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ID PMID Title PublicationDate abstract
27311178 [Rheumatoid arthritis and cytokines]. 2016 Jun The cytokines are an important substance involved in the immune reaction and maintenance of homeostasis. An imbalance in the cytokine network may lead to inflammation and autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoimmune and systemic inflammatory disorder characterized by synovial inflammation, destruction of cartilage and bone and systemic manifestations. The pro-inflammatory cytokines such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), IL-6 and IL-17 induce the inflammation of the joints and destruction of bone and cartilage via activation of macrophages, fibroblast like synoviocytes (FLS), helper T (Th) cells and osteoclasts. Recently, the available therapeutic agents that target these cytokines have excellent clinical effects in RA patients.
27777170 Rheumatoid arthritis, insulin resistance, and diabetes. 2017 Jul Recent progress in the management of rheumatoid arthritis (RA) is turning attention toward comorbidities, such as diabetes. The objectives of this review are to clarify the links between RA and diabetes and to assess potential effects of disease-modifying antirheumatic drugs (DMARDs) on diabetes. The increased insulin resistance seen in RA is closely linked to the systemic inflammation induced by certain proinflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-6. The prevalence of type 2 diabetes is increased in patients with RA. Furthermore, certain DMARDs including hydroxychloroquine, methotrexate, TNFα antagonist, and interleukin-1β antagonists seem to improve the markers of glucose metabolism. In contrast, glucocorticoids tend to adversely affect glycemic control, particularly when taken chronically. Consequently, a crucial yet insufficiently applied rule is that cardiovascular risk factors must be sought and treated routinely, particularly as the choice of the DMARD may affect glucose metabolism.
25782118 Chronic inhibition of tumor necrosis factor-α with infliximab improves myocardial deforma 2015 Mar OBJECTIVES: This study investigated the effects of infliximab, a monoclonal antibody against TNFα, on myocardial deformation and aortic elasticity in patients with rheumatoid arthritis (RA), and the association of aortic elasticity with myocardial deformation. STUDY DESIGN: 38 female rheumatoid arthritis (RA) patients and 30 healthy controls were included in the study. Twenty patients received infliximab and 18 patients received prednisolone. Left ventricular (LV) longitudinal, circumferential and radial strain, systolic strain rate and early diastolic strain rate using speckle-tracking echocardiography, and aortic elasticity using M-mode echocardiography were assessed at baseline and post-treatment. RESULTS: LV systolic longitudinal basal-, mid-, and apical strain, systolic mid- and apical strain rate, basal-, mid- and apical early strain rate, circumferential systolic apical strain and systolic strain rate were reduced in RA patients compared to controls. Compared to baseline, infliximab treatment increased aortic strain, aortic distensibility and decreased aortic ß index. No significant aortic elastic changes were observed with prednisolone treatment. Longitudinal basal- and apical strain, basal-, mid- and apical systolic and diastolic strain rates, circumferential basal systolic strain, radial mid- and apical strain and apical strain rate were increased following infliximab treatment. Infliximab treatment improves aortic elasticity in parallel to myocardial deformation, but no significant association was observed following prednisolone treatment. CONCLUSION: Myocardial deformation is impaired in RA patients and is related to aortic stiffness. Chronic inhibition of TNFα improves LV deformation in association with aortic elasticity.
26060323 Estimating the diagnostic accuracy of rheumatoid factor in UK primary care: a study using 2015 Oct OBJECTIVE: To investigate the diagnostic accuracy of RF as a test for RA in primary care and its impact on referral times using the Clinical Practice Research Datalink. METHODS: We identified all patients with a first RF test recorded in the Clinical Practice Research Datalink between 1 January 2000 and 31 December 2008 and those diagnosed with RA within 2 years of testing. We calculated likelihood ratios (LRs), sensitivity, specificity and predictive values of RF for a diagnosis of RA. We compared time to hospital referral in those testing positive and negative using Kaplan-Meier failure curves and log-rank tests. RESULTS: Of 62 436 first RF tests, 4679 (7.5%) were positive. There were 1753 incident cases of RA, of which 57.8% were seropositive. The positive LR for RF was 9.5 (95% CI 9.0, 10.0) and the negative LR was 0.5 (95% CI 0.4, 0.5). Sensitivity and specificity were 57.8% (95% CI 55.4%, 60.1%) and 93.9% (95% CI 93.7%, 94.1%) and the positive predictive value and negative predictive value were 21.4% (95% CI 20.3%, 22.6%) and 98.7% (95% CI 98.6%, 98.8%), respectively. Median time to first hospital contact after the first RF test in those with seropositive vs seronegative results was 54 days (95% CI 49, 58) vs 150 (95% CI 147, 152). CONCLUSION: Only 2.8% of patients undergoing RF testing were diagnosed with RA, suggesting that RF is used to screen patients with musculoskeletal symptoms rather than those with more specific features of RA. A positive RF test may be helpful in diagnosing RA in primary care but performs badly in excluding RA and may delay referral.
27024887 [RETROSPECTIVE DATA ANALYSIS OF THE PATIENTS WITH INFLAMMATORY JOINT DISEASES TREATED WITH 2015 Golimumab is a human monoclonal antibody which inhibits tumor necrosis factor-alpha (TNF-α) and is approved for the treatment of inflammatory arthritides (rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis) when the conventional non-pharmacological and pharmacological therapies fail to cause remission or low disease activity. In this retrospective study there were included patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis who were treated in Croatia with golimumab, from June 2011 to June 2013. included and these retrospective data are compared with similar data from clinical trials and other available databases. Standard variables of disease activity and functional ability were observed. Results demonstrated significant efficacy of golimumab regarding lowring the disease activity and imrpving functional ability in pateints with these inflammatory rherumatic disease. In conclusion, in this retrospective study during two years treatment golimumab showed efficacy in decreasing disease activity and imrpove functional ability in patiemts with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.
26551381 Recommendations for assessing and preventing falls in adults of all ages with rheumatoid a 2015 Nov Rheumatoid arthritis (RA) is a debilitating disease that affects younger as well as older adults. It is associated with a high risk of injurious falls due to problems such as lower-limb muscle weakness, balance impairment, swollen and tender joints, pain, and fatigue. Falls are typically associated with older people; hence, many professionals do not recognise the risks for younger persons with diseases such as RA. Falls can lead to devastating consequences, such as fatalities, hip fractures (with 50% of those affected never regaining their previous level of mobility and 30% dying within 1 year), or loss of independence and confidence. Research has shown that many people are either unaware or deny their risk of falling. Therefore, it is important that health professionals, such as community nurses, are aware of the risk factors, methods of assessment, and evidence-based preventative measures, so that falls can be avoided in this population. This article presents research and practice implications for community nurses to enable them to assess, treat, and appropriately refer adults with RA who are also at risk of falls.
27736747 Rheumatoid arthritis: identifying and characterising polymorphisms using rat models. 2016 Oct 1 Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans.
26406605 Elevated Membrane and Soluble CD64: A Novel Marker Reflecting Altered FcγR Function and D 2015 OBJECTIVES: Fc receptors (FcR) interacting with immune complexes (ICs) is a central event in the immune pathogenesis of rheumatoid arthritis (RA). Here we asked if a specific FcR is linked to RA pathogenesis and if FcR activities relate to disease and treatment outcome in early RA. MATERIAL AND METHODS: Twenty autoantibody-positive RA patients and 33 HC were included. The patients were evaluated before and after treatment with methotrexate and prednisolone. At follow-up, the EULAR response criteria were applied to determine the individual treatment outcomes. Serum immunoglobulin levels were measured and the expression of FcR for IgG (FcγR) and IgA (FcαR) on peripheral blood monocytes were determined by flow cytometry. The monocytic FcγR function was evaluated by human IgG1 and IgG3 IC-binding and TNFα stimulated release. Plasma levels of soluble FcRs (sFcRs) were determined with ELISA. RESULTS: The IgG1 and IgG3 levels were elevated in the RA sera. The RA monocytes expressed more CD64 and cell surface-bound IgG than HC monocytes, and showed an impaired FcγR function as reflected by changes in IC-binding and decreased IC-stimulated TNFα secretion. These findings correlated significantly with different disease activity markers. Furthermore, sFcRs were elevated in the patient plasma, and sCD64 was specific for RA (compared with a reference group of patients with active psoriatic arthritis). Following treatment, immunoglobulins and sFcR levels were reduced, whereas membrane CD64 was only decreased in patients with good response to treatment. CONCLUSIONS: Early RA patients display increased membrane and soluble CD64 and an impaired FcγR function correlating with joint disease activity. Beneficial responses of anti-rheumatic treatment in patients reduce CD64. These data suggest sCD64 as an important objective biomarker in RA.
26493042 Effect of acute and chronic glucocorticoid therapy on insulin sensitivity and postprandial 2016 Apr OBJECTIVE: Postprandial hyperglycaemia is associated with increased arterial stiffness and cardiovascular events. Low-dose prednisolone causes insulin resistance that typically manifests as postprandial hyperglycaemia. We investigated whether prednisolone causes postprandial vascular dysfunction in a cohort of patients with rheumatoid arthritis. DESIGN: An open interventional and cross-sectional study was undertaken. PATIENTS AND MEASUREMENTS: Eighteen subjects with rheumatoid arthritis who had not taken oral glucocorticoids for ≥6 months were studied before and after prednisolone 6 mg/day for 7 days to determine the acute effects of prednisolone. Pre-prednisolone data were compared to 18 subjects with rheumatoid arthritis taking long-term (>6 months) prednisolone (6·5 ± 1·8 mg/day) to assess the chronic effects of prednisolone. Augmentation index (by applanation tonometry) and reactive hyperaemia index (by peripheral artery tonometry) were measured before and after a mixed-meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). Insulin sensitivity was estimated by the Matsuda index and sympathetic nervous system activity from urinary noradrenaline excretion. RESULTS: Matsuda index was lower after acute (2·0 ± 1·0 vs 3·6 ± 1·1, P = 0·01) and chronic (1·9 ± 1·0 vs 3·6 ± 1·1, P = 0·04) prednisolone. Postprandial augmentation index was lower after acute prednisolone (2551 ± 197 vs 2690 ± 272%*min, P ≤ 0·001), but not chronic prednisolone. There were no significant differences in reactive hyperaemia index with acute or chronic prednisolone. Noradrenaline excretion was lower after acute (54 ± 8 vs 93 ± 23 nmol/6 h, P = 0·02), but not chronic, prednisolone. CONCLUSIONS: Prednisolone-induced insulin resistance is not associated with postprandial vascular dysfunction in patients with rheumatoid arthritis. Reduced sympathetic activity may contribute to the reduction in postprandial arterial stiffness with acute prednisolone.
24589014 Changes in peripheral blood B cell subsets at diagnosis and after treatment with disease-m 2015 May OBJECTIVE: To assess variation in peripheral blood B lymphocyte subsets in rheumatoid arthritis (RA). METHODS: B lymphocyte subsets in disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA (n = 30), patients with RA treated with DMARDs (n = 73) and healthy controls (n = 46) were analyzed by flow cytometry. Total B cells, total memory B cells, immunoglobulin M (IgM) memory B cells, switched memory B cells, non-switched memory B cells, CD21lo B cells, transitional B cells and plasmablasts were measured. Correlation with clinical and laboratory parameters was performed. RESULTS: Total memory B cells, IgM memory B cells and non-switched memory B cells were reduced in RA patients at diagnosis compared to controls (P < 0.05). In patients with treated RA, there was a further reduction of total B cells, CD21lo cells, transitional B cells and plasmablasts, compared to controls (P < 0.05). The reduction in absolute numbers of total B cells, switched memory B cells, CD21lo cells, transitional B cells and plasmablasts in treated RA patients was significant (P < 0.05) even when compared to the DMARD-naïve patients. Only treatment responders (Disease Activity Score < 3.2) had reduced total B cells and absolute numbers of switched and IgM memory B cells (P < 0.05). In patients requiring leflunomide, total memory B cells, IgM memory B cells, non-switched memory B cells and absolute numbers of switched memory B cells were reduced compared with the remainder of the patient group (P < 0.05). CONCLUSION: There is reduction of various B cell subsets in RA patients at diagnosis. Treatment with DMARDs leads to further reduction in additional B cell subsets without correction of the abnormalities. Reduction in individual subsets may predict RA patients requiring more intensive therapy.
27450561 Tumor necrosis factor alpha, citrullination, and peptidylarginine deiminase 4 in lung and 2016 Jul 22 BACKGROUND: The relationship between lung and joint inflammation in rheumatoid arthritis is poorly understood. Lung inflammation with resultant protein citrullination may trigger anti-citrullinated protein antibodies, inflammation, and arthritis. Alternatively, lung and joint inflammation may be two manifestations of a single underlying pathology. The lung has increased citrullination and TNF-α levels are high in rheumatoid arthritis; however, it is unknown if TNF-α can induce lung protein citrullination. The citrullinating enzyme peptidylarginine deiminase 4 (PAD4) exacerbates TNF-α-induced arthritis, but a role for PAD4 in lung citrullination and TNF-α-induced lung inflammation has not been explored. Our aim was to use TNF-α-overexpressing mice to clarify the intersection of TNF-α, citrullination, PAD4, arthritis, and lung inflammation. METHODS: Lung protein citrullination in wild-type mice, mice that overexpress TNF-α systemically (TNF(+)), TNF(+)PAD4(+/+), and TNF(+)PAD4(-/-) mice was quantified by both gel electrophoresis using a citrulline probe and western blot. Hematoxylin and eosin (H&E)-stained lung sections from TNF(+)PAD4(+/+) and TNF(+)PAD4(-/-) mice were scored for lung inflammation. H&E-stained ankle joint sections from mice that overexpress TNF-α only in the lungs were assessed for arthritis. RESULTS: TNF(+) mice have increased lung protein citrullination. TNF(+)PAD4(-/-) mice do not have significantly reduced lung protein citrullination, but do have decreased lung inflammation compared to TNF(+)PAD4(+/+) mice. Mice that overexpress TNF-α only in the lungs do not develop arthritis. CONCLUSIONS: PAD4 exacerbates lung inflammation downstream of TNF-α without having a major role in generalized protein citrullination in inflamed lungs. Also, TNF-α-induced lung inflammation is not sufficient to drive murine arthritis.
25802424 The effects of compression gloves on hand symptoms and hand function in rheumatoid arthrit 2016 Mar OBJECTIVE: to evaluate the effects of compression gloves in adults with rheumatoid arthritis and hand osteoarthritis. DATA SOURCES: Systematic review of randomized controlled trials identified from MEDLINE, CINAHL, AMED, PEDro, OT Seeker, The Cochrane Library, ISI Web of Knowledge, Science Direct and PubMed from their inceptions to January 2015. REVIEW METHODS: Methodological quality of identified trials was evaluated using the PEDro scale by three independent assessors. Effects were summarized descriptively. RESULTS: Four trials (n=8-24; total n=74), comparing night wear of full-length finger compression gloves with placebo gloves, were assessed. Three were of moderate (PEDro score 4-5) and one low (score 3) methodological quality. Effect sizes or standardized mean differences could not be calculated to compare trials due to poor data reporting. In rheumatoid arthritis, finger joint swelling was significantly reduced, but results for pain and stiffness were inconclusive and no differences in grip strength and dexterity were identified. One study reported similar effects in pain, stiffness and finger joint swelling from both compression and thermal placebo gloves. Only one study evaluated gloves in hand osteoarthritis (n=5) with no differences. CONCLUSIONS: All the trials identified were small with a high risk of Type I and II errors. Evidence for the effectiveness of compression gloves worn at night is inconclusive in rheumatoid arthritis and hand osteoarthritis.
27513931 Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients wit 2016 BACKGROUND: Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an "angiogenic disease" because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA. OBJECTIVES: The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA. METHODS: 581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA. RESULTS: The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was lower than the number of women with wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher in RA patients than in control groups (both p = 0,0001). CONCLUSION: Present findings indicated that VEGF genetic polymorphism as well as VEGF protein levels may be associated with the susceptibility to RA in the Polish population.
25673155 Resurfacing shoulder arthroplasty for the treatment of severe rheumatoid arthritis: outcom 2015 Jun BACKGROUND AND PURPOSE: There is no consensus on which type of shoulder prosthesis should be used in patients with rheumatoid arthritis (RA). We describe patients with RA who were treated with shoulder replacement, regarding patient-reported outcome, prosthesis survival, and causes of revision, and we compare outcome after resurfacing hemi-arthroplasty (RHA) and stemmed hemi-arthroplasty (SHA). PATIENTS AND METHODS: We used data from the national Danish Shoulder Arthroplasty Registry and included patients with RA who underwent shoulder arthroplasty in Denmark between 2006 and 2010. Patient-reported outcome was obtained 1-year postoperatively using the Western Ontario Osteoarthritis of the Shoulder index (WOOS), and rates of revision were calculated by checking revisions reported until December 2011. The patient-reported outcome of RHA was compared to that of SHA using regression analysis with adjustment for age, sex, and previous surgery. RESULTS: During the study period, 167 patients underwent shoulder arthroplasty because of rheumatoid arthritis, 80 (48%) of whom received RHA and 34 (26%) of whom received SHA. 16 patients were treated with total stemmed shoulder arthroplasty (TSA), and 24 were treated with reverse shoulder arthroplasty (rTSA). 130 patients returned a completed questionnaire, and the total mean WOOS score was 63. The cumulative 5-year revision rate was 7%. Most revisions occurred after RHA, with a revision rate of 14%. Mean WOOS score was similar for RHA and for SHA. INTERPRETATION: This study shows that shoulder arthroplasty, regardless of design, is a good option in terms of reducing pain and improving function in RA patients. The high revision rate in the RHA group suggests that other designs may offer better implant survival. However, this should be confirmed in larger studies.
29071928 [Medicinal-powder-separated Long-snake Moxibustion over the Governor Vessel with Different 2016 Aug 25 OBJECTIVE: To observe the curative effect of herbal-medicine -powder-separated "Long-snake moxibustion" over the Governor Vessel at different vesiculation conditions in the treatment of rheumatoid arthritis (RA). METHODS: A total of 120 RA patients received herbal-powder-separated long-snake moxibustion in the present study and randomized into Banmao (Cantharides, CANT, being able to promote skin vesiculation for enhancing the therapeutic effect)-0 g group, CANT-1.5 g group and CANT-3.0 g group (n=40 in each group) according to the dosage of CANT used in the herbs-medicinal powder. In addition to Cantharides, the medicinal powder also contained Shexiang (Moschus, 1 g), Dingxiang (Flos Caryophylli,1 g) and Rougui (Cinnamon bark,1 g). When treated, the patient was asked to take a prone position, the ginger juice was evenly smeared on the patient's back from Dazhui (GV 14) to Yaoshu (GV 2, about 3 cm wide), then, the above-mentioned medicinal powder was spread on the smeared ginger juice, followed by putting a layer of gauze, ginger powder and ignited moxa-stick, respectively. The treatment was conducted once every 30 days, and twice altogether. The visual analog scale (VAS) was used to assess the pain seve-rity of moxibustion-induced skin vesiculation on the patient's back in 24 h after moxibustion. The severity of vesiculation was assessed according to the status of vesicles appeared at the local skin (0 point:no vesicles;3 points:string-of-beads-like vesicles with the vesicle diameter being less than 2 cm; 6 points:foliated vesicles with the vesicle diameter being larger than 2 cm). The patient's symptoms and dysfunction of hand-knee joints were scored, and serum rheumatoid factor (RF), C-reactive protein (CRP), immune globulin IgM and IgG contents were assayed by ELISA, and the erythrocyte sedimentation rate (ESR) was determined by using Westergren method. RESULTS: After moxibustion, of the three 40 RA patients in the CANT-0 g, CANT-1.5 g and CANT-3.0 g groups, 0, 10 and 12 cases were under control in their symptoms, 7, 16 and 19 experienced marked improvement, 17, 9 and 6 were improved, 16, 5 and 3 failed in the treatment, with the effective rates being 60.0%(16/40), 87.5%(35/40) and 92.5%(37/40), respectively. The curative effects of CANT-1.5 g and CANT-3.0 g were significantly superior to that of CANT-0 g (P<0.01). Both the scores for skin vesiculation status and pain severity were significantly higher in the CANT-3.0 g group than in the CANT-0 g (no skin vesiculation) and CANT-1.5 g groups, and markedly higher in the CANT-1.5 g group than in the CANT-0 g group (P<0.01). Following the treatment, the symptom score and joint dysfunction score, ESR level, and serum RF, CRP, IgM and IgG contents were considerably decreased in the three groups in comparison with pre-treatment in the same one group (P<0.01); and those of the CANT-1.5 g and CANT-3.0 g groups were markedly lower than those of CANT-0 g group (P<0.01). In addition, CANT-3.0 g was notably superior to CANT-1.5 g in lowering symptom and joint dysfunction scores, ESR, serum RF and CRP contents (P<0.05). No significant differences were found between the CANT-1.5 g and CANT-3.0 g groups in serum IgM and IgG levels and in the therapeutic effect (P>0.05). CONCLUSIONS: Long-snake moxibustion combined with CANT-induced vesiculation has a good curative effect in the treatment of RA, which may be associated with its effects in lo-wering ESR level, and serum RF, CRP, IgM and IgG contents. The curative effect of vesiculation moxibustion is far better than non-vesiculation moxibustion, but mild vesiculation moxibustion is recommended due to severe pain of CANT-3.0 g.
27245339 Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid 2016 Jun 1 Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.
26179634 Ulcerative keratitis in patients with rheumatoid arthritis in the modern biologic era: a s 2017 Feb AIM: To assess the prevalence, clinical characteristics, treatment, and outcomes of patients who developed ulcerative keratitis (UK) during the course of rheumatoid arthritis (RA) in the modern biologic era. METHOD: We retrospectively reviewed the medical records of 589 patients with RA who visited our department between April 2003 and October 2014, and identified patients who developed UK. We also obtained data about clinical characteristics of RA and UK, complications, treatment, and both visual and life prognoses of these patients. RESULTS: Among 589 patients with RA, eight patients (1.4%) were diagnosed with UK. The mean age at the onset of RA was 61.0 years, while the mean age at the onset of UK was 73.0 years. Most of the patients were seropositive and had established RA with a relatively low disease activity. Secondary Sjögren's syndrome was observed in two patients. Peripheral UK occurred as a complication of scleritis, while central UK was not associated with scleritis. Although the mean duration of follow-up was only 3.7 years, visual and life prognoses were both tolerable with therapy, including the use of topical and systemic corticosteroids and calcineurin inhibitors, sometimes combined with biologic disease-modifying antirheumatic drugs (DMARDs) and corneal transplantation. CONCLUSION: This retrospective study demonstrated that the prevalence of UK in patients with RA was 1.4%. Immediate combination therapy, including topical and systemic corticosteroids and calcineurin inhibitors, together with biologic DMARDs and corneal transplantation, was effective for treating RA patients who developed UK in the modern biologic era.
27369647 Ultrasound can be useful to predict an evolution towards rheumatoid arthritis in patients 2017 May INTRODUCTION: Ultrasound (US) subclinical synovitis in prerheumatoid arthritis (RA) patients has been demonstrated in anticitrullinated antibodies (ACPA) positive patients to be predictive for future development of RA. The aim of the study was to assess the value of the US as a predictive factor for the future development of RA in patients with polyarthralgia without ACPA. METHOD: Eighty consecutive ACPA-patients with polyarthralgia without clinical synovitis or ACPA before the US examination were included. To detect significant US synovitis, we applied the criteria of a US score (SONAR) validated among RA patients and controls. The diagnosis of RA was based on the ACR/EULAR criteria. RESULTS: Significant US synovitis were present at baseline in 20 (25%) of the patients. The mean (SD) follow-up time was 18 (7) months in both groups. Seven (9%) patients developed a clear RA and 2 another inflammatory arthritis. US synovitis at baseline was significantly associated with evolution to RA: 5/20 (25%) versus 2/60 (3%) (P<0.05). The free time to RA was significantly shorter when US synovitis were present (P<0.01). Moreover, after multivariate analysis, US appeared to be the only independent predictor of an evolution to RA (OR: 7.4). Results remained similar after including all patients developing another inflammatory arthritis. CONCLUSIONS: Our study suggests that US can be used as a predictor for the evolution to RA or other inflammatory arthritis in patients presenting polyarthralgia without ACPA.
26560845 Immunogenicity of anti-TNF biologic agents in the treatment of rheumatoid arthritis. 2016 INTRODUCTION: The use of biologic disease-modifying anti-rheumatic drugs (DMARDs), including therapeutic antibodies, antibody fragments and protein constructs that target key mediators in the pathophysiology of rheumatoid arthritis (RA), has improved the chance of achieving low disease activity and clinical remission. However, individual patients respond differently to biologic DMARD therapy, particularly the tumor necrosis factor (TNF) inhibitors. AREAS COVERED: While the variation of clinical response may be related to pharmacogenetic and other unknown factors, immunogenicity associated with some of these agents may contribute in part to a lack of efficacy and immune-mediated side effects. Timely detection of immunogenicity may avoid continued administration of ineffective treatment, and reduce unnecessary risks and costs. Access to and appropriate implementation of clinically validated drug level assays is required. EXPERT OPINION: There are currently no evidence-based recommendations to guide biologic therapy on the basis of drug level and immunogenicity testing but as more data become available and better tests are developed, a strategy of immunopharmacologic guidance to individualize treatment of RA will emerge. The potential benefits of this approach must be balanced against the costs of monitoring, and further research is required.
25302481 Disease-modifying antirheumatic drug use and the risk of incident hyperlipidemia in patien 2015 Apr OBJECTIVE: To compare the risk of incident hyperlipidemia in early rheumatoid arthritis (RA) patients after initiation of various disease-modifying antirheumatic drugs (DMARDs). METHODS: We conducted a cohort study using insurance claims data (2001-2012) in early RA patients. Early RA was defined by the absence of any RA diagnosis or DMARD prescriptions for 12 months. Four mutually exclusive groups were defined based on DMARD initiation: tumor necrosis factor α (TNFα) inhibitors ± nonbiologic (nb) DMARDs, methotrexate (MTX) ± nonhydroxycholorquine nbDMARDs, hydroxychloroquine ± non-MTX nbDMARDs, and other nbDMARDs only. The primary outcome was incident hyperlipidemia, defined by a diagnosis and a prescription for a lipid-lowering agent. For the subgroup of patients with laboratory results available, change in lipid levels was assessed. Multivariable Cox proportional hazard models and propensity score (PS) decile stratification with asymmetric trimming were used to control for confounding. RESULTS: Of the 17,145 early RA patients included in the study, 364 developed incident hyperlipidemia. The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) for hyperlipidemia were 1.41 (95% CI 0.99, 2.00) for TNFα inhibitors, 0.81 (95% CI 0.63, 1.04) for hydroxychloroquine, and 1.33 (95% CI 0.95, 1.84) for other nbDMARDs compared with MTX in the full cohort, while HRs for the PS trimmed cohort were 1.18 (95% CI 0.80, 1.73), 0.75 (95% CI 0.58, 0.98), and 1.41 (95% CI 1.01, 1.98), respectively. In the subgroup analysis, hydroxychloroquine use showed significant reduction in low-density lipoprotein (-8.9 mg/dl, 95% CI -15.8, -2.0), total cholesterol (-12.3 mg/dl, 95% CI -19.8, -4.8) and triglyceride levels (-19.5 mg/dl, 95% CI -38.7, -0.3) from baseline compared with MTX. CONCLUSION: Use of hydroxychloroquine may be associated with a lower risk of hyperlipidemia among early RA patients.