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ID PMID Title PublicationDate abstract
25228045 Safety of glucocorticoids in rheumatoid arthritis: evidence from recent clinical trials. 2015 Glucocorticoids are one of the most effective treatments for rheumatoid arthritis, with well-established efficacy in controlling the disease symptoms and structural progression. Fears regarding their toxicity are reflected in common recommendations for the use of the lowest possible dose for the shortest possible time. We herein review toxicity data obtained in randomized clinical trials of low-dose glucocorticoid in rheumatoid arthritis, given that observational studies cannot guarantee the avoidance of bias by indication. Seven eligible randomized controlled trials were identified. These publications do not identify any strong signal of relevant toxicity of glucocorticoid in doses of up to 10 mg of prednisone equivalent/day for up to 2 years. However, the quantity (1,100 patient years of exposure) and especially the quality of evidence are too limited to establish conclusions. A large prospective trial dedicated to the toxicity of low-dose glucocorticoid is dearly needed. Meanwhile, adherence to recommendations on standardized methodologies for the registration and report of glucocorticoid adverse events is essential to improve our knowledge and competence in the best management of these important medications.
23528639 Cervical spine manifestations in patients with inflammatory arthritides. 2013 Jul The cervical spine can frequently become involved in patients with rheumatologic disorders, as a result of either the rheumatologic disease itself or age-associated degenerative processes that can also occur in the rest of the population. Awareness of the increased risk of cervical spine manifestations in patients with rheumatologic disorders enables early recognition and initiation of the appropriate treatment regimen. For example, patients with rheumatoid arthritis (RA) often have spinal instability which, if left untreated, can lead to neurological deficits. Biologic agents are effective in slowing the progression of the skeletal abnormality as well as for treating the RA, and this approach is often sufficient. However, early surgical intervention is recommended for patients with RA who develop neurologic deficits, as conservative approaches have limited effectiveness in this group. Spinal stability should be the primary surgical objective. For patients with ankylosing spondylitis, cervical spine surgery might be required either for fracture repair or to correct severe kyphosis. Understanding each condition's specific cervical spine manifestation and its natural history can help to clarify the appropriate indications for and timing of surgery to maximize patients' outcomes and limit complications.
24252896 Work ability and work disability evaluation in Saudi patients with rheumatoid arthritis. S 2013 Nov OBJECTIVE: To assess work ability and work satisfaction in Saudi Arabian patients with rheumatoid arthritis (RA) and to compare work ability outcomes and work satisfaction levels between housewives and paid workers both suffering from RA. METHODS: This is a cross sectional study on 120 patients with RA conducted at 3 hospitals between September 2011 and May 2012. The Quantity-Quality Method (Q-Q Method) and the Work Satisfaction Questionnaire were used for the assessment of the impact of RA on the work ability of the patients enrolled in this study. The RA disease severity was assessed using Disease Activity Score-28 (DAS-28) and Health Assessment Questionnaire (HAQ). RESULTS: The mean +/- standard deviation scores were: 5.45 +/- 2.533 (work quantity); 6.22 +/- 2.5218 (work quality); and 6.26 +/- 2.963 (work satisfaction). Work productivity lost due to RA was estimated to be 3.64 hours. Compared with paid workers included in the study, housewives had significantly lower work quantity (p=0.041), quality (p=0.021), and work satisfaction (p=0.040) scores. Fatigue, swollen joint count, tender joint count, HAQ, and the use of biologic therapy were found to be the variables that were significantly related to work quantity. CONCLUSION: Housewives with RA suffer worse work ability outcomes and poorer work satisfaction compared to paid workers with RA.
25374443 A natural flavonoid glucoside, icariin, regulates Th17 and alleviates rheumatoid arthritis 2014 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that causes deformity of the joints and physical disability. Icariin, a natural flavonoid glucoside isolated from plants in the Epimedium family, has been proven to have various pharmacological activities. A recent study showed that icariin suppressed cartilage and bone degradation in mice of collagen-induced arthritis. However, the mechanism needs to be further investigated. In our current study, we found that icariin reduced the arthritis score and the incidence of arthritis compared with that in mice treated with water. Icariin inhibits the expression of various osteoclastogenic markers, such as β3 integrin, cathepsin K, and MMP9 in vitro. Icariin treatment in mice with CIA also resulted in less number of Th17 cells and decreased ratio of CD4(+)IL-17(+) cells. The alleviated arthritis score and incidence of arthritis and reduced serum levels of IgG2a induced by icariin were abolished with additional IL-17 administration. Furthermore, icariin inhibited STAT3 activation in T cells and STAT3 inhibitor resulted in decreased IL-17 production and alleviated RA. In conclusion, icariin decreases Th17 cells and suppresses the production of IL-17, which contributes to the alleviated rheumatoid arthritis, through the inhibition of STAT3 activation.
24515434 Increased TTS expression in patients with rheumatoid arthritis. 2015 Feb Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The aim of this work was to study the imbalance expressions of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (TTS) with RA patients. Forty-nine RA patients and 49 healthy controls were studied. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry in peripheral blood mononuclear cells. The expression of TTS mRNA increased significantly in RA patients when compared with healthy controls and correlated with erythrocyte sedimentation rate (r = 0.424, P < 0.01). In addition, we found TTS increased significantly mainly in CD3(+) T cells in rheumatoid arthritis group. Increased TTS expressions from CD3(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in RA patients. Determination of expressions of TTS may provide a better understanding of progression of the disease.
23701120 Identification of a specific haptoglobin C-terminal fragment in arthritic synovial fluid a 2013 Sep Haptoglobin (Hp), a major acute-phase plasma protein, has been found in arthritic synovial fluid (SF). However, the function and structural modifications of Hp in arthritic SF are unknown. To investigate in vivo generation of modified Hp associated with inflammatory disease, we examined a new Hp isoform in SF from patients with rheumatoid arthritis (RA). Specific Hp fragments of 28 000 and 15 000 molecular weight were identified in SF of patients with RA, and the two polypeptides were presumed to be fragments of the Hp β-chain (43 000 MW) produced by cleavage with plasmin. The 15 000 MW fragment, which is a C-terminal region of Hp, was observed at higher frequency and levels in RA than in osteoarthritis. Plasmin activity was also higher in SF of RA patients. A recombinant 15 000 MW Hp fragment up-regulated interlukin-6 expression in monocytic cells. These findings indicate that the C-terminal Hp fragment is generated by plasmin in local inflammatory environments and acts as an inflammatory mediator. They further suggest that a specific Hp fragment might be applied as a novel biomarker for the diagnosis and prognosis of inflammatory diseases such as RA.
23234647 Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. 2013 Sep 1 OBJECTIVES: Mavrilimumab, a human monoclonal antibody targeting the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, was evaluated in a phase 2 randomised, double-blind, placebo-controlled study to investigate efficacy and safety in subjects with rheumatoid arthritis (RA). METHODS: Subcutaneous mavrilimumab (10 mg, 30 mg, 50 mg, or 100 mg) or placebo was administered every other week for 12 weeks in subjects on stable background methotrexate therapy. The primary endpoint was the proportion of subjects achieving a ≥1.2 decrease from baseline in Disease Activity Score (DAS28-CRP) at week 12. RESULTS: 55.7% of mavrilimumab-treated subjects met the primary endpoint versus 34.7% placebo (p=0.003) at week 12; for the 10 mg, 30 mg, 50 mg, and 100 mg groups, responses were 41.0% (p=0.543), 61.0% (p=0.011), 53.8% (p=0.071), and 66.7% (p=0.001) respectively. Response rate differences from placebo were observed at week 2 and increased throughout the treatment period. The 100 mg dose demonstrated a significant effect versus placebo on DAS28-CRP<2.6 (23.1% vs 6.7%, p=0.016), all categories of the American College of Rheumatology (ACR) criteria (ACR20: 69.2% vs 40.0%, p=0.005; ACR50: 30.8% vs 12.0%, p=0.021; ACR70: 17.9% vs 4.0%, p=0.030), and the Health Assessment Questionnaire Disability Index (-0.48 vs -0.25, p=0.005). A biomarker-based disease activity score showed a dose-dependent decrease at week 12, indicating suppression of disease-related biological pathways. Adverse events were generally mild or moderate in intensity. No significant hypersensitivity reactions, serious or opportunistic infections, or changes in pulmonary parameters were observed. CONCLUSIONS: Mavrilimumab induced rapid clinically significant responses in RA subjects, suggesting that inhibiting the mononuclear phagocyte pathway may provide a novel therapeutic approach for RA.
23772083 BAFF and TACI gene expression are increased in patients with untreated very early rheumato 2013 Aug OBJECTIVE: B cells play important roles in rheumatoid arthritis (RA). Given the beneficial effect of B cell depletion therapy in RA as well as the observed alterations in B cell subpopulations in this disease, we evaluated whether changes in the expression of genes related to B cell survival and activation were already present in patients with untreated very early RA (VERA; < 6 weeks of disease duration). METHODS: The expression of a group of B cell-related activation and survival genes was quantified in peripheral blood mononuclear cells from patients with VERA by real-time PCR and compared with untreated early RA (< 1 year), established treated RA, and other untreated early arthritis conditions. Serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) was quantified by ELISA. RESULTS: BAFF gene expression and serum levels were highest in patients with VERA. The expression of BAFF receptor (BAFF-R) increased with disease progression, while transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) was elevated since the first weeks of RA onset. Paired box 5 gene expression was also increased at all RA stages. Chemokine (C-X-C motif) receptor 5 was elevated only in established RA. No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression. CONCLUSION: Disturbances in the expression of B cell-related activation and survival genes, particularly BAFF and TACI, occur from the onset of RA and precede changes in BAFF-R. These alterations can lead to the development of autoreactive B cells from the first weeks of RA onset.
23661491 The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis. 2013 Aug OBJECTIVES: Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. Recent work has shown that systemic autoimmunity precedes synovial inflammation, and animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. Therefore, we investigated the cellular composition of the lymph node in the earliest phases of inflammatory arthritis. METHODS: Thirteen individuals positive for immunoglobulin M (IgM) rheumatoid factor and/or anticitrullinated protein antibodies without arthritis were included. Additionally, we studied 14 early arthritis patients (arthritis duration ≤6 months, naïve for disease-modifying antirheumatic drugs), and eight healthy controls. All subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T- and B-lymphocyte subsets were analysed by multicolour flow cytometry. RESULTS: There was an increase in activated CD69 CD8 T cells and CD19 B cells in early arthritis patients compared with healthy controls. We also observed a trend towards increased CD19 B cells in autoantibody-positive individuals without arthritis compared with healthy controls. CONCLUSIONS: This exploratory study suggests that there is increased immune cell activation within lymph nodes of early arthritis patients as well as in autoantibody-positive individuals at risk of developing RA. This method provides a unique tool to investigate immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis.
23370082 Impact of iyengar yoga on quality of life in young women with rheumatoid arthritis. 2013 Nov OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, disabling disease that can greatly compromise health-related quality of life (HRQoL). The aim of this study was to assess the impact of a 6-week twice/week Iyengar yoga program on HRQoL of young adults with RA compared with a usual-care waitlist control group. METHODS: The program was designed to improve the primary outcome of HRQoL including pain and disability and psychological functioning in patients. Assessments were collected pretreatment, posttreatment, and at 2 months after treatment. Weekly ratings of anxiety, depression, pain, and sleep were also recorded. A total of 26 participants completed the intervention (yoga=11; usual-care waitlist=15). All participants were female (mean age=28 y). RESULTS: Overall attrition was low at 15%. On average, women in the yoga group attended 96% of the yoga classes. No adverse events were reported. Relative to the usual-care waitlist, women assigned to the yoga program showed significantly greater improvement on standardized measures of HRQoL, pain disability, general health, mood, fatigue, acceptance of chronic pain, and self-efficacy regarding pain at posttreatment. Almost half of the yoga group reported clinically meaningful symptom improvement. Analysis of the uncontrolled effects and maintenance of treatment effects showed improvements in HRQoL general health, pain disability, and weekly ratings of pain, anxiety, and depression were maintained at follow-up. CONCLUSIONS: The findings suggest that a brief Iyengar yoga intervention is a feasible and safe adjunctive treatment for young people with RA, leading to HRQoL, pain disability, fatigue, and mood benefits. Moreover, improvements in quality of life, pain disability, and mood persisted at the 2-month follow-up.
24986850 Has the severity of rheumatoid arthritis at presentation diminished over time? 2014 Aug OBJECTIVE: To examine the pattern of disease severity in patients with rheumatoid arthritis (RA) at presentation to the Norfolk Arthritis Register (NOAR) over 20 years. METHODS: NOAR is a primary-care-based cohort of patients with recent-onset inflammatory polyarthritis. At baseline, subjects are assessed and examined by a research nurse. The Health Assessment Questionnaire (HAQ) is administered and the DAS28 (28-joint Disease Activity Score) is calculated. Information is collected on disease-modifying antirheumatic drug exposure. In this study, patients (symptom duration of < 2 years at baseline) were grouped into 4 cohorts (Cohort 1: 1990-1994; Cohort 2: 1995-1999; Cohort 3: 2000-2004; Cohort 4: 2005-2008). The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for RA were applied retrospectively at baseline. Regression analyses were used to examine whether calendar year of presentation to NOAR was associated with baseline HAQ and DAS28 scores. Potential confounders included age at symptom onset, sex, rheumatoid factor, and anticyclic citrullinated peptide antibody positivity. RESULTS: A total of 1724 patients met the ACR/EULAR 2010 RA criteria at baseline. Unadjusted mean DAS28 scores decreased over time. Calendar year of presentation to NOAR was significantly associated with lower DAS28 scores over time [Y = 4.51 + (-0.56 × year) + (0.44 × year(2))]. Although unadjusted median HAQ scores increased over time, calendar year of presentation to NOAR was not significantly associated with HAQ scores [Y = (1.1) + (0.023 × year) + (0.05 × year(2))]. Similar results were observed in each subpopulation of patients. CONCLUSION: While baseline disease activity has lessened slightly over time, there has been no improvement in baseline levels of functional disability.
24001888 Radiographic benefit and maintenance of clinical benefit with intravenous golimumab therap 2014 Dec OBJECTIVE: Report on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA). METHODS: Patients (n=592) with active RA (≥6/66 swollen, ≥6/68 tender joints, C reactive protein (CRP) ≥1.0 mg/dL and positive for rheumatoid factor and/or anticyclic citrullinated protein antibody at screening) despite MTX ≥3 months (stable dose of 15-25 mg/week for ≥4 weeks) participated in this multicentre, international, randomised, double blind, placebo controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg or placebo infusions at weeks 0 and 4 and then every 8 weeks; patients continued their stable MTX regimen. Placebo patients started golimumab 2 mg/kg at wk16 (early escape; <10% improvement in tender and swollen joints) or wk24 (crossover by design). Week 24 and wk52 radiographic (van der Heijde-Sharp (vdH-S) scores), clinical efficacy and safety data up to 1 year are reported here. RESULTS: Significant and rapid clinical improvement was observed up to wk24 of intravenous golimumab therapy. Golimumab+MTX treated patients demonstrated less radiographic progression than placebo treated patients at wk24 (vdH-S score mean change 0.03 vs 1.09; p<0.001) and wk52 (0.13 vs 1.22; p=0.001). Among patients with ≥20% improvement in the American College of Rheumatology response criteria or who achieved a 'good' or 'moderate' response according to the 28 joint Disease Activity Score employing CRP at wk24, approximately 80% maintained this response up until wk52. Through an average of 43.5 weeks of follow-up, 64.6% of patients receiving golimumab+MTX reported adverse events, most commonly non-serious infections. CONCLUSIONS: In patients with active RA despite MTX, intravenous golimumab+MTX yielded significant inhibition of structural damage at wk24 and wk52, and sustained clinical improvement in signs and symptoms with no new safety signals up to 1 year. CLINICALTRIALSGOV: NCT00973479, EudraCT 2008-006 064-11.
23232804 Analysis of critical molecules and signaling pathways in osteoarthritis and rheumatoid art 2013 Feb Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most prevalent forms of arthritis in the elderly. This study aimed to explore the molecular mechanisms of these diseases and identify underlying therapeutic targets. Using GSE1919 microarray data sets downloaded from the Gene Expression Omnibus database, we screened differentially expressed genes (DEGs) in OA and RA cells. The underlying molecular mechanisms of these crucial genes were investigated by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Small molecule expression and SNP analysis were also conducted by searching CMap and dbSNP databases. More than 320 genes changed in the arthritic cells and there were only 196 DEGs between OA and RA. OA and RA activated the classic mitogen-activated protein kinase signaling pathway, insulin signaling pathway, antigen processing and presentation and intestinal immune network for IgA production. Graft-versus-host disease and autoimmune thyroid disease-related pathways were also activated in OA and RA. Parthenolide and alsterpaullone may be treatments for OA and RA and insulin-like growth factor 1, collagen α2(I) chain and special AT-rich sequence-binding protein 2 may be critical SNP molecules in arthritis. Our findings shed new light on the common molecular mechanisms of OA and RA and may provide theoretical support for further clinical therapeutic studies.
25405351 Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. 2014 A subset of patients with autoimmune diseases including rheumatoid arthritis (RA) and lupus appear to be exposed continually to interferon (IFN) as evidenced by elevated expression of IFN induced genes in blood cells. In lupus, detection of endogenous chromatin complexes by the innate sensing machinery is the suspected driver for the IFN, but the actual mechanisms remain unknown in all of these diseases. We investigated in two randomized clinical trials the effects on RA patients of baminercept, a lymphotoxin-beta receptor-immunoglobulin fusion protein that blocks the lymphotoxin-αβ/LIGHT axis. Administration of baminercept led to a reduced RNA IFN signature in the blood of patients with elevated baseline signatures. Both RA and SLE patients with a high IFN signature were lymphopenic and lymphocyte counts increased following baminercept treatment of RA patients. These data demonstrate a coupling between the lymphotoxin-LIGHT system and IFN production in rheumatoid arthritis. IFN induced retention of lymphocytes within lymphoid tissues is a likely component of the lymphopenia observed in many autoimmune diseases. ClinicalTrials.gov NCT00664716.
23684320 Reproducible metacarpal joint space width measurements using 3D analysis of images acquire 2013 Oct OBJECTIVE: Joint space narrowing is an important feature of progressive joint damage and functional impairment in rheumatoid arthritis (RA). Methods to provide a continuous measurement of joint space width have not been adopted in research or clinical settings. High-resolution peripheral quantitative computed tomography (HR-pQCT) (Scanco Medical AG, Brüttisellen, Switzerland) accurately and reproducibly images bone microstructure at a nominal isotropic voxel dimension of 82 μm. Given the ability of HR-pQCT to detect bone margins with high precision, we developed methodology to measure a three-dimensional (3D) metacarpophalangeal (MCP) joint space width and tested the reproducibility of the scan protocol with hand repositioning. MATERIALS AND METHODS: Consecutive HR-pQCT scans of the 2nd and 3rd MCP joints of ten subjects with early RA (70% female, mean age 45 years), with repositioning between scans, were obtained. The periosteal edges of the metacarpal head and proximal phalanx base were detected using the μCT Evaluation Program V6.0 (Scanco Medical AG). Using the method of 'fitting maximal spheres', the joint space width and distribution of joint space thickness was estimated. RESULTS: The mean minimum joint space width of the 2nd MCP was 1.82 mm (SD 0.20) and of the 3rd MCP 1.84 mm (SD 0.23). Reproducibility with repositioning was reliable, with overlapping filtered histograms and a root square mean coefficient of variance of 4.8%. CONCLUSIONS: We provide reproducible methodology for evaluating the joint space width of the MCP joints. When combined with the assessment of erosions and periarticular bone density, HR-pQCT may be the ideal technology to assess disease activity and progression in RA.
25128520 When to adjust therapy in patients with rheumatoid arthritis after initiation of etanercep 2014 Oct OBJECTIVE: The objective of these posthoc analyses was to evaluate short-term clinical outcomes as predictors of poor response after 1 year of treatment with combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in patients with early rheumatoid arthritis (RA). METHODS: Participants with moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) ≥ 3.2] of 3-24 months' duration received ETN 50 mg weekly plus MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor clinical short-term treatment effects (e.g., absolute or changes from baseline in DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy). RESULTS: The magnitude of disease activity and its improvement and timing influenced remission probability in both treatment groups; remission rate was diminished with higher disease activity levels and lower response levels over time from weeks 4 to 24. The rate of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX alone at most timepoints from weeks 4 to 24. Despite persistent high disease activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%, 25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR remission after 1 year of continuous treatment; the respective proportions were 33%, 27%, 8%, and 13% in the MTX group. CONCLUSION: High disease activity and less improvement with treatment over time in the initial 24 weeks of treatment, particularly after 12 weeks, were predictive of a lower remission rate after 1 year.
22992002 The effect of anti-TNF-α vs. DMARDs on fatigue in rheumatoid arthritis patients. 2013 OBJECTIVES: Fatigue is experienced frequently by patients with rheumatoid arthritis (RA). Fatigue may be caused by high levels of pain and disease activity in RA but can remain present while disease activity is moderate to low. It is not clear whether RA patients receiving anti-tumour necrosis factor (TNF) treatment reach lower levels of acute fatigue than RA patients receiving disease-modifying anti-rheumatic drug (DMARD) treatment. The aim of our study was to analyse whether, in patients with RA, the effect of anti-TNF on fatigue is greater than the effect of DMARD treatment. METHOD: Sixty-seven RA patients receiving anti-TNF treatment and 104 RA patients receiving DMARDs were included. All patients were on stable treatment for at least 6 months prior to baseline measurement. Fatigue was measured monthly over 1 year with the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue). The association between persistent severe fatigue and medication group was analysed using multiple linear regression including confounders. RESULTS: In the anti-TNF group the mean (SD) level of persistent fatigue was significantly higher than in the DMARD group [32.2 (11.4) vs. 28.3 (10.9), p = 0.025] and more patients experienced persistent severe (CIS-fatigue score ≥ 35) fatigue (42% and 27% respectively, p = 0.043). However, when correcting for age, disease activity, haemoglobin, treatment duration, pain, physical disability, and clinical depression, medication type seemed to influence neither the mean level of persistent fatigue (p = 0.251) nor the percentage of patients with persistent severe fatigue (p = 0.745). CONCLUSIONS: When taking into account probable confounders including disease activity, medication type did not influence persistent fatigue in RA patients. It seems that, besides its anti-inflammatory effect, anti-TNF has no complementary effect on persistent fatigue.
22718576 Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory 2013 Feb BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker increasingly used for the assessment of systemic inflammation. We aimed to evaluate suPAR for the assessment of inflammatory activity in rheumatoid arthritis (RA) patients in remission. METHODS: In our cross-sectional study we measured plasma suPAR and C-reactive protein (CRP) levels as well as erythrocyte sedimentation rate (ESR) in 120 RA patients at various stages of disease activity and 29 healthy age-matched controls. RESULTS: suPAR, CRP and ESR values were higher in RA patients compared to healthy individuals. When suPAR levels were analyzed according to DAS28 scores of RA patients, suPAR level in the subgroup with DAS28≤2.6 was lower than in the subgroup with DAS28>2.6, but still higher than in controls [4.45 (3.33-5.56) ng/mL vs. 3.66 (3.10-4.67) ng/mL vs. 2.80 (2.06-3.42) ng/mL, p<0.0001, median (interquartile range)]. In contrast, CRP and ESR values were comparable in the subgroup with DAS28≤2.6 and in healthy individuals. We further analyzed the correlation between the number of tender and/or swollen joints and suPAR levels in RA patients in remission. suPAR values were significantly higher in patients with four tender and/or swollen joints than in patients with 2-3 or 0-1 tender and/or swollen joints. CONCLUSIONS: While CRP and ESR values indicate remission of the chronic inflammatory process in RA, suPAR values are still elevated compared to healthy individuals. suPAR might be particularly valuable in the recognition of inflammatory activity in patients who are in remission according to DAS28 scores but have symptoms of tender and/or swollen joints.
24314299 Serum level of adiponectin is a surrogate independent biomarker of radiographic disease pr 2013 INTRODUCTION: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA. METHODS: In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥ 5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion). RESULTS: Adiponectin level was independently associated with baseline total SHS (adjusted β = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 μg/ml for ∆SHS ≥1 and 6.04 μg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively). CONCLUSION: Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.
24462839 Incidence, prevalence, costs, and impact on disability of common conditions requiring reha 2014 May OBJECTIVE: To determine the relative incidence, prevalence, costs, and impact on disability of 8 common conditions treated by rehabilitation professionals. DATA SOURCES: Comprehensive bibliographic searches using MEDLINE, Google Scholar, and UpToDate, (June, 2013). DATA EXTRACTION: Two review authors independently screened the search results and performed data extraction. Eighty-two articles were identified that had relevant data on the following conditions: Stroke, Spinal Cord Injury, Traumatic Brain Injury, Multiple Sclerosis, Osteoarthritis, Rheumatoid Arthritis, Limb Loss, and Back Pain. DATA SYNTHESIS: Back pain and arthritis (osteoarthritis, rheumatoid arthritis) are the most common and costly conditions we analyzed, affecting more than 100 million individuals and costing greater than $200 billion per year. Traumatic brain injury, while less common than arthritis and back pain, carries enormous per capita direct and indirect costs, mostly because of the young age of those involved and the severe disability that it may cause. Finally, stroke, which is often listed as the most common cause of disability, is likely second to both arthritis and back pain in its impact on functional limitations. CONCLUSIONS: Of the common rehabilitation diagnoses we studied, musculoskeletal conditions such as back pain and arthritis likely have the most impact on the health care system because of their high prevalence and impact on disability.