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ID PMID Title PublicationDate abstract
27572279 Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients v 2016 Oct The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic potential. The number of tartrate‑resistant acid phosphatase‑positive osteoclasts differentiated from PBMCs isolated from patients with RA was significantly increased compared with that of the healthy controls. In addition, the osteoclast number in patients with RA was correlated with the clinical indicators, Sharp score (r=0.810; P=0.001) and lumbar T‑score (r=‑0.685; P=0.014). Furthermore, the resorption area was increased in the RA group compared with the healthy controls. The mRNA and protein expression levels in PBMC‑derived osteoclasts treated with curcumin were measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Curcumin inhibited the osteoclastogenic potential of PBMCs, potentially by suppressing activation of extracellular signal‑regulated kinases 1 and 2, p38 and c‑Jun N‑terminal kinase, and inhibiting receptor activator of nuclear factor κB (RANK), c‑Fos and nuclear factor of activated T cells (NFATc1) expression. The results of the present study demonstrated that curcumin may inhibit the osteoclastogenic potential of PBMCs from patients with RA through the suppression of the mitogen‑activated protein kinase/RANK/c‑Fos/NFATc1 signaling pathways, and that curcumin may be a potential novel therapeutic agent for the treatment of bone deterioration in inflammatory diseases such as RA.
27315340 Serum and synovial fluid concentrations of cold-inducible RNA-binding protein in patients 2018 Jan AIM: There is growing evidence that cold-inducible RNA-binding protein (CIRP) promotes inflammatory responses. This study investigated the relationship between CIRP and rheumatoid arthritis (RA). METHODS: Peripheral blood and synovial fluid were collected from 15 patients with RA and from 16 patients with osteoarthritis (OA). The concentration of CIRP was measured with the sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of serum CIRP was significantly elevated in the RA patient group (RA patients = 26.39 ± 10.48 pg/mL, OA patients = 17.14 ± 7.24 pg/mL, P = 0.009). Furthermore, the RA patient group had a significantly higher CIRP concentration than that of the OA patient group in synovial fluid (153.56 ± 108.93 pg/mL vs. 23.63 ± 16.18 pg/mL, P < 0.001). The mean synovial fluid concentration of CIRP was significantly higher than that of the serum concentration in the RA patient group (serum concentration = 26.39 ± 10.48 pg/mL, synovial fluid = 153.56 ± 108.93 pg/mL, P < 0.001). Disease Activity Score of 28 joints (DAS28)-ESR (erythrocyte sedimentation rate) and DAS28-CRP (C-reactive protein) were positively correlated with the synovial fluid concentration of CIRP (DAS28-ESR: r = 0.582, P = 0.023; DAS28-CRP: r = 0.541, P = 0.037). CONCLUSION: The serum and synovial concentrations of CIRP in the RA patients were increased compared to the OA patients. Additionally, the synovial concentration of CIRP in RA patients correlated well with disease activity, that is, the DAS28-ESR/CRP. Based on these results, CIRP mediates inflammation and is a potential marker for synovial inflammation.
26636507 Do urban and rural residents living in Poland differ in their ways of coping with chronic 2015 Nov OBJECTIVE: Chronic disease is a critical life event which demands significant psychological adjustment. Coping strategies and resources such as sense of coherence, self-efficacy, etc. remain factors affecting stress response. PATIENTS AND METHODS: The examined group included patients with ischemic heart disease (n = 134), type 1 diabetes mellitus (n = 109) or rheumatoid arthritis (n = 92). 159 patients came from urban area whereas 176 came from rural setting. All patients filled up inventories of life satisfaction, severity of depression, coping strategies, self-efficacy, social support and sense of coherence. RESULTS: The analysis showed that patients from rural areas had higher levels of well-being, i.e., were characterized by lower severity of depression. The predictors of satisfaction with life included two types of resources i.e. self-efficacy, social support and two coping strategies i.e. turning to religion and self-distraction (R2 = 0.39; F = 26.87**). Life satisfaction was determined by social support, sense of coherence and positive reappraisal (R2 = 0.36; F = 29.11**). CONCLUSIONS: Rural/urban differences in the use of coping strategies may be associated with environmental or lifestyle differences. Patients with IHD, T1D or RA in Polish rural areas are high risk for depression so they may need help in finding systematic contact with specialists of healthcare.
26242859 Calprotectin more accurately discriminates the disease status of rheumatoid arthritis pati 2015 Dec OBJECTIVE: To compare the accuracy of serum calprotectin levels, CRP and ESR in stratifying disease activity in RA patients receiving tocilizumab (TCZ). METHODS: Cross-sectional study of 33 RA patients receiving TCZ. DAS28, Simplified Disease Activity Index, Clinical Disease Activity Index, joint counts and serum levels of CRP, ESR, calprotectin and TCZ were measured. Associations between calprotectin, ESR and CRP and articular indices were analysed by correlation and linear regression. The accuracy and discriminatory capacity of calprotectin was assessed by receiver operating characteristic curves (area under the curve). RESULTS: Calprotectin levels, but not CRP or ESR, were strongly correlated with all composite indices (all r coefficients over 0.50). Calprotectin, but not CRP or ESR, was significantly lower in patients in remission compared with those with low disease activity [1.57 μg/ml (s.d. 1) vs 3.35 μg/ml (s.d. 1), P = 0.001]. In a fully adjusted model (R(2) = 0.82), DAS28-ESR increased 0.48 units per μg/ml calprotectin increase (P < 0.001). Using a DAS28 >3.2 as the reference variable, calprotectin showed an area under the curve of 0.922, and the best cut-off was 5.19 μg/ml (odds ratio 11.5). CRP levels, but not calprotectin, were dependent on detectable TCZ trough serum levels. CONCLUSION: Calprotectin serum levels seem to be an accurate biomarker for assessing disease activity in RA patients receiving TCZ.
26302059 Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats. 2015 Oct 15 Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments usually cause severe gastrointestinal, renal and other complications. We aimed to evaluate the beneficial anti-arthritic effects of an angiotensin converting enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving ramipril (0.9 mg/kg/day) and haloperidol (1 mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid biomarkers, serum immunoglobulin G and antinuclear antibody as immunological biomarkers, serum tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced (GSH) as oxidative stress biomarkers were assessed. A histopathological study on joints and spleens was performed to support the results of biochemical estimations. Ramipril administration significantly corrected all the measured biomarkers, being restored back to normal levels except for MMP-3, TNF-α and IL-10. Haloperidol administration restored all the measured biomarkers back to normal levels except for TNF-α, IL-10 and GSH. In conclusion, ACE inhibitors represented by ramipril and dopamine receptor blockers represented by haloperidol may represent new promising protective strategies against RA, at least owing to their immunomodulatory, anti-inflammatory and antioxidant potentials.
25626592 A panoramic spectrum of complex interplay between the immune system and IL-32 during patho 2015 Jan 28 Cytokines have always been of great interest due to their vast potential and participation in the progression and pathogenesis of various ailments. Interleukin-32 (IL-32) is a recently identified cytokine, whose gene is located on human chromosome 16 p13.3, with eight exons and six splice variants (IL-32α to IL-32ζ). IL-32α, the most abundant form, is secreted by different types of cells including T cells, natural killer (NK) cells, monocytes, endothelial cells and epithelial cells. It acts as a preferential mediator and effector of abnormal immune responses to multiple inflammatory and auto immune diseases including rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), etc. It was found to stimulate the induction of various chemokines, pro-inflammatory cytokines including IL-1β, IL-6, IL-8, TNF-α and macrophage inflammatory protein-2 (MIP-2). Hence, IL-32 mediates the crucial interplay among immune system and body cells during pathogenesis of various insults. The aim of the present effort is to summarize the role, mechanism of pathogenesis and potential therapeutic applications of IL-32 in different systemic infections and diseased conditions.
26428204 Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When 2015 Nov OBJECTIVE: To evaluate the risk of having a disease flare in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD) therapy. METHODS: A search in medical databases including publications from January 1950 to February 2015 was performed. Included were trials and observational studies in adults with RA who were in LDA or remission, evaluating ≥ 20 patients tapering or stopping DMARD. Flare rates had to have been reported. A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF) blockers. RESULTS: Four studies evaluated synthetic DMARD. Flare rates ranged from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies reported on TNF blockers. Estimated flare rates by metaanalysis on studies tapering or stopping TNF blockers were 0.26 (95% CI 0.17-0.39) and 0.49 (95% CI 0.27-0.73) for good-quality and moderate-quality studies, respectively. Flare rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year, and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1 year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic progression in patients deescalating treatment all found limited to no progression. CONCLUSION: Results suggest that more than one-third of patients with RA with LDA or in remission may taper or stop DMARD treatment without experiencing a disease flare within the first year. Dose reduction of TNF blockers results in lower flare rates than stopping and may be noninferior to continuing full dose. Radiological progression after treatment deescalation remains low, but may increase slightly.
25999184 Impact of Switching From an Initial Tumor Necrosis Factor Inhibitor on Health Care Resourc 2015 Jul 1 PURPOSE: Despite improved clinical outcomes for the majority of patients, nearly 30% of patients with rheumatoid arthritis (RA) who initiate tumor necrosis factor antagonist (anti-TNF) biologic agents fail to respond to their first-line anti-TNF and switch to another anti-TNF or a non-TNF biologic. How this change affects health care costs and resource utilization is unknown. We therefore compared RA patients taking first-line anti-TNFs who switched to a second anti-TNF versus those patients who switched to an alternate biologic. METHODS: Health care claims data were obtained from a large US database for eligible adults with confirmed RA diagnoses who initiated anti-TNF treatment and switched to another biologic. Health care costs and utilization during the first 12 months' postswitch were compared. Generalized linear models were used to adjust for differences in demographic and clinical characteristics before switching. FINDINGS: Patients who switched to a second anti-TNF rather than a non-TNF biologic were generally younger (53.0 vs. 55.3 years; P < 0.0001) and less likely to be female (79.7% vs. 82.7%; P = 0.0490). Of the 3497 eligible patients who switched from first-line anti-TNFs, 2563 (73.3%) switched to another anti-TNF and 934 (26.7%) switched to a non-TNF. Adalimumab was the most frequently prescribed (43.4%) second-line anti-TNF, and abatacept was the most common non-anti-TNF (71.4%). Patients who switched to a second anti-TNF remained on their first medication for a significantly shorter period (342.5 vs 420.6 days; P < 0.0001) and had lower comorbidity indices and higher disease severity at baseline than those who switched to a non-anti-TNF. After adjusting for baseline differences, patients who switched to second anti-TNFs versus a non-TNF incurred lower RA-related costs ($20,938.9 vs $22,645.2; P = 0.0010) and total health care costs ($34,894.6 vs $38,437.2; P = 0.0010) 1 year postswitch. These differences were driven by increased physician office visit costs among the non-TNF group. IMPLICATIONS: Among the anti-TNF initiators who switched therapy, more patients switched to a second anti-TNF than to a non-TNF. Switching to a second anti-TNF treatment was associated with lower all-cause and RA-related health care costs and resource utilization than switching to a non-TNF. Because switching therapy may be unavoidable, finding a treatment algorithm mitigating this increase to any extent should be considered. These data are limited by their retrospective design. Additional confounding variables that could not be controlled for may affect results.
27832792 Gout: will the "King of Diseases" be the first rheumatic disease to be cured? 2016 Nov 11 Gout is the most common inflammatory arthritis in adults in the Western world. Characterized by hyperuricemia and the effects of acute and chronic inflammation in joints and bursa, gout leads to an agonizing, chronically painful arthritis. Arthritis can also be accompanied by urate nephropathy and subcutaneous urate deposits (tophi). Exciting new developments in the last decade have brought back the focus on this interesting, crystal-induced chronic inflammatory condition. New insights include the role of NALP3 inflammasome-induced inflammation in acute gout, the characterization of diagnostic signs on ultrasound and dual-energy computed tomography imaging modalities, the recognition of target serum urate less than 6 mg/day as the goal for urate-lowering therapies, and evidence-based treatment guidelines. A better understanding of disease mechanisms has enabled drug discovery - three new urate-lowering drugs have been approved in the last decade, with several more in the pipeline. We now recognize the important role that environment and genetics play in the causation of gout. A focus on the cardiac, renal, and metabolic comorbidities of gout will help translational research and discovery over the next decade.
25410437 Rheumatoid arthritis patients with hip fracture: a nationwide study. 2015 Feb SUMMARY: The study was to investigate the outcomes of rheumatoid arthritis (RA) patients with hip fractures with a large-scale, population-based, nationwide, case-cohort study using the Taiwan National Health Insurance database. The group has hip fractures at a younger age, higher complication, and mortality rate, which indicate that early intervention is necessary. INTRODUCTION: This study seeks to evaluate the incidence, mortality, and complication rates in RA patients with hip fractures, using a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 117,129 patients with hip fractures diagnosed from January 2004 to December 2010. Matching based on the propensity of RA patients was used. In total, 1,088 hip fractures were reported among patients with RA. Patients with hip fractures were divided into two groups: those without RA (controls) and those with RA (RA group). The incidence of hip fracture and mortality and complication rates after the hip fracture were then compared between the two groups. RESULTS: RA patients had a significantly higher incidence of hip fracture (3,260/100,000 person-years) compared with the general population (72/100,000 person-years). Hip fractures occurred significantly earlier among RA patients (70.6±5.3 years) compared with the control group (76.1±6.2 years). Cumulative mortality rates at 6-month and 1-year follow-up were significantly higher among patients in the RA group (9.47 and 18.47%) compared to the controls (8.47 and 13.62%) and among RA patients without hip fractures (3.24 and 6.16%). There was a significantly higher incidence of osteomyelitis after hip fracture among the RA group than among the body mass index-, comorbidity-, age-, and sex-matched patients in the control group. CONCLUSIONS: Compared to patients without RA, those with RA have a higher incidence of hip fractures at a relatively younger age and with higher complication and mortality rates. Steroid and disease-modifying anti-rheumatic drugs, the most common medicine in Taiwanese RA patients, might contribute to the high incidence of fracture and post-op infection. Appropriate early intervention to prevent hip fractures in RA patients is a critical issue in rheumatology care.
27054952 Hyaluronan Inhibits Tlr-4-Dependent RANKL Expression in Human Rheumatoid Arthritis Synovia 2016 The Toll-like receptor (TLR) signaling pathway is activated in synovial fibroblast cells in patients with rheumatoid arthritis (RA). The receptor activator of nuclear factor-κB (RANK) and its ligand, RANKL, are key molecules involved in the differentiation of osteoclasts and joint destruction in RA. Hyaluronan (HA) is a major extracellular component and an important immune regulator. In this study, we show that lipopolysaccharide (LPS) stimulation significantly increases RANKL expression via a TLR-4 signaling pathway. We also demonstrate that HA suppresses LPS-induced RANKL expression, which is dependent on CD44, but not intercellular adhesion molecule-1 (ICAM-1). Our study provides evidence for HA-mediated suppression of TLR-4-dependent RANKL expression. This could present an alternative target for the treatment of destructed joint bones and cartilages in RA.
27111223 Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affec 2016 OBJECTIVES: To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA). METHODS: In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined. RESULTS: After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs. CONCLUSION: The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA.
25819273 Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells deriv 2015 May 1 The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice.
26084468 Validation of a flow cytometry-based assay to assess C5aR receptor occupancy on neutrophil 2016 Mar The C5a/C5a receptor (C5aR) pathway, a key component in the proinflammatory immune response, is an attractive therapeutic target since its dysregulation is implicated in a variety of autoimmune and inflammatory disorders. The objective of the present study was to validate a receptor occupancy (RO) assay for a human anti-C5aR monoclonal antibody drug candidate, NNC0215-0384 (NN0384). This flow cytometry-based assay measures the percentage (%), median fluorescence intensity (MFI), and molecules of equivalent soluble fluorochrome (MESF) of NN0384 binding to its target cells, neutrophils and monocytes, in whole blood from normal healthy donors and rheumatoid arthritis (RA) patients with clinically active disease. The validation parameters assessed included postcollection and postprocessing sample stability, intra- and interassay precision, an analyst-to-analyst comparison, a comparison of normal healthy donor and RA patient sample postcollection stability, and a laboratory-to-laboratory comparison and assay transfer. The cumulative results indicate that the assay was reproducible, met the clearly defined acceptance criteria for the validation parameters tested, and was transferable to another laboratory. In conclusion, this RO assay is suitable for use to accrue pharmacodynamic biomarker data in a multicenter, global clinical trial.
26984007 Response to biological treatment and subsequent risk of coronary events in rheumatoid arth 2016 Dec OBJECTIVES: Whether the increased risk of comorbidities, such as cardiovascular disease, in rheumatoid arthritis (RA) can be reverted by particular antirheumatic therapies, or response to these, is unclear but of critical clinical importance. We wanted to investigate whether response to tumour necrosis factor inhibitors (TNFi) translates into a reduced risk for acute coronary syndrome (ACS). METHODS: A cohort of patients with RA initiating a first TNFi 2001-2012 was identified in the Swedish Biologics Register. The association between European League Against Rheumatism (EULAR) response after 3-8 months of treatment (assessed using the first, the best and the measurement closest to 5 months, respectively), and the risk of incident ACS during the subsequent year was analysed in Cox regression models. Adjustments included cardiovascular risk factors, joint surgery, RA duration, education and work disability. RESULTS: During 6592 person-years among TNFi initiators (n=6864, mean age 55 years, 77% women), 47 ACS occurred. The adjusted HRs (95% CI), which were similar to the crude HRs, of the 1-year risk of ACS among EULAR good responders compared with non-responders were 0.5 (0.2 to 1.4), 0.4 (0.2 to 0.9) and 0.5 (0.2 to 1.2), for the first, the best and the evaluation closest to 5 months, respectively. EULAR moderate responders had equal risk to that of EULAR non-responders, who, compared with the general population referents (n=34 229), had a more than twice the risk of ACS. For good responders, there was no statistically significant difference in risk versus the general population. CONCLUSIONS: Optimised RA disease control has the potential to revert otherwise increased risks for ACS in RA.
26892812 Prevalence and Factors Associated with Subclinical Left Ventricular Systolic Dysfunction E 2016 Sep OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased cardiovascular event rate, mainly due to the arterial stiffness which leads to coronary atherosclerosis and concentric left ventricular (LV) geometry. These conditions predispose to LV systolic dysfunction (LVSD), which can be detected by stress-corrected mid-wall shortening (sc-MS), an early prognosticator of cardiovascular events in asymptomatic patients with arterial hypertension and/or diabetes. In these subjects, sc-MS is frequently impaired even though LV ejection fraction (LVEF) is preserved. In this study, we analyzed the prevalence and the factors associated with asymptomatic LVSD measured by sc-MS among patients with RA and verified whether RA per se was independently related to LVSD. METHODS: We prospectively recruited 198 outpatients with RA without overt cardiac disease between January and June 2014 and compared them to 198 controls matched for age, gender, body mass index, and prevalence of hypertension and diabetes. sc-MS was taken as index of LVSD and considered impaired if <86.5%. RESULTS: Impaired sc-MS was detected in 110 (56%) RA patients and in 30 (15%) controls (P < 0.001), whereas LVEF was impaired (value <50%) in six (3%) RA patients and in two (1%) controls (P = ns). Multiple logistic regression analysis revealed that RA was independently associated with impaired sc-MS (Exp β 2.01 [CI 1.12-3.80], P = 0.02) together with increased LV mass and concentric geometry. CONCLUSIONS: More than half RA patients without overt cardiac disease have LVSD detectable by sc-MS. RA emerges as a condition closely related to LVSD. These findings might explain the high risk for adverse cardiovascular events in RA patients.
27515300 Factors predicting pain and early discontinuation of tumour necrosis factor-α-inhibitors 2016 Aug 12 BACKGROUND: We examined pain levels in 2 cohorts assembled from the British Society for Rheumatology Biologics Register (BSRBR), and investigated which factors predicted Bodily Pain scores and discontinuation of TNFα-inhibitors. METHOD: Data were retrieved from BSRBR-RA databases for up to 1 year after commencing TNFα-inhibitors (n = 11995) or being treated with non-biologic therapies (n = 3632). Bodily Pain scores were derived from the Short Form-36 (SF36) questionnaire and norm-transformed to allow comparison with UK population averages. Discontinuation data were from physician reports. Other data, including 28-joint disease activity score (DAS28) measurements, were from clinical examination, interview, medical records and self-report questionnaires. DAS28-P was derived as the proportion of DAS28 attributed to patient-reported factors (tender joint count and visual analogue score). Missing baseline variables from both cohorts were imputed into 20 replicate datasets. Odds ratios (OR) and adjusted OR were calculated for higher than median pain within each cohort. RESULTS: Participants reported moderate to severe pain at baseline, and pain scores remained >1SD worse than normal population standards at 1 year, even when disease activity responded to treatment. Baseline pain was associated with DAS28-P, worse physical function, worse mental health, and DAS28. After logistic regression, independent predictors of higher than median pain at follow up were baseline Bodily Pain score, higher DAS28-P, worse physical function or mental health and co-morbidities. Higher age, male gender, and higher BMI were additional independent predictors of higher pain in participants who received TNFα-inhibitors. Baseline pain was also one of the predictors of discontinuation of the first TNFα-inhibitor within 1 year, as were female gender, current smoking, co-morbidities, extra-articular manifestations and worse function. CONCLUSION: Pain persists in people with treated RA, even in those for whom inflammation responds to treatment. Worse pain outcomes are predicted by factors different to those typically found to predict inflammatory disease activity in other studies. Worse pain at baseline also predicts discontinuation of TNFα-inhibitors. Improved pain management should complement inflammatory disease suppression in RA.
28116320 The Mechanisms Underlying Chronic Inflammation in Rheumatoid Arthritis from the Perspectiv 2016 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is characterized by synovial hyperplasia and progressive joint destruction. The activation of RA synovial fibroblasts (SFs), also called fibroblast-like synoviocytes (FLS), contributes significantly to perpetuation of the disease. Genetic and environmental factors have been reported to be involved in the etiology of RA but are insufficient to explain it. In recent years, accumulating results have shown the potential role of epigenetic mechanisms, including histone modifications, DNA methylation, and microRNAs, in the development of RA. Epigenetic mechanisms regulate chromatin state and gene transcription without any change in DNA sequence, resulting in the alteration of phenotypes in several cell types, especially RASFs. Epigenetic changes possibly provide RASFs with an activated phenotype. In this paper, we review the roles of epigenetic mechanisms relevant for the progression of RA.
28042124 Improvement in Herpes Zoster Vaccination in Patients with Rheumatoid Arthritis: A Quality 2017 Jan OBJECTIVE: To improve herpes zoster (HZ) vaccination rates in high-risk patients with rheumatoid arthritis (RA) being treated with immunosuppressive therapy. METHODS: This quality improvement project was based on the pre- and post-intervention design. The project targeted all patients with RA over the age of 60 years while being treated with immunosuppressive therapy (not with biologics) seen in 13 rheumatology outpatient clinics. The study period was from July 2012 to June 2013 for the pre-intervention and February 2014 to January 2015 for the post-intervention phase. The electronic best practice alert (BPA) for HZ vaccination was developed; it appeared on electronic medical records during registration and medication reconciliation of the eligible patient by the medical assistant. The BPA was designed to electronically identify patient eligibility and to enable the physician to order the vaccine or to document refusal or deferral reason. Education regarding vaccine guidelines, BPA, vaccination process, and feedback were crucial components of the project interventions. The vaccination rates were compared using the chi-square test. RESULTS: We evaluated 1823 and 1554 eligible patients with RA during the pre-intervention and post-intervention phases, respectively. The HZ vaccination rates, reported as patients vaccinated among all eligible patients, improved significantly from the pre-intervention period of 10.1% (184/1823) to 51.7% (804/1554) during the intervention phase (p < 0.0001). The documentation rates (vaccine received, vaccine ordered, patient refusal, and deferral reasons) increased from 28% (510/1823) to 72.9% (1133/1554; p < 0.0001). The HZ infection rates decreased significantly from 2% to 0.3% (p = 0.002). CONCLUSION: Electronic identification of vaccine eligibility and BPA significantly improved HZ vaccination rates. The process required minimal modification of clinic work flow and did not burden the physician's time, and has the potential for self-sustainability and generalizability.
26852086 Calcium channels: the potential therapeutic targets for inflammatory bone destruction of r 2016 May INTRODUCTION: Inflammatory bone resorption causes progressive joint destruction which ultimately leads to functional disability in rheumatoid arthritis (RA). The primary cell responsible for bone resorption is the osteoclast, which means it is a potential therapeutic target against bone destruction. In fact, experimental and clinical findings suggest that blockade of osteoclast differentiation and function is highly effective in inhibiting bone destruction in RA. DISCUSSION AND CONCLUSION: In this report, we show several lines of experimental evidence which suggest that a variety of Ca(2+) channels are essential in osteoclast differentiation and function, and present a hypothesis that modulation of Ca(2+) channels is a highly effective therapeutic strategy in preventing osteoclast-induced structural damage in RA.