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ID PMID Title PublicationDate abstract
25213131 Impact of inadequate adherence on response to subcutaneously administered anti-tumour necr 2015 Mar OBJECTIVE: Non-adherence to DMARDs is common, but little is known about adherence to biologic therapies and its relationship to treatment response. The purpose of this study was to investigate the association between self-reported non-adherence to s.c. anti-TNF therapy and response in individuals with RA. METHODS: Participants about to start s.c. anti-TNF therapy were recruited to a large UK multicentre prospective observational cohort study. Demographic information and disease characteristics were assessed at baseline. Self-reported non-adherence, defined as whether the previous due dose of biologic therapy was reported as not taken on the day agreed with the health care professional, was recorded at 3 and 6 months following the start of therapy. The 28-joint DAS (DAS28) was recorded at baseline and following 3 and 6 months of therapy. Multivariate linear regression was used to examine these relationships. RESULTS: Three hundred and ninety-two patients with a median disease duration of 7 years [interquartile range (IQR) 3-15] were recruited. Adherence data were available in 286 patients. Of these, 27% reported non-adherence to biologic therapy according to the defined criteria at least once within the first 6-month period. In multivariate linear regression analysis, older age, lower baseline DAS28 and ever non-adherence at either 3 or 6 months from baseline were significantly associated with a poorer DAS28 response at 6 months to anti-TNF therapy. CONCLUSION: Patients with RA who reported not taking their biologic on the day agreed with their health care professional showed poorer clinical outcomes than their counterparts, emphasizing the need to investigate causes of non-adherence to biologics.
27419921 Chronic Conditions and Self-Reported Health in a Medicare Advantage Plan Population. 2017 Apr Self-reported changes in physical and mental health by members are an important dimension by which the quality of a Medicare Advantage (MA) plan is rated by the Centers for Medicare & Medicaid Services. To better target their interventions, MA plans need a better understanding of what observed characteristics-including clinical health conditions-predict self-reported changes in physical and mental health. This study explored how one MA plan's survey of participants' responses regarding changes in physical and mental health is associated with a set of chronic conditions as well as sociodemographic characteristics. Multinomial logistic regressions were used to examine the influence of 9 chronic conditions and age, sex, race, education, dual eligibility status (Medicare/Medicaid eligible), marital and living status, and assistance with survey completion on changes in patient-reported physical and mental health. Six conditions-dementia (P < 0.001), diabetes (P = 0.003), congestive heart failure (P = 0.002), cerebrovascular disease (P = 0.001), coronary artery disease (CAD) (P < 0.001), and rheumatoid arthritis (P < 0.001)-were associated with self-reported worsening of overall physical health. Four conditions-dementia (P < 0.002), diabetes (P = 0.047), CAD (P = 0.001), and decubitus ulcers (P = 0.033)-were associated with self-reported worsening of overall mental health. Females, married respondents, and those needing assistance with survey completion were more likely to report worsening of their mental health. Enrollees older than age 65 actually were less likely to report worsening of overall mental health. Findings provide insight into which members may be more susceptible to reporting that their physical or mental health is worsening.
26374404 Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic dr 2016 Jul OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. METHODS: Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. RESULTS: Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). CONCLUSIONS: TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ.
27067635 Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice. 2016 Jun Interleukin 22 (IL-22) expression is associated with increased joint destruction and disease progression in rheumatoid arthritis (RA). Although IL-22 is considered a pro-inflammatory cytokine, its mechanism of action in RA remains incompletely understood. Here, we used the collagen-induced arthritis model in IL-22 deficient (IL-22(-/-) ) mice to study the role of IL-22 in RA. In spite of normal disease incidence, disease severity is significantly diminished in IL-22(-/-) mice. Moreover, pathogenicity of Th17 cells and development and function of B cells are unaffected. In contrast, splenic plasma cells, as well as serum autoantibody titers, are reduced in the absence of IL-22. At the peak of disease, germinal centers (GCs) are severely reduced in the spleens of IL-22(-/-) mice, correlating with a decline in GC B-cell numbers. Within the GC, we identified IL-22R1 expressing follicular dendritic cell-like stromal cells. Human lymphoid stromal cells respond to IL-22 ex vivo by inducing transcription of CXCL12 and CXCL13. We therefore postulate IL-22 as an important enhancer of the GC reaction, maintaining chemokine levels for the persistence of GC reactions, essential for the production of autoantibody-secreting plasma cells. Blocking IL-22 might therefore prevent immune-complex deposition and destruction of joints in RA patients.
26521325 Rheumatoid Arthritis and Periodontal Disease. An Update. 2015 Aug A review of the epidemiological, pathological and immunological relationships between two chronic inflammatory diseases: rheumatoid arthritis (RA) and periodontal disease (PD). RA is a chronic inflammatory disease of the joints, characterized by loss of connective tissue and mineralized structures, the so-called "synovial membrane." Periodontitis is the inflammatory destruction of the periodontal attachment and alveolar bone. While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are similar. And it is possible that individuals manifesting both PD and RA may suffer from a unifying underlying systemic deregulation of the inflammatory response. There is an overproduction of a variety of cytokines and MMPs that appears to be common in both diseases. Oral health parameters should be more closely monitored in patients with RA, an autoimmune disease. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Interventions to prevent, minimize or treat periodontitis in arthritis patients will definitely promise a better quality of life for these patients.
27156396 Association Between Osteoprotegerin Gene Polymorphisms and Rheumatoid Arthritis Susceptibi 2016 Feb BACKGROUND AND AIMS: We undertook this study to assess the association between osteoprotegerin (OPG) gene polymorphisms and rheumatoid arthritis (RA) susceptibility. METHODS: English language databases of PubMed Medline and OVID EMBASE and Chinese databases of China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang were searched to identify case-control studies studied the relationship between OPG gene polymorphisms and RA susceptibility. Two reviewers separately and repeatedly screened searched studies according to study selection criteria and collected data. Data analyses of five comparison models-allelic model, heterozygote model, homozygote model, dominant model and recessive model-were conducted in Review Manager Software 5.1. RESULTS: A total of five studies including 1713 RA cases and 1845 controls were eligible in this meta-analysis. Single nucleotide polymorphisms (SNPs), rs3102735 T/C or A/G, rs2073618 G/C and rs3134069 T/G, of OPG gene were studied. Data from five studies of SNPs rs3102735 were OR = 1.22, 95% CI 0.86-1.73, OR = 1.06, 95% CI 0.86-1.32, OR = 1.79, 95% CI 0.65-4.89, OR = 1.16, 95% CI 0.85-1.59, OR = 1.73, 95% CI 0.67-4.46, respectively, for the five comparison models in order. For SNPs rs2073618, results derived from three studies were OR = 1.06, 95% CI 0.95-1.19, OR = 1.11, 95% CI 0.94-1.31, OR = 1.09, 95% CI 0.84-1.42, OR = 1.10, 95% CI 0.94-1.30, OR = 1.04, 95% CI 0.84-1.30, respectively. With respect to SNPs rs3134069, only one study assessed the associations, reporting no statistically significant results among the five comparison models. CONCLUSION: SNPs rs3102735, rs2073618 and rs3134069 of OPG gene polymorphisms are not susceptibility factors of RA based on currently available evidence.
27749216 On the history of gout: paleopathological evidence from the Medici family of Florence. 2017 Mar OBJECTIVES: Throughout history, gout has been referred to as the "disease of the kings", and has been clearly associated with the lifestyle of the aristocratic social classes. According to the written sources, several members of the famous Medici family of Florence suffered from an arthritic disease that contemporary physicians called "gout". A paleopathological study carried out on the skeletal remains of some members of the family, exhumed from their tombs in the Church of San Lorenzo in Florence, offered a unique opportunity to directly investigate the evidence of the arthritic diseases affecting this elite group. METHODS: The skeletal remains of several members of the family were examined macroscopically and submitted to x-ray investigation. RESULTS: The results of the study allowed us to ascertain that the so-called "gout of the Medici" should be considered the clinical manifestation of three different joint conditions: diffuse idiopathic skeletal hyperostosis, rheumatoid arthritis and uratic gout. In particular, uric acid gout was diagnosed in the Grand Duke Ferdinand I (1549-1609). Recently, a new case of this disease was diagnosed in Anton Francesco Maria (1618-1659), a probable illegitimate member of the family. CONCLUSIONS: With this new case, uratic gout was observed in 2 out of 9 adult males, leading to suppose that the disease should have been a common health problem within the family. The aetiology of the disease has to be searched in environmental factors, since both historical and paleonutritional studies demonstrated that the diet of this aristocratic court was rich in meat and wine.
26608926 Mannose-binding lectin polymorphisms and rheumatoid arthritis: A short review and meta-ana 2016 Jan Mannose-binding lectin (MBL) is a pattern recognition receptor of the lectin pathway of complement system. MBL binds to carbohydrates on microorganism's surfaces leading to complement activation, opsonization and phagocytosis. Polymorphisms in the MBL gene (MBL2) are associated with variations on MBL serum levels and with the susceptibility to various infectious and autoimmune diseases. The involvement of the lectin pathway in rheumatoid arthritis (RA) has been demonstrated by several studies and although MBL has been considered to have a dual role in the pathogenesis of the disease, the association between MBL and RA remains inconclusive. In an attempt to clarify this relationship, we developed this short review summarizing accumulated evidences in regard to MBL and RA and a meta-analysis to evaluate the influence of MBL2 polymorphisms on the susceptibility to RA. Among a total of 217 articles that were identified following a predefined search strategy on PubMed, Scopus, Scielo, EMBASE and Cochrane databases, only 13 met all inclusion criteria and were included in the meta-analysis. Data assessment was conducted by three independent investigators and presented in odds ratio (OR) and 95% confidence intervals (CIs) using forest plot charts. Both heterogeneity and publication bias were analyzed. The results of the meta-analysis evidenced that MBL2 low producing OO and XX genotypes do not confer higher risk to RA, even when data were analyzed according to cohort's ethnicity. Further studies are needed in order to clarify the importance of other genes of the lectin pathway in the pathogenesis of RA.
26130274 The comparative effectiveness of biologics among older adults and disabled rheumatoid arth 2015 Dec AIMS: Older and disabled rheumatoid arthritis (RA) patients are often not present in large numbers in clinical trials or registries. A novel, claims-based clinical effectiveness algorithm provides the potential to compare the effectiveness of different biologics among this population using large administrative databases. METHOD: Using Medicare 2006-2010 data for 100% of patients with RA, we identified biologic naïve users of abatacept, adalimumab, etanercept and infliximab, defined as no biologic use during the 12 months before the biologic initiation. The effectiveness was evaluated at 365 days after biologic initiation, determined using a validated claims-based algorithm. We compared the proportion meeting effectiveness criteria for each biologic using robust Poisson regression to compute risk ratios (RRs) adjusted for potential confounders. One year cost per effectively treated patient was calculated by different biologics. RESULTS: The study included biologic naïve users of abatacept (n = 2129), adalimumab (n = 2944), etanercept (n = 3517) and infliximab (n = 5654). The algorithm classified the medications as 26% effective for abatacept, 24% for adalimumab, 28% for etanercept and 23% for infliximab, indicating comparable effectiveness. However, after adjustment and compared with infliximab, the RRs for effectiveness were 1.17 (95% CI 1.06, 1.30) for abatacept, 1.11 (95% CI 1.02, 1.23) for adalimumab and 1.27 (95% CI 1.17, 1.39) for etanercept. Older patients had a higher effectiveness than patients who were disabled (RR = 1.18, 95% CI 1.08, 1.28). Infliximab had highest cost per effectively treated patient. CONCLUSION: Abatacept, adalimumab and etanercept are more effective than infliximab among RA patients initiating biologics. Effectiveness was significantly higher among older patients compared with disabled RA Medicare patients.
26131871 Interstitial granulomatous dermatitis: rare cutaneous manifestation of rheumatoid arthriti 2015 May Besides being an uncommon clinicopathological entity, interstitial granulomatous dermatitis, also described as interstitial granulomatous dermatitis with arthritis (IGDA), has shown a wide spectrum of clinical manifestations, such as linear and erythematous lesions, papules, plaques and nodules. Histological features include dense dermal histiocytic infiltrate, usually in a palisade configuration, and scattered neutrophils and eosinophils. We describe a middle aged woman with rheumatoid arthritis of difficult management and cutaneous lesions compatible with IGDA.
27878579 G protein coupled receptors signaling pathways implicate in inflammatory and immune respon 2017 May INTRODUCTION: G protein-coupled receptors (GPCRs) are transmembrane receptor proteins, which allow the transfer of signals across the membrane. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. GPCRs signaling pathways play a significant role in inflammatory and immune response processes including RA. FINDINGS: In this review, we have focused on the advances in GPCRs signaling pathway implicating the inflammatory and immune response of RA. The signaling pathways of GPCRs-adenylyl cyclase (AC)-cyclic adenosine 3', 5'-monophosphate (cAMP) include β(2) adrenergic receptors (β(2)-ARs)-AC-cAMP signaling pathways, E-prostanoid2/4 (EP2/4)-AC-cAMP signaling pathways and so on. Regulatory proteins, such as G protein-coupled receptor kinases (GRKs) and β-arrestins, play important modulatory roles in GPCRs signaling pathway. GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response. CONCLUSION: GPCRs-AC-cAMP signal pathways involve in the inflammatory and immune response of RA. Different signaling pathways are mediated by different receptors, such as β(2)-AR, PGE2 receptor, chemokines receptor, and adenosine receptor. GRKs and β-arrestins are crucial proteins in the regulation of GPCRs signaling pathways. The potential therapeutic targets as well as strategies to modulate GPCRs signaling pathway are new development trends.
27671860 MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis. 2016 Sep 27 MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD(-)CD27(-) memory B-cell population in ACPA(+) RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA.
28502142 APRIL Level as a Marker of Disease Activity in Treated Rheumatoid Arthritis Patients: Asso 2015 Jun Rheumatoid arthritis (RA) is a chronic autoimmune disease with joint inflammation and autoantibody production. Cytokines play an important role in the pathogenesis of RA. Among the cytokines that regulate B cell homeostasis is the "A Proliferation-Inducing Ligand" (APRIL). To determine the differences in APRIL in response to treatment in anti- cyclic citrllinated peptides (anti-CCP) positive versus anti-CCP negative patients with established RA. Concentrations of APRIL in sera of 10 anti-CCP positive RA patients, 18 anti-CCP negative RA patients, and 12 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA) at treatment initiation and after 6 months of treatment with methotrexate and hydroxychloroquine. Correlations between serum anti-CCP, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), and serum level of APRIL were analyzed. Serum APRIL levels were increased in rheumatoid arthritis patients in comparison with healthy volunteers. APRIL correlated positively with disease activity; swollen joint count, visual analog score and simplified disease activity index (all P < 0.05). In addition, APRIL was significantly higher in patients with positive anti-CCP. After treatment, APRIL levels significantly decreased in the anti-CCP positive RA patients than in anti-CCP negative RA patients. In conclusions, serum APRIL may be a good predictor marker for joint injury and therapeutic response in patients with RA.
26991546 Using propensity score adjustment method in genetic association studies. 2016 Jun BACKGROUND: The statistical tests for single locus disease association are mostly under-powered. If a disease associated causal single nucleotide polymorphism (SNP) operates essentially through a complex mechanism that involves multiple SNPs or possible environmental factors, its effect might be missed if the causal SNP is studied in isolation without accounting for these unknown genetic influences. In this study, we attempt to address the issue of reduced power that is inherent in single point association studies by accounting for genetic influences that negatively impact the detection of causal variant in single point association analysis. In our method we use propensity score (PS) to adjust for the effect of SNPs that influence the marginal association of a candidate marker. These SNPs might be in linkage disequilibrium (LD) and/or epistatic with the target-SNP and have a joint interactive influence on the disease under study. We therefore propose a propensity score adjustment method (PSAM) as a tool for dimension reduction to improve the power for single locus studies through an estimated PS to adjust for influence from these SNPs while regressing disease status on the target-genetic locus. The degree of freedom of such a test is therefore always restricted to 1. RESULTS: We assess PSAM under the null hypothesis of no disease association to affirm that it correctly controls for the type-I-error rate (<0.05). PSAM displays reasonable power (>70%) and shows an average of 15% improvement in power as compared with commonly-used logistic regression method and PLINK under most simulated scenarios. Using the open-access multifactor dimensionality reduction dataset, PSAM displays improved significance for all disease loci. Through a whole genome study, PSAM was able to identify 21 SNPs from the GAW16 NARAC dataset by reducing their original trend-test p-values from within 0.001 and 0.05 to p-values less than 0.0009, and among which 6 SNPs were further found to be associated with immunity and inflammation. CONCLUSIONS: PSAM improves the significance of single-locus association of causal SNPs which have had marginal single point association by adjusting for influence from other SNPs in a dataset. This would explain part of the missing heritability without increasing the complexity of the model due to huge multiple testing scenarios. The newly reported SNPs from GAW16 data would provide evidences for further research to elucidate the etiology of rheumatoid arthritis. PSAM is proposed as an exploratory tool that would be complementary to other existing methods. A downloadable user friendly program, PSAM, written in SAS, is available for public use.
26295713 In Vitro Validation of an Artefact Suppression Algorithm in X-Ray Phase-Contrast Computed 2015 X-ray phase-contrast tomography can significantly increase the contrast-resolution of conventional attenuation-contrast imaging, especially for soft-tissue structures that have very similar attenuation. Just as in attenuation-based tomography, phase contrast tomography requires a linear dependence of aggregate beam direction on the incremental direction alteration caused by individual voxels along the path of the X-ray beam. Dense objects such as calcifications in biological specimens violate this condition. There are extensive beam deflection artefacts in the vicinity of such structures because they result in large distortion of wave front due to the large difference of refractive index; for such large changes in beam direction, the transmittance of the silicon analyzer crystal saturates and is no longer linearly dependent on the angle of refraction. This paper describes a method by which these effects can be overcome and excellent soft-tissue contrast of phase tomography can be preserved in the vicinity of such artefact-producing structures.
27966336 Anticyclic citrullinated peptide antibody in rheumatoid arthritis:a cross-sectional study 2016 Nov 17 BACKGROUND/AIM: Studies have shown that anticyclic citrullinated peptide antibody (anti-CCP) titers can be useful in the diagnosis of rheumatoid arthritis (RA). We evaluate the association between anti-CCP antibody titers and the demographic, clinical, and laboratory characteristics of RA patients. Moreover, we explore whether there is any relation between joint destruction and demographic and clinical characteristics of RA patients. MATERIALS AND METHODS: One hundred and four RA patients with positive anti-CCP titers were compared to 104 RA patients with negative anti-CCP titers. The activity of RA was evaluated using the Disease Activity Score 28 (DAS28). Joint destruction was assessed in the subjects by X-rays of the wrists. Blood samples were collected for assessment of anti-CCP, rheumatoid factor (RF), and erythrocyte sedimentation rate. RESULTS: Forty-eight (23.0%) males and 160 (76.9%) females were included in this study. RF, DAS28, and joint destruction were significantly different between patients with and without anti-CCP (P < 0.0001). DAS28, duration of disease, hospitalizations, and occupation differed significantly between patients with and without joint destruction (P < 0.0001). CONCLUSION: This study indicates that anti-CCP is correlated with a high disease activity index and more joint destruction in RA patients and it may be used as a prognostic factor for RA.
26750560 Do Rheumatoid Arthritis Patients Rate their Health Status Different than their Caregivers? 2015 OBJECTIVE: To compare the ratings given by the caregivers regarding the health status of their rheumatoid arthritis (RA) patients to those recorded by the patients themselves and to assess the effect of caring for a patient with RA on the mental health of the caregiver. METHODS: This is a non-interventional, cross-sectional, multi-center epidemiological study conducted at the outpatient clinics of two hospitals in Saudi Arabia. The patients included were diagnosed with RA, over 18 years of age with 1-5 years of disease duration, and all had an identifiable single caregiver who was willing to participate in the study. RESULTS: 40 patients of whom 92.5% were women and the mean age of 44.6 years. The mean visual analogue scale (VAS) score was 4.98 for general health. The mean Health Assessment Questionnaire (HAQ) for the patients according to themselves was 1.31 (±0.68), while that stated by caregivers was 1.40 (±0.69); thus, the mean scores given by the caregivers was 0.091 points higher than that provided by the patients themselves (95% confidence interval [CI], 0.167-0.014) (p=0.0214). Further, 43% of the caregivers gave higher HAQ scores to their related patients than the patients themselves, while 30% gave similar HAQ scores. The caregivers scored a mean of 21 points in the Zarit Burden Interview (±12.1), with 47.5% reporting mild to moderate burden, and 5% reporting moderate to severe burden. CONCLUSION: RA patients showed a tendency to understate their disease burden and as compared to that observed by caregivers who suffer from considerable level of burden.
27812008 IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an I 2016 Nov 4 IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4(+) T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.
25776112 Disease activity in rheumatoid arthritis and the risk of cardiovascular events. 2015 Jun OBJECTIVE: Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease activity in RA correlates with CV events. METHODS: We studied patients with RA whose cases were followed in a longitudinal US-based registry. Time-averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes. RESULTS: A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person-years (95% confidence interval [95% CI] 6.7-8.9). In models adjusted for variables noted above, a 10-point reduction in the time-averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13-29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable. CONCLUSION: Our findings showed that reduced time-averaged disease activity in RA is associated with fewer CV events.
26255186 Clinical and laboratory factors associated with interstitial lung disease in rheumatoid ar 2015 Sep OBJECTIVE: The objective of this study is to examine the clinical, genetic, and environmental factors associated with interstitial lung disease (ILD) in rheumatoid arthritis (RA). METHOD: We recruited patients with RA from rheumatology practices at the time of a scheduled visit. Each patient participated in a comprehensive assessment that included ascertainment of age, sex, joint tenderness and swelling, subcutaneous nodules, disease severity, use of methotrexate and prednisone, smoking status, rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP),erythrocyte sedimentation rate (ESR), the 28-joint Disease Activity Score (DAS28), and the presence of the HLA-DRB1 shared epitope (SE). As part of a thorough quantification of comorbidity, we identify all comorbid conditions, including ILD. We examined variables associated with ILD using logistic regression. We tested interaction terms between SE and other covariates. RESULTS: We studied 779 RA patients, among whom, ILD was recognized clinically in 69 (8.8 %). Variables significantly associated with ILD in a multivariable analysis included male sex, RA duration, the ESR, the DAS28, anti-CCP, and RF. There was a significant interaction between the HLA-DRB1 SE and smoking, ILD being associated with smoking only in the presence of SE. The association between ILD and anti-CCP, RF, and the ESR displayed a biological gradient, higher titers being more strongly associated with ILD. CONCLUSION: Anti-CCP antibodies and the RF may be pathogenically related to ILD. The association between ILD and smoking is dependent on the HLA-DRB1 SE, which may reflect gene-environment interaction.