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ID PMID Title PublicationDate abstract
22409880 Ultrasonographic measures of synovitis in an early phase clinical trial: a double-blind, r 2012 Mar OBJECTIVES: To test the sensitivity to change of ultrasonographic endpoints in early phase clinical trials in subjects with active rheumatoid arthritis (RA). METHODS: A double-blind, placebo and comparator controlled, randomised, two-centre study investigated the effect on synovial thickness and vascularity of 28 days repeat daily oral dosing of 60 mg of the inducible nitric oxide synthase inhibitor GW274150 or 7.5 mg prednisolone in RA. Fifty patients with DAS28 scores ≥4.0 were assigned to 3 treatment arms of 17, 19 and 14 (on placebo, GW274150 and prednisolone respectively). Synovial thickness and vascularity of all 10 metacarpophalangeal joints were assessed by ultrasonography using a semi-quantitative scale at baseline (Day 1), Day 15 and Day 28. Vascularity was also measured quantitatively by power Doppler area. RESULTS: At Day 28, the GW274150 group showed a trend towards reduction in synovial thickness compared with placebo, with an adjusted mean decrease of 33% (p=0.072); the prednisolone group decreased significantly by 44% (p=0.011). Similarly, there was a trend to reduced synovial vascularity with GW274150 by 42% compared with placebo (p=0.075); prednisolone resulted in a statistically significant decrease of 55% (p=0.012). There was a 55% decrease in power Doppler area for GW274150, compared with placebo although the result was not statistically significant (p=0.375). Prednisolone 7.5 mg resulted in a highly statistically significant decrease of 95% (p=0.003). CONCLUSIONS: This study advocates the use of ultrasonographic measures of metacarpophalangeal joint synovitis as an endpoint for clinical studies assessing therapeutic potential of new compounds in small patient cohorts over 28 days.
22118371 The effect of smoking on response and drug survival in rheumatoid arthritis patients treat 2012 Feb OBJECTIVES: Smoking has been associated with higher disease activity and poor response to anti-tumour necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). We wanted to study the effect of smoking on response to therapy, disease activity measures, and drug survival in RA patients starting their first anti-TNF drug. METHODS: In 2005, RA patients in a voluntary rheumatology biologics register in Southern Sweden answered a questionnaire that included smoking habits. The primary endpoint comprised the European League Against Rheumatism (EULAR) response criteria at 3, 6, and 12 months. Secondary endpoints were the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) response criteria, and drug survival. RESULTS: Between 1999 and 2005, 23% of RA patients (216/934) in Southern Sweden were current smokers at the start of anti-TNF therapy. Smoking did not influence disease activity at baseline. Heavy smokers had the poorest drug survival. Current smoking was a negative predictive factor for EULAR response at the 3-month follow-up [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.87, p = 0.012], and for SDAI response at 3 months (OR 0.45, 95% CI 0.27-0.77, p = 0.003) and 6 months (OR 0.47, 95% CI 0.25-0.88, p = 0.02). A pack-year history of 11-20 was a negative predictive factor for SDAI response at 12 months (OR 0.30, 95% CI 0.13-0.70, p = 0.005). Smokers had higher visual analogue scale (VAS) global scores, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) at 3 months. CONCLUSION: Current smoking was predictive of poor response to anti-TNF treatment for up to 12 months and heavy smokers had the poorest drug survival.
21345290 Effects of naproxen and sulphasalazine or methotrexate on hypothalamic-pituitary-adrenal a 2011 Jan OBJECTIVES: To study the effects of antirheumatic drugs on hypothalamic-pituitary-adrenal (HPA) axis activity in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with recent-onset active RA were studied before antirheumatic treatment, after 2 weeks of naproxen, and after 5½ months of additional treatment with sulphasalazine or methotrexate. The results before treatment were compared with those obtained in 20 age and sex-matched healthy controls (HC). Activity of the HPA-axis was assessed under basal conditions and during insulin tolerance tests (ITT). The ex-vivo production of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α) and IL-6 in whole blood samples was measured with and without stimulation by LPS. RESULTS: At baseline, plasma ACTH and cortisol levels were not different between patients with RA and HC. The unstimulated production of IL-6 was significantly higher in RA patients than in HC. After 2 weeks of treatment with naproxen, urinary cortisol excretion decreased significantly (p=0.03), and the area under the curve for plasma cortisol during the ITT was significantly lower (p=0.015). The LPS stimulated production of IL-1β was significantly lower compared with baseline. After 6 months, basal plasma, salivary and urinary cortisol levels, and plasma cortisol and ACTH levels during the ITT, were all unchanged in comparison to the pre-treatment period. The unstimulated ex-vivo production of IL-1β was significantly lower than before treatment. CONCLUSIONS: Our results suggest that the non-steroidal anti-inflammatory drug naproxen suppresses the HPA-axis in the first weeks of treatment. After 6 months, this suppressive effect is no longer present, suggesting the existence of adaptive mechanisms.
21267572 Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in 2012 May Rheumatoid arthritis (RA) is an autoinflammatory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like features, and RA patients have genomic instability and relaxation of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inflammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms were investigated by PCR-RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ(2)-tests. RA patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65-16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19-3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67-5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a significant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA.
22782007 Regenerative medicine in rheumatic disease-progress in tissue engineering. 2012 Aug Joint destruction occurs in both osteoarthritis and rheumatoid arthritis. Even in the era of biologic agents, this destruction can be delayed but not averted. As cartilage has limited ability to self-regenerate, joint arthroplasty is required. Here, we outline current tissue engineering procedures (including autologous chondrocyte implantation and in situ mesenchymal stem cell recruitment) that are routinely applied for the regenerative treatment of injured or early osteoarthritic cartilage. Potential future regenerative therapies, including administration of multipotent or pluripotent stem cells, are also discussed. In the future, cell-free, material-based (for cartilage lesions) or cell-free, factor-based (for osteoarthritic cartilage) therapies to facilitate the recruitment of repair cells and improve cartilage metabolism are likely to become more important. Moreover, delivery of anti-inflammatory factors or immunomodulatory cells could be a regenerative treatment option for rheumatoid arthritis. Tissue engineering faces a crucial phase to translate products into clinical routine and the regulatory framework for cell-based products in particular is an important issue.
21822659 Impact of patient and disease characteristics on therapeutic success during adalimumab tre 2012 Sep The objective of this study was to use data from a noninterventional study to evaluate the effectiveness of adalimumab in rheumatoid arthritis (RA) patients during routine clinical practice and to explore the potential impact of patient and disease characteristics in response to adalimumab therapy. A total of 2,625 RA patients with specified data at baseline (prior to initiating adalimumab treatment) and 12 months entered this study between April 2003 and March 2009. We evaluated response to adalimumab therapy and conducted stepwise regression and subgroup analyses of factors influencing therapeutic response. During the 1-year adalimumab treatment period, disease activity decreased from a baseline mean disease activity score-28 joints (DAS28) of 5.9-3.9, while functional capacity improved from 59.0 to 68.4 Funktionsfragebogen Hannover (FFbH) percentage points. In multivariate regression models, high baseline DAS28 was the strongest positive predictor for decrease in disease activity, and high baseline functional capacity was associated with reduced gains in functional capacity. Male gender was a positive predictor of therapeutic response for both disease activity and functional capacity, while older age and multiple previous biologics were associated with a reduced therapeutic response. Subset analyses provided further support for the impact of baseline DAS28, FFbH, and prior biologic therapy on therapeutic response during treatment. We conclude that treatment with adalimumab leads to decreased disease activity and improved function during routine clinical practice. Patients with high disease activity and low functional capacity are particularly benefitted by adalimumab therapy.
22173958 The effectiveness of Echinacea extract or composite glucosamine, chondroitin and methyl su 2013 Mar The study aimed to investigate the effect of the oral administration for 15 days of either Echinacea (E) or genuphil (a composite of chondroitin sulphate, glucosamine and methyl sulfonyl methane [GCM]) nutraceutical supplements on female rat model of acute or chronic arthritis induced by bacterial outer membrane protein (OMP) from faecal flora of healthy and rheumatic humans. Anti-cyclic citrullinated peptide (anti-CCP2), C-reactive protein (CRP) and rheumatoid factor (RF) values increased (p < 0.05) in both arthritic groups as compared to normal values. The rheumatic markers anti-CCP2, CRP and RF values decreased significantly in E- and GCM-treated groups compared to arthritic none-treated acute or chronic groups. The results of RF values of GCM-treated groups in acute and chronic models decreased exhibiting no statistical difference compared with the normal value. Histological examinations of the hind paw sections revealed moderate inflammation, oedema and mild proliferation of synovial cells in acute arthritic rats and more damage to cartilage and bone with severe inflammation in chronic ones. Echinacea acute treated group showed edema with proliferated synovial membrane and partial damage in cartilage and bone. While in the E-chronic treated group, rough edge with destructed cartilage and bone existed. However, the acute GCM group revealed mild cartilage damage. But the chronic GCM group showed mild synovial cells proliferation and revealed no inflammation with mild cartilage damage edge. Results demonstrated the OMP arthropathic property and through promising light on arthritis treatment using E- or GCM, with the advantage of GMC results over that of E-. The composite GCM is needed for further studies over the dose and duration to assess its preventive effects against the bacterial OMP arthrogenicity.
21640047 Body composition phenotypes in systemic lupus erythematosus and rheumatoid arthritis: a co 2011 May OBJECTIVES: The amount and distribution of fat and lean mass have important implications for health and systemic inflammation may represent a risk for altered body composition. The aim of this study was to analyse whether changes in body composition are similarly associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), two inflammatory conditions of different pathogenesis. METHODS: Body mass index (BMI), waist circumference, fat mass (FM) and fat-free mass (FFM) were measured in 92 women with SLE, 89 with RA and 107 controls. Results were compared among the 3 groups and correlations of FM percentage were explored within SLE and RA. RESULTS: Abnormal body composition was more frequent in women with SLE and RA than in non-inflammatory controls, despite having a similar BMI. RA diagnosis was significantly associated with overfat (OR=2.782, 95%CI 1.470-5.264; p=0.002) and central obesity (OR=2.998, 95%CI 1.016-8.841; p=0.04), while sarcopenia was more common among SLE (OR=3.003; 95%CI 1.178-7.676; p=0.01). Sarcopenic obesity, i.e. the coexistence of overfat with sarcopenia, was present in 6.5% of SLE and 5.6% of RA women, but no controls. Independent correlations of FM percentage in women with SLE included smoking, disease activity and CRP. In RA, education, disease activity and cumulative corticosteroid dose were identified as independent predictors of FM percentage. CONCLUSIONS: Women with SLE or RA diagnosis are more likely to have abnormal body composition phenotype, with some differences existing between these two conditions. Changes in body composition are partly explained by the inflammatory burden of disease and its treatment.
21266503 Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis 2011 Apr 12 The efficacy of anti-TNF-α therapies highlights the role of TNF-α in the pathogenesis of rheumatoid arthritis (RA). However, the mechanism of action of these agents is poorly understood at the molecular level. The aim of this study was to characterize the effects of anti-TNF-α treatment on the global gene expression profile in peripheral blood mononuclear cells (PBMCs) of responder RA patients. Changes in gene expression were determined using oligonucleotide microarrays (25,341 genes) in PBMCs obtained before and after 12 wk of treatment with either etanercept or adalimumab from responder RA patients. Two hundred fifty-one genes displayed significant changes (false discovery rate < 0.1%) in expression level (178 upregulations with mean fold change = 1.5 and 73 downregulations with mean fold change = -1.50) after 12 wk of treatment. Importantly, the expression of several genes, including those coding for the calcium binding proteins S100A12 and A8, CD14 antigen, Selectin P, or ribosomal protein L39, reported to be upregulated in RA patients, were found to be decreased after anti-TNF-α treatment. Globally, inflammation, immune response, apoptosis, protein synthesis, and mitochondrial oxido-reduction were the most affected pathways in response to anti-TNF-α treatment. The obtained gene expression signature in PBMCs provides new information to better understand the mechanisms of action of anti-TNF-α treatment in RA patients.
22761714 High-sensitivity cardiac troponin-I is elevated in patients with rheumatoid arthritis, ind 2012 OBJECTIVES: We examined the hypothesis that cardiac-specific troponin-I (cTn-I), a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA). BACKGROUND: RA patients have an increased incidence of heart failure (HF). Chronic myocardial injury in RA may be a mechanism for the development of HF. METHODS: We compared cTn-I concentrations measured by high-sensitivity immunoassay in 164 patients with RA and 90 controls, excluding prior or active heart failure. We examined the relationship between cTn-I concentrations and cardiovascular risk factors, inflammation, and coronary artery calcium score (CACS), a measure of coronary atherosclerosis. RESULTS: cTn-I concentrations were 49% higher in patients with RA (median 1.15 pg/mL [IQR 0.73-1.92] than controls (0.77 pg/mL [0.49-1.28](P<0.001). The difference remained statistically significant after adjustment for demographic characteristics (P = 0.002), further adjustment for cardiovascular (CV) risk factors (P = 0.004), inflammatory markers (P = 0.008), and in a comprehensive model of CV risk factors and inflammatory markers (P = 0.03). In patients with RA, cTn-I concentrations were positively correlated with age (rho = 0.359), Framingham risk score (FRS) (rho = 0.366), and systolic blood pressure (rho = 0.248 (all P values ≤ 0.001)), but not with measures of inflammation or RA drug therapies. cTn-I was significantly correlated with CACS in RA in univariate analysis, but not after adjustment for age, race, sex and FRS (P = 0.79). Further model adjustments for renal function and coronary artery disease confirmed the significance of the findings. CONCLUSION: High-sensitivity cTn-I concentrations are elevated in patients with RA without heart failure, independent of cardiovascular risk profile and inflammatory markers. Elevated troponin concentrations in RA may indicate subclinical, indolent myocardial injury.
21532534 Associations between parameters of nutritional status and disease activity in patients wit 2011 Apr INTRODUCTION: In patients with rheumatoid arthritis (RA), the loss of body cell mass is observed, known as rheumatoid cachexia. Cachexia is associated with increased morbidity and premature mortality of RA patients. OBJECTIVES: The aim of the study was to assess the effect of chronic inflammation and disease activity on nutritional status in RA patients. PATIENTS AND METHODS: In 140 patients with RA (111 women, 29 men), RA activity was measured using the Disease Activity Score in 28 joints (DAS28) and using the Modified Health Assessment Questionnaire (M-HAQ). The nutritional status was assessed with the following parameters: serum albumin and total cholesterol (TC), body mass index (BMI), hand-grip strength (HGS), and tricipital skinfold thickness. RESULTS: There was a significant association between the parameters of nutritional status and the markers of inflammatory disease activity (number of swollen and tender joints, C-reactive protein, hemoglobin) and physical disability (M-HAQ). Swollen joint count and M-HAQ were inversely correlated with several nutritional parameters. In patients with high disease activity, significantly lower HGS and serum albumin levels were observed. Advanced stages of the disease (erosive and/or long-standing RA) were associated with lower HGS and higher TC levels. CONCLUSIONS: The nutritional status of RA patients is determined by the intensity of chronic inflammatory process observed in the course of the disease and by disease duration.
22992760 RING-finger type E3 ubiquitin ligase inhibitors as novel candidates for the treatment of r 2012 Dec Rheumatoid arthritis (RA) significantly affects quality of life. We recently cloned synoviolin, a RING-type E3 ubiquitin ligase implicated in the endoplasmic reticulum-associated degradation (ERAD) pathway. Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of RA. Inhibition of synoviolin activity is a potentially useful therapeutic approach for the treatment of RA. We conducted a high-throughput screen of small molecules to find inhibitors of synoviolin autoubiquitination activity. We identified two classes of small molecules, named LS-101 and LS-102, which inhibited synoviolin activity. LS-102 selectively inhibited synoviolin enzymatic activity, while LS-101 inhibited a broad array of RING-type E3 ligases. Moreover, these inhibitors suppressed the proliferation of rheumatoid synovial cells, and significantly reduced the severity of disease in a mouse model of RA. Our results suggest that inhibition of synoviolin is a potentially useful approach in the treatment of RA.
21572155 The influence of rheumatoid arthritis disease characteristics on heart failure. 2011 Aug OBJECTIVE: To examine the influence of rheumatoid arthritis (RA) characteristics and antirheumatic medications on the risk of heart failure (HF) in patients with RA. METHODS: A population-based incidence cohort of RA patients aged ≥ 18 years (1987 American College of Rheumatology criteria first met between January 1, 1980, and January 1, 2008) with no history of HF was followed until onset of HF (defined by Framingham criteria), death, or January 1, 2008. We collected data on RA characteristics, antirheumatic medications, and cardiovascular (CV) risk factors. Cox models adjusting for age, sex, and calendar year were used to analyze the data. RESULTS: The study included 795 RA patients [mean age 55.3 yrs, 69% women, 66% rheumatoid factor (RF)-positive]. During the mean followup of 9.7 years, 92 patients developed HF. The risk of HF was associated with RF positivity (HR 1.6, 95% CI 1.0, 2.5), erythrocyte sedimentation rate (ESR) at RA incidence (HR 1.6, 95% CI 1.2, 2.0), repeatedly high ESR (HR 2.1, 95% CI 1.2, 3.5), severe extraarticular manifestations (HR 3.1, 95% CI 1.9, 5.1), and corticosteroid use (HR 2.0, 95% CI 1.3, 3.2), adjusting for CV risk factors and coronary heart disease (CHD). Methotrexate users were half as likely to have HF as nonusers (HR 0.5, 95% CI 0.3, 0.9). CONCLUSION: Several RA characteristics and the use of corticosteroids were associated with HF, with adjustment for CV risk factors and CHD. Methotrexate use appeared to be protective against HF. These findings suggest an independent effect of RA on HF that may be further modified by antirheumatic treatment.
22059801 Measurement properties of physical function scales validated for use in patients with rheu 2011 Nov 7 BACKGROUND: The aim of this study was to systematically review the content validity and measurement properties of all physical function (PF) scales which are currently validated for use with patients with rheumatoid arthritis (RA). METHODS: Systematic literature searches were performed in the Scopus and PubMed databases to identify articles on the development or psychometric evaluation of PF scales for patients with RA. The content validity of included scales was evaluated by linking their items to the International Classification of Functioning Disability and Health (ICF). Furthermore, available evidence of the reliability, validity, responsiveness, and interpretability of the included scales was rated according to published quality criteria. RESULTS: The search identified 26 questionnaires with PF scales. Ten questionnaires were rated to have adequate content validity. Construct validity, internal consistency, test-retest reliability and responsiveness was rated favourably for respectively 15, 11, 5, and 6 of the investigated scales. Information about the absolute measurement error and minimal important change scores were rarely reported. CONCLUSION: Based on this literature review, the disease-specificHAQ and the generic SF-36 can currently be most confidently recommended to measure PF in RA for most research purposes. The HAQ, however, was frequently associated with considerable ceiling effects while the SF-36 has limited content coverage. Alternative scales that might be better suited for specific research purposes are identified along with future directions for research.
22994084 [The efficiency and safety of adalimumab treatment in patients with active rheumatoid arth 2012 AIM: To confirm the efficacy and safety of adalimumab (ADA) added to the standard antirheumatic therapy performed in patients with rheumatoid arthritis (RA) of moderate and high activities. SUBJECTS AND METHODS: The open-labeled multicenter study enrolled 100 adult patients (11 men, 89 women; mean age 50.9 +/- 11.1 years) with active RA according to the ACR criteria (1987) despite their treatment with disease-modifying antirheumatic drugs, the average number of which in the history was 2.1 per man. At baseline, DAS28 CRP was as many as 6.2 +/- 0.84 scores; C-reactive protein (CRP) was 37.1 +/- 34.7 mg/l. In accordance with the indications officially registered in the European Union and the Russian Federation, ADA was given in a dose of 40 mg 2 weeks. Before administration of the drug, every patient underwent screening examination for tuberculosis, which used a tuberculin test and chest X-ray. The screening covered a period of the treatment up to 24 weeks and its subsequent period within 70 days after administration of the last dose of ADA in order to study its safety. RESULTS: DAS28-CRP scores decreased from 6.14 +/- 0.86 (at baseline) to 3.39 +/- 1.1 (by the end of the study). At 12 weeks, 22% of the patients achieved a low RA activity (DAS28-CRP < or = 3.2 scores); 14% achieved clinical remission (DAS28-CRP < or = 2.6 scores); at 24 weeks, these were 37 and 25% of the patients, respectively. There were differences in effectiveness in terms of the baseline disease activity. At 24 weeks, ACR20, ACR50, and ACR 70 responses were achieved in 88, 67, and 26% of the patients, respectively. The HAQ functional index reduced from 1.9 +/- 0.6 (at baseline) to 1.081 +/- 0.64 (at 12 weeks) and 1.04 +/- 0.68 (at 24 weeks) scores. Twenty-four patients were recorded as having 40 adverse reactions (AR), including only one severe AR (septic arthritis). There were no cases of tuberculosis. CONCLUSION: The Russian multicenter study demonstrated the high clinical efficacy of ADA in patients with the moderate and high activity of RA unresponsive to standard therapy, as well as its satisfactory safety.
20799264 American College of Rheumatology hybrid analysis of certolizumab pegol plus methotrexate i 2011 Jan OBJECTIVE: The American College of Rheumatology (ACR) hybrid (a modified mean percent response to treatment) was officially recommended by the ACR as a revision to 20%, 50%, and 70% response criteria (ACR20/50/70) scores, but has not been tested in clinical trials. We performed a post hoc analysis of a phase III study of certolizumab pegol (Rheumatoid Arthritis Prevention of Structural Damage 1 [RAPID 1]) using the ACR hybrid. METHODS: Patients with active rheumatoid arthritis were randomized to certolizumab pegol (200 mg or 400 mg every other week) plus methotrexate or placebo plus methotrexate. ACR hybrid scores were compared with ACR20/50/70 outcomes. RESULTS: Differences between active treatment and placebo were significant throughout the study using the ACR20 and ACR hybrid outcomes. In the certolizumab pegol 200 mg group, the median ACR hybrid score at week 52 (last observation carried forward) was 49.99. A total of 258 (65.8%) of 392 and 172 (43.9%) of 392 patients had ACR20 and ACR50 responses, respectively. An additional 55 patients (14.0%) and 59 patients (15.1%) had mean improvements in ACR core measures of ≥ 20% and ≥ 50%, respectively, and therefore had positive ACR hybrid scores, despite lacking ACR20 and ACR50 responses, respectively. In the placebo group, median ACR hybrid scores were <10 at most time points; unlike other measures, the ACR hybrid measure indicated worsening scores for many patients. CONCLUSION: ACR hybrid analysis had greater sensitivity than traditional ACR20/50/70 criteria, demonstrating improvements in ACR20 nonresponders treated with certolizumab pegol. Negligible benefit was observed with placebo using ACR hybrid analysis.
22765310 Citrullinated vimentin stimulates proliferation, pro-inflammatory cytokine secretion, and 2012 Oct OBJECTIVES: We aimed to investigate the possible effects of vimentin (Vim) and citrullinated Vim (cVim) on proliferation capacity, pro-inflammatory cytokine secretion, and the expression of peptidylarginine deiminase type 4 (PADI4) and receptor activator of nuclear factor kappa B ligand (RANKL) in cultured fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. METHOD: Human native Vim was citrullinated with rabbit PAD in vitro and detected using a Western blot assay with anti-modified citrulline antibody (anti-MC Ab). FLSs from RA or OA synovial samples were stimulated with Vim or cVim. Cell proliferation capacity was determined using the Celltiter 96 AQueous cell proliferation assay. The concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The expression of PADI4 and RANKL was measured by real-time polymerase chain reaction (RT-PCR) and a Western blot assay. RESULTS: Our Western blot assay with anti-MC Ab indicated that the amount of cVim increased significantly after Vim had been incubated with rabbit PAD in vitro. The proliferation capacity and secretion of TNF-α and IL-1 were significantly enhanced in the FLSs of RA patients when treated with cVim. However, when treated with Vim, an inhibitory effect on the proliferation capacity was noted in the FLSs from RA and also from OA patients. cVim significantly increased the expression of PADI4 and RANKL in the FLSs from RA patients. CONCLUSION: cVim seems to have remarkable biological effects on RA as confirmed by the stimulation of proliferation capacity, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression in the FLSs of RA patients.
21898275 [Autoimmune pancreatitis associated with rheumatoid arthritis: successful combination ther 2011 Sep MEDICAL HISTORY AND CLINICAL FINDINGS: A 70-year-old female patient suffered from steatorrhea and upper abdominal discomfort for 8 weeks combined with new onset of arthralgia in both hands. Additionally she reported elevated fasting blood glucose levels. The physical examination was without pathological findings except for mild upper abdominal pressure pain. INVESTIGATIONS: Imaging studies, including MRI and ultrasound examinations showed diffuse pancreatic enlargement without peripancreatic vessel involvement. Serological examinations showed elevated Cancer Associated Antigen 19 - 9 (1289 U/ml) and hyperglobulinemia with an IgG level of 170 mg/dl. The inflammatory markers were within normal ranges other than a slightly elevated erythrocyte sedimentation rate (35mm/1 h). Subsequent pancreatic biopsy showed lymphoplasmocellular, neutrophile and eosinophile granulocyte infiltration causing damage of the acinar pancreatic cells, typical for autoimmune pancreatitis (AIP). Magnetic resonance imaging (MRI) confirmed arthritis of both hands. TREATMENT AND COURSE: Medical treatment was started with oral prednisolone (50 mg/day) for one week, tapered to 25 mg/day for another 2 weeks, followed by dose reductions of 5 mg/day every 2 weeks with a final maintenance dose of 5 mg/day for 8 months. After the first week of steroid therapy methotrexate (MTX) was started with an initial dose of 10 mg/week. Dose was raised until a final dosage of 30 mg/week. After 8 months without relapse, the maintenance therapy was reduced to 20 mg/week MTX and corticosteroids were stopped. CONCLUSION: With this treatment regimen the patient has showed complete remission of AIP and arthritis for 36 months. MTX may be successful as an initial basic treatment to reach better control of autoimmune-related extrapancreatic manifestations.
23078808 Overview and analysis of treat-to-target trials in rheumatoid arthritis reporting on remis 2012 Jul OBJECTIVES: To present an updated overview of tight control studies with a fixed treatment target ('treat-to-target'), reporting on (sustained) remission in rheumatoid arthritis (RA). METHODS: A search of the electronic databases Medline (PubMed), Embase and Cochrane was performed in July 2012 to identify trials and studies addressing tight control with treat-to-target reporting on (sustained) remission, regardless of definition or duration. Next to a narrative overview of the identified studies, a formal meta-analysis was performed pooling study results of studies comparing the effects of a tight control and treat-to-target strategy arm with those of a usual care strategy. RESULTS: Thirteen studies were found, 4 comparing effects of tight control to those of usual care, 1 comparing the effects of 2 strategies with the same DMARDs but using different treatment targets, and 8 comparing the effects of tight control strategies with different DMARDs but with the same treatment target. Remission rates differed over a wide range in these studies, but in general were not higher in studies applying a biological DMARD from start compared to studies with initial conventional DMARD strategies. The meta-analysis of the 4 studies comparing tight control versus usual care shows that applying a treat to (any) target strategy appeared to approximately double the remission rates of the participating early RA patients. CONCLUSIONS: The trials comparing tight control arms show in general that the more intensive the strategy, the more strict the treatment aim and the more tight the tight control, the better the remission rates. It does not appear obligatory to start with a biological DMARD to get good results in tight control studies.
22247351 IgG glycosylation changes and MBL2 polymorphisms: associations with markers of systemic in 2012 Mar OBJECTIVE: To examine whether IgG glycosylation changes and MBL2 genotypes are associated with systemic inflammation and joint destruction in rheumatoid arthritis (RA). METHODS: IgG N-glycan content was determined from serum in 118 patients with RA by high-throughput glycan analysis using normal-phase high-pressure liquid chromatography. MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) were determined. Systemic inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Joint destruction was assessed by total Sharp score (TSS) and alloplastic surgery records. RESULTS: IgG hypogalactosylation was significantly correlated to IL-6 (Spearman's rho = 0.32, p < 0.001), CRP (Spearman's rho = 0.31, p < 0.001), TSS (Spearman's rho = 0.25, p = 0.01), and alloplastic replacement of joints (Spearman's rho = 0.18, p = 0.05). In multivariate analysis including age, CRP, anticitrullinated protein antibodies (ACPA), and other confounders, IgG hypogalactosylation was significantly associated with TSS (p = 0.014) and alloplastic joint replacement (OR 76.5, p = 0.041) in patients homozygous for the high expression MBL2 genotype YA/YA, but not in carriers of lower expression genotypes. CONCLUSION: Decreased galactosylation of IgG correlated to markers of inflammation, i.e., IL-6 and CRP. Only in patients homozygous for high expression of the MBL2 genotype YA/YA was IgG hypogalactosylation associated with markers of joint destruction. Our results suggest that inflammation-associated decreased galactosylation of IgG combined with high expression MBL2 genotypes are involved in the pathophysiology of RA.