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ID PMID Title PublicationDate abstract
27766911 The minimally important difference for the Japanese version of the health assessment quest 2017 May OBJECTIVE: To validate the minimally important difference (MID) of physical function using the Japanese version of the Health Assessment Questionnaire (J-HAQ) in a cohort of rheumatoid arthritis (RA). METHODS: Patients who participated in a cohort study in both October 2008 and April 2009 were analyzed. Patients self-rated their change in overall status over 6 months using a 5-point Likert scale ("much better", "somewhat better", "same", "somewhat worse", or "much worse"). The MID for J-HAQ score was defined as the mean J-HAQ score change in patients who rated themselves "somewhat better". An effect size (ES) of 0.2-0.5 was considered to be suitable for MID. RESULTS: A total of 4560 patients were analyzed. The mean (standard deviation [SD]) MID for J-HAQ score was -0.06 (0.29), corresponding to an ES of 0.08. As exploratory analysis, 1999 patients with a J-HAQ score ≥0.5 and 28-joint disease activity score (DAS28) ≥ 2.6 at baseline were assessed. The mean (SD) MID for J-HAQ score of these patients was 0.13 (0.01), corresponding to an ES of 0.21. CONCLUSIONS: The MID for J-HAQ score was 0.13 in patients with baseline J-HAQ score ≥0.5 and DAS28 ≥ 2.6. The MID for J-HAQ score was influenced by disease status and functional disability.
26279255 Antibodies to high-density lipoproteins are associated with inflammation and cardiovascula 2015 Dec Several lines of evidence suggest that chronic inflammation and immune dysregulation are related to altered lipid profiles in rheumatoid arthritis (RA), but the actual mechanisms are still unclear. We wondered whether the development of antibodies against high-density lipoprotein (HDL) can be found in RA patients linked to clinical and cardiovascular (CV) risk factors. To this end, immunoglobulin G (IgG) anti-HDL antibodies and total IgG serum levels were quantified in 212 RA patients, 131 sex- and age-matched healthy controls (HC), and 52 subjects with traditional CV risk factors (tCVRs). A subgroup of 13 RA patients was prospectively followed on TNFα-blockade. TNFα, interferon (IFN)α, MIP1α, IFNγ, IL-8, VEGF, GM-CSF, IL-17, MCP-1, SDF-1α, resistin, and leptin serum levels were quantified by immunoassays. IgG anti-HDL levels were higher in RA patients compared with HC (P < 0.0001) and tCVR subjects (P = 0.015). Differences with HC remained after correction for total IgG levels (P < 0.003). Anti-HDL/IgG were negatively associated with HDL levels in RA (-1.182 [-1.823 to -0.541], P = 0.0003) after adjusting for demographical, clinical, inflammatory parameters, and treatments. RA patients with high levels of anti-HDL/IgG (n = 40, 18.8%) were more likely to have experienced a CV event (P < 0.0001) and exhibited increased levels of several proinflammatory mediators (C-reactive protein, IFNα, MIP1α, IFNγ, IL-8, GM-CSF, IL-17 and MCP-1). Finally, change in anti-HDL antibodies on TNFα-blockade was independently associated with increasing HDL levels. Overall, IgG anti-HDL antibodies are increased in RA independently of tCVRs and associated with a proinflammatory milieu and impaired lipid blood profile, which may contribute to the increased rate of CV events in these patients.
25967362 Mechanical loading reduces inflammation-induced human osteocyte-to-osteoclast communicatio 2015 Aug Multiple factors contribute to bone loss in inflammatory diseases such as rheumatoid arthritis (RA), but circulating inflammatory factors and immobilization play a crucial role. Mechanical loading prevents bone loss in the general population, but the effects of mechanical loading in patients with RA are less clear. Therefore, we aimed to investigate whether mechanical stimuli reverse the stimulatory effect of RA serum on osteocyte-to-osteoclast communication. Human primary osteocytes were pretreated with 10 % RA serum or healthy control serum for 7 days, followed by 1 h ± mechanical loading by pulsating fluid flow (PFF). Nitric oxide (NO) and prostaglandin E2 were measured in the medium. Receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), cyclooxygenase-2 (COX2), matrix-extracellular phosphoglycoprotein (MEPE), cysteine-rich protein 61 (CYR61), and SOST gene expression was quantified by qPCR. Osteoclast precursors were cultured with PFF-conditioned medium (PFF-CM) or static-conditioned medium (stat-CM), and osteoclast formation was assessed. RA serum alone did not affect IL-6, CYR61, COX2, MEPE, or SOST gene expression in osteocytes. However, RA serum enhanced the RANKL/OPG expression ratio by 3.4-fold, while PFF nullified this effect. PFF enhanced NO production to the same extent in control serum (2.6-3.5-fold) and RA serum-pretreated (2.7-3.6-fold) osteocytes. Stat-CM from RA serum-pretreated osteocytes enhanced osteoclastogenesis compared with stat-CM from control serum-pretreated osteocytes, while PFF nullified this effect. In conclusion, RA serum, containing inflammatory factors, did not alter the intrinsic capacity of osteocytes to sense mechanical stimuli, but upregulated osteocyte-to-osteoclast communication. Mechanical loading nullified this upregulation, suggesting that mechanical stimuli could contribute to the prevention of osteoporosis in inflammatory disease.
27123622 An Evaluation of Rituximab for Rheumatoid Arthritis. 2016 May Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library.
27084907 Interleukin 34 Upregulation Contributes to the Increment of MicroRNA 21 Expression through 2016 Jul OBJECTIVE: Interleukin 34 (IL-34) and microRNA 21 (miR-21) were found to be involved in the pathological process of rheumatoid arthritis (RA), but the details were unclear. In this study, we aimed to clarify the relationship between IL-34 and miR-21 in RA. METHODS: IL-34 concentrations in serum and synovial fluid (SF) of patients with RA were measured by ELISA. Fibroblast-like synovial cells (FLS) were cultured for evaluation of STAT3 activation, miR-21, and Bax/Bcl-2 expression by Western blot and real-time PCR. Correlations were analyzed between clinical features and detectable variables including SF IL-34 levels and miR-21 expression. RESULTS: SF IL-34 levels were significantly higher in patients with RA who had a high 28-joint Disease Activity Score (DAS28 ≥ 3.2) than in those with a lower DAS28 (DAS28 < 3.2). DAS28 scores and miR-21 expression in FLS had a significant positive correlation with the SF IL-34 levels. In addition, IL-34 stimulation strengthened the activation of p-STAT3, resulting in the increment of miR-21 expression. Inhibiting of miR-21 expression contributed to decreased Bcl-2/Bax ratio, suggesting that miR-21 was involved in the resistance to apoptosis. With the blocking of the colony-stimulating factor-1 receptor (CSF1R), decreased protein expressions including CSF1R, p-STAT3/STAT3, and Bcl-2/Bax were shown, suggesting that CSF1R participated in the biological functions of IL-34 in RA. CONCLUSION: The IL-34/STAT3/miR-21 pathway is crucial for the survival of synovial fibroblasts in RA, which might be candidate therapeutic targets for RA treatment.
26885600 Changes in anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes ser 2016 May OBJECTIVES: Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a serological marker of rheumatoid arthritis (RA), and also have a prognostic value for more aggressive disease. Whether anti-CCP levels may change during treatment according to clinical response is matter of debate. Likewise, it is unknown whether different biological drugs have peculiar effects on anti-CCP levels. This study aimed to investigate changes in anti-CCP serum levels in RA patients on biological drugs with different mechanism of action. METHODS: We studied 71 patients with active RA tested positive for anti-CCP who started a first biological drug (54 anti-TNF-α drug, 9 rituximab, 8 tocilizumab). In 14 patients stopping anti-TNF-α treatment for ineffectiveness, rituximab was started. Anti-CCP and rheumatoid factor (RF) isotypes (IgM, IgA, IgG) levels were measured at entry, 12 months and again at 12 months after swapping to rituximab. RESULTS: After 1 year of therapy of the first biological drug, patients taking anti-TNF-α drugs showed a significant reduction of the anti-CCP levels (p=0.002), and all RF isotypes (p=0.003). Also patients treated with rituximab or tolicizumab had a significant decrease in anti-CCP (p=0.01) and RF isotype levels (p=0.01). Anti-CCP levels did not correlated with DAS28 over time. In patients switching to rituximab after failure of TNF-α blockers, anti-CCP levels did not change at 12 months (p=0.06), despite of the reduction of DAS28 (p=0.02) and RFs levels (p=0.02). CONCLUSIONS: Our study showed that anti-CCP levels may change during RA course, regardless of the biological drug used and the clinical response.
26546892 Th22 Cells Contribution in Immunopathogenesis of Rheumatic Diseases. 2015 Jun Newly identified T helper cell 22 (Th22) is a subset of CD4+T cells with specific properties apart from other known CD4+ T cell subsets with distinguished gene expression and function. Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-α (TNF-α). The levels of Th22 and related cytokine IL-22 are increased in various autoimmune diseases and positively associated with some rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, behcet's disease, ankylosing spondylitis and psoriatic arthritis. In summary, IL-22 and Th22 cells play a significant and complicated role in inflammatory and autoimmune rheumatic diseases, therefore, targeting IL-22 or Th22 have unique and attractive advantages due to the fact that Th22 subset is recently identified and its associated research is extremely limited. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of rheumatic disease.
26198292 The pathogenic role of angiogenesis in rheumatoid arthritis. 2015 Oct Angiogenesis is the formation of new capillaries from pre-existing vasculature, which plays a critical role in the pathogenesis of several inflammatory autoimmune diseases such as rheumatoid arthritis (RA), spondyloarthropathies, psoriasis, systemic lupus erythematosus, systemic sclerosis, and atherosclerosis. In RA, excessive migration of circulating leukocytes into the inflamed joint necessitates formation of new blood vessels to provide nutrients and oxygen to the hypertrophic joint. The dominance of the pro-angiogenic factors over the endogenous angiostatic mediators triggers angiogenesis. In this review article, we highlight the underlying mechanisms by which cells present in the RA synovial tissue are modulated to secrete pro-angiogenic factors. We focus on the significance of pro-angiogenic factors such as growth factors, hypoxia-inducible factors, cytokines, chemokines, matrix metalloproteinases, and adhesion molecules on RA pathogenesis. As pro-angiogenic factors are primarily produced from RA synovial tissue macrophages and fibroblasts, we emphasize the key role of RA synovial tissue lining layer in maintaining synovitis through neovascularization. Lastly, we summarize the specific approaches utilized to target angiogenesis. We conclude that the formation of new blood vessels plays an indispensable role in RA progression. However, since the function of several pro-angiogenic mediators is cross regulated, discovering novel approaches to target multiple cascades or selecting an upstream cascade that impairs the activity of a number of pro-angiogenic factors may provide a promising strategy for RA therapy.
27856318 Sympathetic nerve repulsion inhibited by designer molecules in vitro and role in experimen 2017 Jan 1 AIMS: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. MATERIALS AND METHODS: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2. All blocking molecules were tested in vitro using a sympathetic neurite outgrowth assay. CIA was induced by collagen type II in mice. KEY FINDINGS: In the neurite outgrowth assay, the two antibodies against plexin-A2 and neuropilin-2 as well as the four blocking peptides - two SEMA3F analogous peptides (WLFQRDPGDR, QATVKWLFQRDPGDRR) and two plexin A2 analogous peptides (DSSDQFSFDYELEQN, DSSIQFFSFEKDKERI) - were able to block sympathetic nerve fiber repulsion in vitro (at 150-600nmol/l). Administration of the two antibodies prophylactically on day 4 after immunization did not change clinical CIA. Similarly, using the top candidate antibody to plexin-A2 after CIA onset (mild score of 4 points, maximum=52 points), did not ameliorate CIA. The tested blocking peptides were not recovered in peripheral blood after i.v. and i.p. administration. SIGNIFICANCE: While designer molecules blocked nerve fiber repulsion in vitro, therapeutic administration in vivo did not change CIA. Possible strategies to overcome negative effects demonstrated in vivo are discussed.
26290589 Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and angiogen 2016 Jul INTRODUCTION: Acute-phase serum amyloid A (A-SAA) has cytokine-like properties and is expressed at sites of inflammation. We examined whether A-SAA-induced pro-inflammatory mechanisms are mediated through Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA). METHODS: The effect of A-SAA on human embryonic kidney (HEK), TLR2 or TLR4 cells was quantified by nuclear factor (NF)-κB luciferase reporter assays. A-SAA-induced RASFC and dHMVEC function were performed in the presence of a specific neutralising anti-TLR2 mAb (OPN301) (1 μg/mL) and matched IgG isotype control Ab (1 μg/mL). Cell surface expression of intracellular adhesion molecule (ICAM)-1, chemokine expression, cell migration, invasion and angiogenesis were assessed by flow cytometry, ELISA, Matrigel invasion chambers and tube formation assays. MyD88 expression was assessed by real-time PCR and western blot. RESULTS: A-SAA induced TLR2 activation through induction of NF-κB (p<0.05), but failed to induce NF-κB in HEK-TLR4 cells, confirming specificity for TLR2. A-SAA-induced proliferation, invasion and migration were significantly inhibited in the presence of anti-TLR2 (all p<0.05), with no significant effect observed for tumour necrosis factor-α-induced events. Additionally, A-SAA-induced ICAM-1, interleukin-8, monocyte chemoattractant protein-1, RANTES and GRO-α expression were significantly reduced in the presence of anti-TLR2 (all p<0.05), as was A-SAA induced angiogenesis (p<0.05). Finally, A-SAA induced MyD88 signalling in RASFC and dHMVEC (p<0.05). CONCLUSIONS: A-SAA is an endogenous ligand for TLR2, inducing pro-inflammatory effects in RA. Blocking the A-SAA/TLR2 interaction may be a potential therapeutic intervention in RA.
25438096 In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathy 2015 Jan OBJECTIVES: The objective of this study is to compare the serum levels of Dickkopf-1 (DKK1), a natural inhibitor of Wnt signalling, with parathyroid hormone (PTH) and bone involvement in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study includes 154 postmenopausal women with RA and 125 healthy controls. DKK1, 25OH vitamin D (25OHD), bone turnover markers, and PTH serum levels were measured by ELISA; lumbar spine and hip bone mineral density (BMD) and the erosion score were obtained. RESULTS: The RA patients and healthy controls were not significantly different in terms of age, body mass index, and 25OHD serum levels. The mean level of DKK1 and PTH were significantly higher in patients with RA than in healthy controls (172±68 [SD] vs. 96±55 pmoL/L, and 30±15 vs 22±11, respectively; p<0.0001). DKK1 serum levels were positively correlated with age (p<0.05) only in the healthy controls, while they were correlated with PTH serum levels only in the RA patients (p<0.0001). Among the RA patients, DKK1 levels adjusted for age, PTH and disease duration were significantly higher in patients with bone erosions (176 vs. 167 pmoL/L, respectively; p<0.05). DKK1 levels adjusted for age and PTH were negatively correlated with total hip BMD (p<0.05). In the RA patients not on treatment with bisphosphonates, DKK1 serum levels positively correlated with C-terminal telopeptides of type I collagene serum levels (p<0.05). CONCLUSIONS: In patients with RA, serum levels of DKK1 are significantly increased, correlate with PTH and are associated with increased risk of bone erosions and osteoporosis. However, this finding deserves confirmation in a larger and more selected population.
26608949 High-temporospatial-resolution dynamic contrast-enhanced (DCE) wrist MRI with variable-den 2016 Jan This study is to evaluate highly accelerated three-dimensional (3D) dynamic contrast-enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo-random variable-density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k-t SPARSE-SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti-tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow-up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm(3) and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28-ESR (r = -0.80, p < 0.05) and DAS28-CRP (r = -0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow-up (with DAS28-ESR r = -0.79, p < 0.05, and DAS28-CRP r = -0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses.
26987888 Drug-induced toxicity and patient reported outcomes in rheumatoid arthritis patients follo 2016 Apr AIM: While the introduction of the treat-to-target (T2T) strategy has been an important advance in the management of rheumatoid arthritis (RA), the potential for increased toxicity due to use of concurrent drugs could adversely affect patient reported outcomes (PROs). The objective was to determine whether the cessation of therapy due to toxicity affects long-term improvement in PROs in patients treated according to T2T strategy. METHODS: A total of 149 patients from an inception cohort of early RA were included. The occurrence and severity of toxicity were monitored at each visit over 3 years. PROs studied were function (measured using health assessment questionnaire); pain, fatigue and patient global assessment (PtGA) all assessed using a 100 mm visual analogue scale; helplessness and health-related quality of life (HRQoL). For each PRO, effect of drug withdrawal was measured by comparing mean change in PROs among patients with no/temporary vs. permanent withdrawal. In addition, effects of frequency of drug withdrawals, weeks to withdrawal and number of drugs withdrawn were analysed using linear regression. RESULT: After 3 years, 56 (37.4%) patients ceased at least one drug permanently due to toxicity. Patients with no/temporary withdrawal (n = 93) achieved significantly greater improvement in function (mean change = -0.54 vs. -0.31, p = 0.033), pain (mean change = -39.82 vs. -5.02, p = 0.018), fatigue (mean change = -29.14 vs. -14.76, p = 0.015) and PtGA (mean change = -29.64 vs. -17.00, p = 0.018) compared with their counterparts. Higher frequency of withdrawals was associated with lesser improvements in function, pain, fatigue and PtGA, while the number of drugs withdrawn and the weeks to withdrawal had lesser effects. However, the cessation of the drugs due to their toxicity did not have a significant association with HRQoL and helplessness. CONCLUSION: Improvements in function, pain, fatigue and PtGA at 3 years were diminished for patients who ceased drugs due to toxicity while broader measures of HRQoL were not affected.
27430176 Neutrophil/Lymphocyte Ratio in Patients with Rheumatoid Arthritis Treated with Biological 2016 BACKGROUND: Disease activity of rheumatoid arthritis (RA) is evaluated by composite measures, such as Disease Activity Score (DAS). Recently, much attention has been paid to a neutrophil-lymphocyte (N/L) ratio to evaluate the prognosis and the efficacy of intervention in various diseases. To determine whether the N/L ratio is a prognostic marker or a surrogate marker of response to biologics, this study investigated the N/L ratio in RA patients treated with biological agents. METHODS: The medical records were reviewed of 358 patients with RA in routine care who were treated with infliximab (144 patients), etanercept (120 patients), adalimumab (25 patients), tocilizumab (41 patients), or abatacept (28 patients). The 28-joint DAS (DAS28), a hemogram, erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein and matrix metalloproteinase 3 were assessed at baseline and 6 months after the treatment. RESULTS: The average N/L ratio significantly decreased from 5.9 at baseline to 4.5 6 months after the treatment. The N/L ratio and the DAS28-ESR, both at baseline and 6 months after the treatment, were modestly but significantly correlated. The N/L ratio was greater in patients with high disease activity than in patients with low disease sactivity. The change of the N/L ratio (ΔN/L) and the change of the DAS28-ESR were modestly but significantly correlated. Regarding the therapeutic response, the N/L ratio at baseline showed no significant difference between the response criteria; however, the N/L ratio after 6 months of treatment and the ΔN/L ratio differed significantly. The ΔN/L was also significantly correlated with the change of the serum level of C-reactive protein and the change of the DAS28-ESR. CONCLUSION: The N/L ratio is a marker of disease activity in RA. The ΔN/L ratio reflects the efficacy of biological agents but does not predict the response to biological agents.
27188731 Detection of the novel IL-1 family cytokines by QAH-IL1F-1 assay in rheumatoid arthritis. 2016 Apr 30 The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro-inflammatory cytokines (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β,IL-36γ) and 4 anti-inflammatory cytokines (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37 and IL-38), and play central roles in mediating immune responses. In this study, we detected serum levels of IL-36 subfamily cytokines (including IL-36α, IL-36β, IL-36γ, IL-36Ra and IL-38), IL-37, IL-33 and aimed to investigate the roles of these cytokines in rheumatoid arthritis (RA) preliminarily. A total of 10 RA patients and 10 healthy controls (HCs) were involved in this study, we measured IL-36 subfamily cytokines, IL-37 and IL-33 levels in the serum of the experiment subjects by QAH-IL1F-1 assay. Clinical and laboratory data of the subjects were collected and analyzed by Spearman's rank test. Compared to that of HCs, IL-36α, IL-36β, IL-36Ra, IL-38 and IL-33 levels were significantly increased in RA patients. We also found RA patients with elevated IL-36Ra had a higher ESR and RF-IgM, and there was a positive correlation between increased IL-36α and CRP. Our study suggests that parts of the novel members of IL-1 family cytokines were involved in the pathogenesis of RA, and may provide a novel target for therapies of RA.
26358095 Vitamin D receptor FokI, BsmI, and TaqI polymorphisms and susceptibility to rheumatoid ar 2016 Apr OBJECTIVE: The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). METHODS: Meta-analyses were conducted on the associations between the VDR FokI, BsmI, and TaqI polymorphisms and RA. RESULTS: A total of seven studies were considered in the meta-analysis, involving a total of 923 patients and 912 controls. Meta-analysis of the VDR FokI polymorphism showed no association between RA and the F allele in the entire studied cohort (odds ratio, OR = 1.1740, 95 % confidence interval, CI = 0.994-1.387, p = 0.059). However, stratification by ethnicity revealed a significant association between the F allele and RA in Europeans (OR = 1.402, 95 % CI = 1.126-1.746, p = 0.003). Furthermore, an association was found between RA and the VDR FokI polymorphism using both the dominant model and homozygote contrast. Meta-analysis revealed no association between RA and the VDR BsmI B and TaqI T polymorphisms in Europeans (OR for the B allele = 1.065, 95 % CI = 0.911-1.245, p = 0.427; OR for the T allele = 1.065, 95 % CI = 0.834-1.361, p = 0.613). CONCLUSION: This meta-analysis suggests that the VDR FokI polymorphism is associated with susceptibility to RA in European populations.
25990004 The age-risk relationship of hematologic malignancies in patients with rheumatoid arthriti 2015 Jul The risk of hematologic malignancies in rheumatoid arthritis (RA) patients has been an important clinical concern. The information of age effect on the interval from the diagnosis of RA to that of hematologic malignancies is limited. This study aimed to define the age-risk relationship between hematologic malignancies and RA. A retrospective cohort study was conducted nationwide with 17,472 patients and 87,360 controls from the Taiwan National Health Insurance Database covering 1997-2008. The subsequent development of hematologic malignancy was observed. The age-adjusted standardized incidence ratios (SIRs), incidence per 1000 person-years, follow-up duration for the diagnosis of hematologic malignancies, and cumulative hazard rates of hematologic malignancies between RA and controls were analyzed. Significantly higher incidences of both lymphoid and myeloid malignancies were found in male RA patients compared with RA-free patients (SIR 3.36, 95% CI = 2.03-5.57, and SIR: 3.69, 95% CI = 2.46-5.53). A significantly increased overall incidence risk was found in lymphoid malignancies (SIR 3.00, 95% CI = 2.22-4.05) but not significantly increased in myeloid malignancies (SIR 1.54, 95% CI = 0.95-2.50) in female RA. The follow-up duration for hematologic malignancies was significantly shorter in RA patients than in RA-free patients in both males and females (70.70 vs. 103.80 months and 67.73 vs. 100.93 months, respectively). Additionally, higher cumulative hazard rates in both lymphoid and myeloid malignancies were found in male RA patients (p < 0.0001). RA patients have a shorter incubation time to hematological malignancies while comparing to the RA-free people, and the risks are variable in gender and different age groups.
26940666 A multivariate method for meta-analysis and comparison of diagnostic tests. 2016 Sep 10 We present here an extension of the classic bivariate random effects meta-analysis for the log-transformed sensitivity and specificity that can be applied for two or more diagnostic tests. The advantage of this method is that a closed-form expression is derived for the calculation of the within-studies covariances. The method allows the direct calculation of sensitivity and specificity, as well as, the diagnostic odds ratio, the area under curve and the parameters of the summary receiver operator's characteristic curve, along with the means for a formal comparison of these quantities for different tests. There is no need for individual patient data or the simultaneous evaluation of both diagnostic tests in all studies. The method is simple and fast; it can be extended for several diagnostic tests and can be fitted in nearly all statistical packages. The method was evaluated in simulations and applied in a meta-analysis for the comparison of anti-cyclic citrullinated peptide antibody and rheumatoid factor for discriminating patients with rheumatoid arthritis, with encouraging results. Simulations suggest that the method is robust and more powerful compared with the standard bivariate approach that ignores the correlation between tests. Copyright © 2016 John Wiley & Sons, Ltd.
26158363 Repigmentation of hair following adalimumab therapy. 2015 Jun 16 Repigmentation of canities, or age-related grey or white hair, is a rare occurrence. Generalized repigmentation of grey-white hair has been reported following inflammatory processes, and heterochromia (localized patches of hair repigmentation) is even more unusual, reported in association with medication use and malignancy. Tumor necrosis factor (TNF) inhibitors are increasingly utilized medications for inflammatory disorders, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Hair loss, or alopecia, has been described among the side effects of these medications, but changes in hair pigmentation in association with this class of drugs have not previously been reported. We describe a patient with hair repigmentation associated with adalimumab therapy.
27118021 Early clinical response predicts low disease activity at one year in rheumatoid arthritis 2016 Dec OBJECTIVES: The aim of this study was to assess whether good EULAR response assessed at 3months may predict the achievement of low disease activity (LDA) at 1year in rheumatoid arthritis (RA) patients on treatment with certolizumab pegol (CZP). METHODS: From the nationwide Italian registry, we analysed 278 RA patients (age 54.8±12years, duration of disease 9.8±8years, female 84%) initiating CZP as first line (68%) or≥second line (32%) of biological treatment because of their active disease. Assessment of disease activity was based on 28 joint Disease Activity Score (DAS28). A reduction of DAS28>1.2 (good EULAR response) was assessed at 3months, and the achievement of LDA (DAS28≤3.2) was evaluated at 1year. Multiple regression models were used to estimate predictors of early good EULAR response or LDA. RESULTS: The percentages of patients attaining good EULAR response were 52% at 3, 65% at 6, and 66% at 12months. Furthermore, 51.2% (98/192) of the patients reached LDA at 12months. Patients taking CZP as first biological treatment had adjusted odds ratios (OR) of good EULAR response at 3months 6 folds higher than in those with≥1 prior biological drug (OR 6.7, 95% CI 1.97-23.1). While, the strongest variable correlating with 12months LDA was the achievement of good EULAR response at 3months (OR 11.3, 95% CI 13.1-34.8). CONCLUSIONS: Our findings showed that attaining good EULAR response at 3months strongly predicted 1year LDA in RA patients treated with CZP in real-life settings.