 2014 Mar BACKGROUND: Patients with rheumatoid arthritis (RA) mention fatigue as one of their most annoying problems. Measuring fatigue, understanding its contributory factors, and treating it as a feasible target lead to better patient outcome and improved quality of life. The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System is a collection of health-related quality-of-life questionnaires targeted to the management of chronic illness. OBJECTIVE: The objective of this study was to evaluate fatigue using FACIT-Fatigue (FACIT-F) score and its relation to disease activity (using Disease Activity Score [DAS28] and Clinical Disease Activity Index [CDAI] score) and anemia in RA patients. METHODS: A total of 100 RA patients were evaluated for fatigue using FACIT-F score, for disease activity using DAS28 and CDAI scores, for anemia using hemoglobin levels. Correlation studies were done using Pearson test. RESULTS: Functional Assessment of Chronic Illness Therapy-Fatigue showed positive association with DAS28 (P < 0.001; r = -0.80) and CDAI (P < 0.001; r = -0.83). Considering various components of DAS28 and CDAI, FACIT-F showed significant correlation with tender joint count (P < 0.001; r = -0.73), swollen joint count (P < 0.001; r = -0.76), patient global assessment (P < 0.001; r = -0.72), and evaluator global assessment (P < 0.001; r = -0.75). Erythrocyte sedimentation rate had no association with the fatigue (P = 0.217). No association was observed between fatigue and hemoglobin levels (P = 0.203). CONCLUSION: The fatigue experienced by the patients with RA is strongly associated with the severity of disease activity and is independent of anemia.
24354438 Early rheumatoid arthritis 6 years after diagnosis is still associated with high direct co 2014 OBJECTIVES: To calculate total costs over 6 years after diagnosis of early rheumatoid arthritis (RA). METHOD: In the longitudinal prospective multicentre TIRA study, 239 patients from seven units, diagnosed in 1996-98, reported regularly on health-care utilization and the number of days lost from work. Costs were obtained from official databases and calculated using unit costs (Swedish kronor, SEK) from 2001. Indirect costs were calculated using the human capital approach (HCA). Costs were inflation adjusted to Euro June 2012, using the Swedish Consumer Price Index and the exchange rate of June 2012. Statistical analyses were based on linear mixed models (LMMs) for changes over time. RESULTS: The mean total cost per patient was EUR 14,768 in year 1, increasing to EUR 18,438 in year 6. Outpatient visits and hospitalization decreased but costs for surgery increased from EUR 92/patient in year 1 to EUR 444/patient in year 6. Drug costs increased from EUR 429/patient to EUR 2214/patient, mainly because of the introduction of biologics. In year 1, drugs made up for 10% of direct costs, and increased to 49% in year 6. Sick leave decreased during the first years but disability pensions increased, resulting in unchanged indirect costs. Over the following years, disability pensions increased further and indirect costs increased from EUR 10,284 in year 1 to EUR 13,874 in year 6. LMM analyses showed that indirect costs were unchanged whereas direct costs, after an initial fall, increased over the following years, leading to increasing total costs. CONCLUSIONS: In the 6 years after diagnosis of early RA, drug costs were partially offset by decreasing outpatient visits but indirect costs remained unchanged and total costs increased.
23219774 Different effects of biological drugs in rheumatoid arthritis. 2013 Mar Biological drugs have brought new hope to patients with rheumatoid arthritis (RA) in whom previously existing treatments could not control inflammation, joint destruction, or the progression of disability. The five currently available TNF blockers are approved for treating RA patients, but they have different structures, morphology, pharmacokinetic properties, and activity. Randomised clinical trials (RCTs) have shown that they improve the signs and symptoms of both early and long-standing RA and other inflammatory arthritides, prevent radiographic progression, and improve the patients' health-related quality of life. However, they are more effective in combination with methotrexate (MTX) than alone. Combined treatment is generally well tolerated, and seems to be relatively safe in the short term, as confirmed by RCTs, long-term observational studies and in clinical practice. Patients who fail to respond or develop adverse effects - when treated with one anti-TNF agent can be successfully treated with a second TNF antagonist. However, in the case of primary failure, it is possible that biological agents with a different mechanism of action may be more successful. Tocilizumab alone or in combination with MTX is more effective than MTX monotherapy in reducing disease activity over 24 weeks. Abatacept is well tolerated and retains its efficacy over time, as does rituximab in non-responders to other anti-TNF drugs. Finally, although these drugs improve the quality of life of RA patients, they considerably increase direct medical costs.
23836776 Association of tobacco exposure and reduction of radiographic progression in early rheumat 2013 Dec OBJECTIVE: To investigate the initial response to treatment and risk of radiographic disease progression in current smokers (S), ex-smokers (EX), and nonsmokers (NS) in a prospective early arthritis cohort and to analyze the influence of smoking cessation on arthritis outcome. METHODS: The ESPOIR cohort is a prospective cohort study monitoring clinical, biologic, and radiographic data for patients with inflammatory arthritis lasting 6 weeks to 6 months. We examined the influence of smoking status on disease presentation (baseline characteristics) and therapeutic response at 1 year. Risk of structural progression at 12 months, defined as change in the modified Sharp/van der Heijde score ≥1, was analyzed by multivariate regression adjusted for potential confounders (age, sex, joint erosion at inclusion, educational level, positivity for rheumatoid factor or anti-cyclic citrullinated peptide 2 antibodies, and shared HLA-DRB1 epitope). RESULTS: A total of 813 patients were included; 641 (79%) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for rheumatoid arthritis (RA). At inclusion, 138 (21.5%) were S patients, 168 (26.2%) were EX patients, and 335 (52.3%) were NS patients. Baseline acute-phase indicator values were significantly lower for S patients than EX and NS patients (mean ± SD erythrocyte sedimentation rate was 24.2 ± 18.2 mm/hour versus 33.4 ± 28.0 and 31.4 ± 25.0 [P = 0.02], respectively, and mean ± SD C-reactive protein level was 17.7 ± 28.0 mg/dl versus 28.5 ± 42.5 and 21.4 ± 29.0 [P = 0.01], respectively). Smoking status had no influence on Disease Activity Score in 28 joints, Health Assessment Questionnaire score, EULAR response, or use of disease-modifying antirheumatic drugs and biologic therapy in the first 12 months of followup (P > 0.05). The adjusted risk for structural disease progression was associated with active smokers (odds ratio 0.50 [95% confidence interval 0.27-0.93], P = 0.028). Sixteen patients had stopped smoking at 12 months, with no significant difference in observed outcomes from other patients. CONCLUSION: In this large prospective cohort of patients with early arthritis, smoking status had no significant effect on disease activity and disability but did reduce 1-year radiographic disease progression. The antiinflammatory role of nicotine may explain the lower systemic inflammation and structural disease progression in current smokers with early RA.
25366205 Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid int 2014 Sep BACKGROUND & OBJECTIVES: Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker. METHODS: Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied. RESULTS: Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; p0 = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), p0 =0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (≥ 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75 th percentile value among normal controls (≥ 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; p0 <0.001) and (62.5 vs 25%; P<0.001) respectively]. INTERPRETATION & CONCLUSIONS: Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA.
23179004 Same-day or historical ESR for disease activity score measurement: does it matter? 2013 Feb Several guidelines recommended routine use of Disease Activity Score-28 (DAS28) to monitor disease and the response to treatment for rheumatoid arthritis (RA). In practice, it may be appropriate to use historical erythrocyte sedimentation rate (ESR) values in place of same-day ESR, thereby preventing unnecessary delay in adjusting intervention. We asked whether ESR blood samples taken up to 3 months prior to the clinic appointment were adequate to accurately assess RA disease activity using the DAS28. RA patients (N = 66) who met the inclusion criteria were assessed at baseline and ESR obtained on the day of review to calculate the DAS28 and compared with the DAS28 derived from the latest previous ESR (mean interval, 38.6 days; range, 6-99 days). Limits of agreement (LoA) were used to assess the agreement between the DAS28 pairs. The mean age of the participants was 61.5 years (range, 20-83 years), with mean disease duration of 11.0 years (range, 0.1-40 years). Comparing the DAS28 using same-day ESR versus pre-recorded historical ESR showed a small statistical difference (mean, -0.09; 95 %CI, -0.1602 to -0.017) in the DAS28 score. The calculated LoA (-0.66 and 0.48) demonstrated acceptable agreement between DAS28 pairs, with 7.6 % of patients residing outside the LoA, all of whom had a significant treatment change. Disease misclassification occurred in 9.1 % of patients who were close to disease activity boundaries. Our results indicate that differences in the DAS28 due to a previous or same-day ESR are unlikely to be clinically significant for RA patients with established disease. A decision to adjust treatment therefore may be confidently made for most patients using the most recent ESR for calculating the DAS28, provided there was no major change in treatment since the last ESR measurement.
24469604 Comparative effectiveness of cycling of tumor necrosis factor-α (TNF-α) inhibitors versu 2014 May Alternative tumor necrosis factor-α (TNF-α) inhibitors and non-TNF biologics are available as treatment options for rheumatoid arthritis patients who exhibit inadequate response to TNF-α inhibitor (TNF-IR patients). These agents have considerable efficacy compared with placebo, but head-to-head comparisons among these agents have not been performed. The objective of this study was to use Bayesian approach to compare the effectiveness of cycling TNF-α inhibitors versus switching to non-TNF biologics in TNF-IR patients. A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 and the health assessment questionnaire (HAQ) score change at six months. Bayesian outcomes were calculated as the probability that OR is greater than one and HAQ score change difference is less than zero. Compared with TNF-α inhibitors, non-TNF biologics were associated with higher ACR response rates; in ACR20, the OR was 1.639 for abatacept [P(OR > 1) = 90.7 %], 1.871 for rituximab [P(OR > 1) = 96.2 %] and 3.52 for tocilizumab [P(OR > 1) = 99.9 %]. Similar trends were shown in the HAQ change comparison; the median differences (MD) were -0.259 for abatacept [P(MD < 0) = 100 %], -0.160 for rituximab [P(MD < 0) = 98.2 %], and -0.200 for tocilizumab [P(MD < 0) = 99.3 %]. In conclusion, switching to non-TNF biologics was more effective than cycling TNF-α inhibitor in TNF-IR patients.
22915619 Rituximab dissociates the tight link between disease activity and joint damage in rheumato 2013 Jan BACKGROUND/OBJECTIVE: Progression of joint damage is linked to disease activity. This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate (MTX). It is hitherto unknown if this may also be true for therapies targeting B-cells. We thus evaluated if rituximab (RTX) therapy inhibits joint damage irrespective of its effects on disease activity. METHODS: We used a random 90% sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis (RA) receiving MTX (n=188) or MTX+RTX 1000 mg (n=204). Patients were divided into low, moderate and high disease activity at one year of treatment by simplified disease activity index (low disease activity (LDA), moderate disease activity (MDA), high disease activity (HDA)), or by swollen joint count (SJC) or C reactive protein (CRP) tertiles. Progression of damage by the Genant modified total Sharp score (TGSS) was compared between therapies (Kruskal-Wallis, Wilcoxon tests) for each of these subgroups. RESULTS: In patients treated with MTX, 1-year progression of TGSS In LDA, MDA and HDA was 0.40±0.88, 1.04±1.73, and 1.31±3.02, respectively. In contrast, on RTX+MTX, TGSS progression was 0.38±1.07, 0.39±1.28, and -0.05±0.44, respectively (for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group: p=0.003 and p=0.05, respectively). Additional analyses (tertiles of SJC, CRP, and matching for disease activity) confirmed the primary analysis. CONCLUSIONS: In early RA, progression of joint damage increases with increasing disease activity on MTX. RTX plus MTX retards damage independently of its effects on disease activity, since even in HDA destruction is halted, contrasting MTX monotherapy. This indicates that beyond cytokine blockade (TNF- and IL-6 inhibitors), also cell-directed therapy (anti-CD20 antibody) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage.
23967327 Hypoxia-inducible factor-1α and interleukin 33 form a regulatory circuit to perpetuate th 2013 Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines, and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA). Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating the disease severity of RA. Hypoxia-inducible factor-1α (HIF-1α) showed increased expression in RA synovium and could regulate a number of inflammatory cytokine productions. Nevertheless, its correlation with IL-33 remains largely unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA patient synovial fluids, with upregulated expression of HIF-1α and IL-33 in the synovial fibroblasts. Knocking down HIF-1α compromised IL-33 expression in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1α expression in RASF substantially upregulated IL-33 levels. HIF-1α promoted the activation of the signalling pathways controlling IL-33 production, particularly the p38 and ERK pathways. Moreover, we showed for the first time that IL-33 in turn could induce more HIF-1α expression in RASF, thus forming a HIF-1α/IL-33 regulatory circuit that would perpetuate the inflammatory process in RA. Targeting this pathological pathway and HIF-1α may provide new therapeutic strategies for overcoming the persistent and chronic inflammatory disease.
23731644 Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: systematic revi 2014 Jan OBJECTIVE: To systematically analyze literature with the aim of examining whether rheumatoid factor (RF) is a predictor of response to tumor necrosis factor (TNF) antagonists in rheumatoid arthritis (RA). METHODS: A systematic review and meta-analysis of observational studies were conducted. All studies on the association of baseline RF (titer and/or status) and response to any TNF antagonists, or with enough information to estimate this association were included. Qualitative analysis and meta-analysis using random-effects approach by type of outcome response and RF test was performed. Risk of publication bias was also evaluated. RESULTS: The systematic review included 18 studies of 4163 identified articles, involving 5703 patients with homogeneous baseline characteristics. The most common outcome to assess response was European League Against Rheumatism (EULAR) response criteria, normally merging good and moderate categories as response. The weighted mean difference (WMD) of baseline IgM RF titer in meta-analysis was higher in the non-responders group [-101.58 (95% CI -156.58,-46.59) I2=0.0]. Combined odds ratios (ORs) of positive IgM RF, positive IgA RF, and positive IgG RF to achieve good/moderate response were 1.08 (0.80, 1.47), I2=40.9%; 0.83 (0.39, 1.73), I2=39.8%, and 1.30 (0.48, 3.51), I2=62.9%, respectively. We did not find an association between a positive IgM RF and EULAR good response or remission. CONCLUSIONS: This meta-analysis does not support baseline IgM RF titer as a predictor of response to TNF antagonists in RA. However, this conclusion is hampered by high heterogeneity in the studies included in this meta-analysis.
23185038 Myocardial ischaemia without obstructive coronary artery disease in rheumatoid arthritis: 2013 Jan OBJECTIVE: RA is associated with increased cardiovascular events, reportedly to equal diabetes mellitus (DM). The presence of myocardial ischaemia was assessed in asymptomatic high-risk RA patients and compared with patients with DM and a healthy control group. METHODS: Eighteen consecutive non-diabetic RA patients without known cardiovascular disease who developed a new carotid atheromatic plaque during the last 3 years were matched 1:1 for traditional cardiovascular risk factors with asymptomatic type 2 DM patients and 1:2 with asymptomatic non-RA, non-DM control subjects. After dobutamine stress contrast echocardiography with wall-motion and perfusion evaluation, coronary angiography was performed in those with positive stress tests. RESULTS: Ischaemia by echocardiography was found in 67% of RA patients; this was significantly higher than controls (31%, P = 0.019) but comparable to those with DM (78%, P = 0.71). Angiography performed in eight consenting RA patients was normal in four, revealed non-flow-limiting coronary atheromatic lesions in two and significant lesions in two patients. RA patients with ischaemia had CRP serum levels significantly higher by six-fold compared with those with normal stress echocardiography. CONCLUSION: Asymptomatic RA patients may display myocardial ischaemia at similar levels to DM patients but with low prevalence of obstructive coronary artery disease. Microvascular abnormalities associated with increased inflammatory response may account for these findings. Their exact nature and significance require further evaluation.
24706006 Current smoking status is a strong predictor of radiographic progression in early rheumato 2015 Aug OBJECTIVES: To study clinical predictors for radiographic progression after 1 year in an early rheumatoid arthritis (RA) trial. METHODS: In the SWEFOT trial population, disease modifying antirheumatic drug (DMARD) naïve RA patients started methotrexate; 3-month responders (DAS28 <3.2) continued (n=147), while non-responders were randomised to addition of sulfasalazine+hydroxychloroquine (n=130) or infliximab (n=128). X-rays were scored by the Sharp-van der Hejde score (SHS) method and radiographic progression was defined as a ≥5 increase after 1 year. Potential baseline predictors of radiographic progression were tested using multivariable logistic regression, adjusted for potential confounders. RESULTS: 79 of 311 patients with available radiographs at baseline and follow-up had radiographic progression. The following baseline parameters were independent predictors of radiographic progression at 1 year: baseline erosions (adjusted OR=2.29, 95% CI 1.24 to 4.24), erythrocyte sedimentation rate (adjusted OR per tertile increase=1.72, 95% CI 1.12 to 2.65) and C-reactive protein (adjusted OR per tertile increase=1.52, 95% CI 1.03 to 2.26). Current smoking was an independent predictor of radiographic progression (adjusted OR=2.17, 95% CI 1.06 to 4.45). These results remained after further adjustment for treatment strategy. Three-dimensional matrix including current smoking status, erosions and C-reactive protein tertiles showed a 12-63% risk gradient from patients carrying none compared with all predictors. Rheumatoid factor (RF)/anti-cyclic citrullinated peptide (anti-CCP) positivity did not significantly predict radiographic progression using SHS increase ≥5 as cut-off. In a secondary exploratory analysis using cut-off >1, both RF and anti-CCP positivity were significant predictors in the unadjusted, but not the adjusted analyses. The other parameters also remained significant using this lower cut-off. CONCLUSIONS: In addition to previously described predictors, we identified smoking as a strong independent risk factor for radiographic progression in early RA. TRIAL REGISTRATION NUMBER: NCT00764725.
24441150 Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab t 2014 May OBJECTIVE: The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity. METHODS: Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission. RESULTS: Of 333 patients assessed, 278 (137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks (mean ΔmTSS at week 52 = 2.56 vs 3.30, P < 0.001). CONCLUSION: Delayed addition of adalimumab in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab. However, the accrual of significant structural damage during blinded placebo + MTX therapy contributed to the persistence of differences between the treatment strategies, suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab + MTX combination therapy. Trial registration. ClinicalTrials.gov (http://clinicaltrials.gov/), NCT00870467.
23773642 Association of STAT4 gene polymorphism with increased susceptibility of rheumatoid arthrit 2013 Apr OBJECTIVE: Several studies have reported STAT4 polymorphism is strongly associated with increased susceptibility to rheumatoid arthritis (RA). However, a study from China showed no association between STAT4 and RA susceptibility in a Chinese Han subpopulation. Since the northern Hans are known to be genetically different from the southern Hans, the aim of this study was to investigate the association of STAT4 polymorphism with RA in a large cohort of a northern Chinese Han subpopulation. METHODS: 640 RA patients and 662 healthy controls were enrolled. DNA samples were genotyped for STAT4 rs7574865 by direct sequencing. The association of single nucleotide polymorphism (SNP) rs7574865 with RA susceptibility was calculated and the relationship between rs7574865 polymorphism and RA subgroups stratified by clinical features was estimated. RESULTS: We confirmed a significant association of STAT4 rs7574865 polymorphism with RA susceptibility in northern Chinese Han population. The frequency of the minor T allele in RA was significantly higher than in healthy controls (35.2% vs. 31.1%; P = 0.029, OR 1.2 [95% CI 1.02-1.41]). There was also a significant difference in the distribution of the genotypes of SNP rs7574865 between RA patients and healthy controls (P = 0.02). Stratification analyses showed no associations between the genetic risk and clinical/serologic features, but a potential high frequency of TT genotype in a rheumatoid factor-negative subgroup, although it did not reach statistical significance (P = 0.084, OR 2.01 [95% CI 0.91-4.45]). CONCLUSION: STAT4 rs7574865 is significantly associated with RA susceptibility in northern Chinese Han subpopulations. The genetic differences of Han subpopulations should be considered when genetic susceptibility for diseases is studied.
24050519 A detailed analysis of treatment delay from the onset of symptoms in early rheumatoid arth 2014 OBJECTIVES: A treatment delay of more than 12 weeks can negatively affect treatment response in rheumatoid arthritis (RA). Our aim was to quantify the different stages of delay before RA treatment in different rheumatology centres and to explore influencing factors. METHOD: A total of 156 disease-modifying anti-rheumatic drug (DMARD)-naive early RA patients were included from eight practices: one academic hospital, five general hospitals, and two private practices. Eight different types of delay were defined from symptom onset until treatment initiation. Information on the duration of each stage of delay was collected from the patient, their general practitioner (GP), and patient files at the rheumatology practice. Patient/GP demographics and disease activity/severity parameters were recorded. RESULTS: The median total delay from symptom onset until treatment initiation was 23 weeks whereas patient-, GP- and rheumatologist-related median delay was 10, 4, and 7 weeks, respectively. Only 21.6% of the patients had a total delay of less than 12 weeks. The total median delay in private rheumatology practices was less than in academic and general hospitals (p < 0.001). Furthermore, RA patients treated within 12 weeks of symptom onset showed a higher level of disease activity. The duration of rheumatologist-related delay was inversely correlated with disease activity parameters. Patients with morning stiffness were treated, on average, 3 weeks sooner than those without morning stiffness (p < 0.006). CONCLUSIONS: In only one out of five early RA patients was treatment initiated within 12 weeks of symptom onset, as recommended. Patient-related delay contributed most to overall delay. Disease activity and type of rheumatology centre are pivotal determinants of delay.
25472711 Oro-facial evaluation of women with rheumatoid arthritis. 2015 May Rheumatoid arthritis (RA) is an aggressive articular autoimmune disease that causes deformities and disability. The temporomandibular joint (TMJ) might be affected by this disease. Few controlled studies have evaluated bite force (BF) and oro-facial manifestations of this disease. To characterise oro-facial alterations in patients with RA, correlate these results with clinical and disease activity parameters and correlate BF with hand strength (HS). A cross-sectional study of 150 women was performed, (75 RA patients (RA group) and 75 healthy individuals (control group). The presence of articular sounds, pain on palpation of masseter, temporal and TMJ lateral pole, changes in occlusion, range of mandibular motion, measurement of BF in the incisor and molar regions and assessment of HS were evaluated. In relation to oro-facial evaluation there were statistical differences between the groups. There was correlation between BF and HS, in the RA group, this correlation was consistent in patients with natural teeth. Patients with RA had lower scores (P < 0·05) in the HAQ, DASH and OHIP-14 questionnaires than the control group. Inverse correlations were found between BF and HAQ, but not between BF and DAS-28, DASH and OHIP-14 questionnaires in the RA group. The women with RA presented more signs and symptoms in the oro-facial region and had a lower BF than the women in the control group. BF was inversely correlated with the overall function (evaluated by the HAQ) in the patients with RA, and there were correlations between BF and HS in the RA patients and in the control group.
23772080 Associations of alcohol use with radiographic disease progression in African Americans wit 2013 Sep OBJECTIVE: To investigate the associations of alcohol consumption and radiographic disease progression in African Americans with recently diagnosed rheumatoid arthritis (RA). METHODS: Patients with RA included in the study were participants in the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry. Patients were categorized based on self-reported alcohol consumption; those consuming < 15 beverages per month versus those with ≥ 15 per month. Association of radiographic disease progression over a 1-year to 3-year period of observation with alcohol consumption was evaluated using multivariate generalized estimating equations. RESULTS: Of 166 patients included in the study, 39% reported that they had never consumed alcohol. Of the 61% who had consumed alcohol, 73% reported that they consumed on average < 15 alcoholic beverages per month and 27% reported consuming ≥ 15 per month. In multivariate analysis, consumption of ≥ 15 alcoholic beverages per month was associated with an increased risk of radiographic disease progression (p = 0.017). There was no evidence of a relationship in those consuming < 15 beverages per month (p = 0.802). CONCLUSION: There appears to be a dose-dependent relationship between alcohol use and radiographic disease progression in RA. Individuals who consume 15 or more alcoholic beverages per month may have faster rates of radiographic joint damage than those with lower levels of consumption.