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ID PMID Title PublicationDate abstract
27510601 Association between antiphospholipid antibodies and arterial thrombosis in patients with r 2017 Jan OBJECTIVES: Antiphospholipid antibodies (aPL) are present in a proportion of patients with rheumatoid arthritis but their clinical significance remains unclear. We investigated the association between aPL and thrombotic events in rheumatoid arthritis patients. METHODS: In this cross-sectional study, aPL profiles were evaluated in 376 rheumatoid arthritis patients in accordance with the standard guidelines. Clinical and radiographic data were retrospectively collected. RESULTS: aPL were identified in 39 patients (10.4%). Lupus anticoagulant was the most common subtype (n = 25, 6.6%); anti-cardiolipin antibodies and anti-β(2) glycoprotein I antibodies were detected in six and 12 patients (1.6% and 3.2%), respectively. Compared to the aPL-negative group, aPL-positive patients included more male patients (41.0% vs. 15.4%, P < 0.001) and more smokers (41.0% vs. 16.0%, P = 0.001). There was no difference between the two groups in age, disease duration and body mass index, or the frequency of diabetes, hypertension or dyslipidaemia. Of note, arterial thromboses were more common in the aPL-positive than the aPL-negative group (12.8% vs. 2.1%, P = 0.004), whereas the frequency of venous thrombosis did not differ between the two groups (0.0% vs. 0.9%, P = 1.000). On multivariate regression analysis, aPL, age, hypertension, dyslipidaemia and baseline C-reactive protein level were independently associated with arterial thrombotic events (all P values < 0.05). CONCLUSION: aPL was found in a subset of rheumatoid arthritis patients, who were more often smokers, and aPL was independently associated with development of arterial thrombosis. This result suggests that aPL may contribute to an increased risk of arterial thrombosis in rheumatoid arthritis patients.
25995669 Sleep quality in rheumatoid arthritis, and its association with disease activity in a Kore 2015 May BACKGROUND/AIMS: The aim of this study was to compare the sleep quality between rheumatoid arthritis (RA) patients and healthy controls; and to evaluate the relationship between RA disease activity and sleep quality in Korea. METHODS: A total of 130 RA patients and 67 age- and sex-matched healthy controls were enrolled in a comparative study of sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Age, gender, concomitant medication, erythrocyte sedimentation rate, serum C-reactive protein, Beck Depression Inventory second edition (BDI-II), 28 joints disease activity score (DAS28), pain visual analog scale (VAS), and PSQI were analyzed as covariates. We also analyzed the sleep quality of RA patients according to the disease activity (DAS28 ≤ 3.2, 3.2 < DAS28 < 5.1, and DAS28 ≥ 5.1, respectively). RESULTS: The total PSQI score and the frequency of poor sleep quality, were higher in the RA patients (5.62 ± 4.19, 38.5%) than in the control subjects (3.57 ± 2.17, 13.4%). The patients with poor sleep quality (PSQI > 5) were older and had a higher BDI-II and VAS score than the patients without sleep disturbance (PSQI ≤ 5). The score in subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, total PSQI, and frequency of poor sleep quality were increased when RA activity was high. CONCLUSIONS: Sleep disturbance was observed in RA patients (38.5%), and high RA disease activity was associated with poor sleep quality in Korea.
27354069 What evidence is there for a delay in diagnostic coding of RA in UK general practice recor 2016 Jun 28 OBJECTIVES: Much research with electronic health records (EHRs) uses coded or structured data only; important information captured in the free text remains unused. One dimension of EHR data quality assessment is 'currency' or timeliness, that is, data are representative of the patient state at the time of measurement. We explored the use of free text in UK general practice patient records to evaluate delays in recording of rheumatoid arthritis (RA) diagnosis. We also aimed to locate and quantify disease and diagnostic information recorded only in text. SETTING: UK general practice patient records from the Clinical Practice Research Datalink. PARTICIPANTS: 294 individuals with incident diagnosis of RA between 2005 and 2008; 204 women and 85 men, median age 63 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Assessment of (1) quantity and timing of text entries for disease-modifying antirheumatic drugs (DMARDs) as a proxy for the RA disease code, and (2) quantity, location and timing of free text information relating to RA onset and diagnosis. RESULTS: Inflammatory markers, pain and DMARDs were the most common categories of disease information in text prior to RA diagnostic code; 10-37% of patients had such information only in text. Read codes associated with RA-related text included correspondence, general consultation and arthritis codes. 64 patients (22%) had DMARD text entries >14 days prior to RA code; these patients had more and earlier referrals to rheumatology, tests, swelling, pain and DMARD prescriptions, suggestive of an earlier implicit diagnosis than was recorded by the diagnostic code. CONCLUSIONS: RA-related symptoms, tests, referrals and prescriptions were recorded in free text with 22% of patients showing strong evidence of delay in coding of diagnosis. Researchers using EHRs may need to mitigate for delayed codes by incorporating text into their case-ascertainment strategies. Natural language processing techniques have the capability to do this at scale.
27601627 Low-density granulocytes: functionally distinct, immature neutrophils in rheumatoid arthri 2017 Feb Our aim was to determine whether rheumatoid arthritis (RA) low-density granulocytes (LDGs) are functionally different from RA neutrophils. LDGs from 32 RA patients were characterized using flow cytometry and quantitative PCR (qPCR). RNA sequencing (RNA-Seq) was carried out on paired RA LDGs and neutrophils (n = 4) and validated using qPCR. Functional assays included chemotaxis, phagocytosis, reactive oxygen species (ROS) production, cell-cycle analysis, apoptosis, neutrophil extracellular trap (NET)osis, and measurement of cytokine production (n ≥ 5 paired RA LDGs/neutrophils). RA LDGs had a substantially altered transcriptome, expressing >5000 genes at significantly different levels compared with RA neutrophils, including elevated levels of transcripts for granule proteins [including elastase and myeloperoxidase (MPO)] and cell-cycle genes [including cyclin-dependent kinase (CDK)2, CDK4, and CDK6]. Approximately 1% of RA LDGs stained positive for the G2/S phase of the cell cycle. RA LDGs had a significantly lower constitutive rate of apoptosis compared with RA neutrophils and did not respond to TNF-α in culture. Expression of transcripts for cytokines and cytokine receptors was lower in RA LDGs. NET formation was lower in LDGs in response to PMA compared with RA neutrophils. Chemotaxis and phagocytosis was lower in RA LDGs compared with neutrophils. RA LDGs produced significantly lower amounts of ROS in response to fMLP following priming with TNF-α. Expression of TNFR1 and -2 mRNA and protein was significantly lower in LDGs. We conclude that RA LDGS are functionally different from RA neutrophils, representing an immature neutrophil population within peripheral blood. Their enhanced survival properties and decreased TNF signaling are likely to have important consequences for disease pathology and response to therapy.
26718437 Associations between interleukin-1 and IL-1 receptor antagonist polymorphisms and suscep 2015 Dec 26 This study determined whether interleukin-1 (IL-1) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-1A, IL-1B, and IL-1 receptor antagonist (IL-1RN) polymorphisms and RA. A total of 16 studies involving 4,339 RA cases and 3,885 controls were included in the meta-analysis. Meta-analysis of the IL-1B -511 C/T polymorphism revealed an association between the IL-1B -511 T allele and RA in Caucasians (OR = 0.913, 95% CI = 0.840-0.992, p = 0.031), but not in Asians. Ethnicity-specific meta-analysis indicated an association between the TT+TC genotype of the IL-1B 3953 C/T polymorphism and RA in Caucasians (OR = 1.243, 95% CI = 1.008-1.533, p = 0.042) and in Asians (OR = 2.672, 95% CI = 1.662-4.296, p = 4.9x10-6). No association was between RA susceptibility and the IL-1A -889 C/T, IL-1A +4845 G/T, and IL-1RN +2018 C/T polymorphisms. This meta-analysis suggests the IL-1B -511 C/T polymorphism is associated with susceptibility to RA in Caucasians, and that the IL-1B +3953 C/T polymorphism is associated with susceptibility to RA in Caucasians and Asians.
25797915 Relationship between endothelial dysfunction and osteoprotegerin, vitamin D, and bone mine 2015 Mar OBJECTIVES: We aimed to investigate whether the abnormalities in bone mineral density (BMD) that occur in patients with rheumatoid arthritis (RA) are associated with the presence of endothelial dysfunction. METHODS: Cross-sectional study encompassing 216 subjects (111 patients with RA and 105 age- and sex-matched controls) without history of cardiovascular disease. Endothelial function was determined by brachial artery flow-mediated dilatation (FMD) and BMD by dual x-ray absorptiometry (DXA) measurements. Plasma vitamin D and osteoprotegerin serum (OPG) levels were assessed in patients and controls. Multiple regression analysis was performed to study the relationship between BMD with endothelial function, taking into account vitamin D and OPG levels. RESULTS: After adjusting for traditional cardiovascular risk factors, vitamin D and OPG levels, BMD emerged as an independent factor associated with lower FMD values in controls, but not in patients with RA. Although OPG levels were inversely associated with FMD values in both RA patients and controls after adjusting for BMD, vitamin D showed this relationship only in the controls. CONCLUSIONS: Whilst OPG is associated with endothelial function in RA patients and controls, vitamin D levels and BMD are related to endothelial function in controls but not in patients with RA.
24399234 Comparison of the long-term outcome for patients with rheumatoid arthritis with persistent 2015 Apr OBJECTIVE: To investigate if patients with early RA with persistent moderate disease activity during the first year after diagnosis have a worse 3-5 year outcome than those who achieve sustained clinical remission within the first year, in a daily life setting. METHODS: The ESPOIR cohort included patients with early arthritis of <6 months' duration. Treatment was the standard of care. We had 5-year follow-up data for 573 patients. This study compared patients who had persistent moderate disease activity (Disease Activity Score in 28 joints (DAS28)>3.2 and ≤5.1) at both the 6- and 12-month visits, with those who were in sustained DAS28 remission. The primary outcome was radiographic progression at the 36-month visit. Secondary endpoints were clinical remission (DAS28 score, Simplified Disease Activity Index, ACR/EULAR criteria), Health Assessment Questionnaire-Disability Index (HAQ-DI) and number of missed workdays at months 36 and 60. A Fisher exact test was used to compare categorical variables, and the Kruskal-Wallis test for quantitative variables. Logistic regression analysis was used to determine predictors of outcome. RESULTS: Patients were aged 48.1±12.5 years and their duration of symptoms was 103.2±52.1 days. Mean baseline DAS28 was 5.1±1.3. Persistent moderate disease activity (107 patients) rather than sustained remission (155 patients) during the first year was associated with increased radiographic disease progression at 3 years (OR=1.99 (95% CI 1.01 to 3.79)), increased HAQ-DI at 3 and 5 years (5.23 (2.81 to 9.73) and 4.10 (2.16 to 7.80), respectively), a 7-11 times smaller chance of achieving clinical remission and a five times greater number of missed workdays. CONCLUSIONS: Patients with early RA with persistent moderate disease activity during the first year had a worse outcome than patients who achieved sustained clinical remission. Persistent moderate disease activity affects long-term structure, remission rate and functional and work disability. Such patients may benefit from intensive treatment.
27686747 Neutrophil-to-lymphocyte ratio is a reliable marker of treatment response in rheumatoid ar 2017 May OBJECTIVE: To investigate the reliable markers reflecting treatment response better than the traditional inflammatory indices in patients with rheumatoid arthritis (RA) receiving tocilizumab therapy. METHODS: A total of 58 RA patients treated with tocilizumab for more than six months from January 2013 to December 2014 were initially included. Flares were defined as events that required steroid dose escalation, intra-articular steroid injections, or switching tocilizumab to other biologic agents. The clinical and laboratory data were retrospectively collected from electronic medical records. RESULTS: Of the 52 patients except for six patients who were excluded, 16 experienced flares, and 36 were stable during tocilizumab therapy. The C-reactive protein (CRP) level did not significantly differ between a stable state before flares and at flares. Compared with those at the preflare time point, erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) were significantly higher at flares; however, ESR levels (n = 9) were within the normal limit or decreased (n = 4) at flares. Interestingly, NLR increased at flares in all but one patient in the flare group. CONCLUSION: NLR is a more reliable marker than ESR or CRP for evaluating the disease activity in patients with RA during tocilizumab therapy.
28033292 Bortezomib followed by autologous stem cell transplantation in a patient with rheumatoid a 2016 Dec RATIONALE AND PATIENTS CONCERNS: Despite the introduction of varied disease-modifying antirheumatic drugs and biological agents, a substantial proportion of patients remain untreatable. We report a 56-year-old Chinese female patient with a case of refractory rheumatoid arthritis (RA) complicated with multiple myeloma (MM) who was treated successfully with Bortezomib followed by autologous stem cell transplantation (ASCT). DIAGNOSIS AND INTERVENTIONS: We report a 56-year-old Chinese female patient who was diagnosed as RA complicating with MM. She received 4 cycles of Bortezomib-based chemotherapy followed by ASCT. The response of her RA and MM were evaluated after every cycle of Bortezomib-based chemotherapy. INTERVENTIONS AND OUTCOMES: After the first Bortezomib-based chemotherapy cycle, this patient's symptoms were significantly alleviated and thereafter the RA activity continued to improve. After the 4 courses of Bortezomib-based chemotherapy, the C-reactive protein was <0.5 mg/dL and the disease activity score 28-erythrocyte sedimentation rate was 2.0. No hematological or nonhematological side effects were observed during the treatment of Bortezomib. LESSONS: Bortezomib might be a new safe and promising drug for refractory RA patients.
25588372 Current cigarette use in rheumatoid arthritis patients: associated factors and a limited m 2015 Jul Some newly published studies revealed that current smoking was associated with accelerated disease progression in diagnosed rheumatoid arthritis (RA) patients. The major aims of this study were to analyze the associated factors of current smoking in RA patients and explore the mediating role of depression in the associations between identified factors and smoking. RA patients were selected from NHANES databases 2005-2012. Current smoking was determined by race-specific serum cotinine levels. Depression was measured by the Depression Screener questionnaire. Totally, 848 RA patients were identified and included into final analysis. Logistic regression model founds that age, race, and socioeconomic status (SES) were associated with current smoking in RA patients: the odds ratios (ORs) of smoking were 0.29 (95 % CI 0.17, 0.49) and 0.39 (95 % CI 0.24, 0.62) in patients over 60 years old and of higher SES, respectively; non-Hispanic white patients with a pre-RA smoking history had an OR of 3.48 (95 % CI 1.35, 5.18) when compared with patients of other race with no pre-RA smoking history. Structural equation model identified a weak mediating role of depression, only accounted for 5 % of the total SES-smoking association. In this sample of diagnosed RA patients, age, SES, ethnicity, but not depression, were significantly associated with current smoking.
26481198 Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: A 2017 Jul AIM: The aim of this exploratory study is to estimate the relationship between vitamin D (vit D) deficiency and active rheumatoid arthritis (RA), and the role of supplementation in improving disease activity. METHOD: A randomized recruitment, consent screening, open-label interventional study was conducted in patients who fulfilled American College of Rheumatology/European League Against Rheumatism 2010 criteria for diagnosing RA and on stable disease-modifying anti-rheumatic drugs (DMARDs) for 3 months. Serum vit D levels and Disease Activity Score of 28 joints/C-reactive protein (DAS28-CRP) disease activity status were estimated at the first visit. Subjects with low vit D levels and DAS28-CRP > 2.6 were supplemented with vit D for 12 weeks, and were assessed for improvement in disease activity and serum vit D levels. RESULTS: One hundred and fifty RA patients of mean age 49 ± 12.1 years, mean duration of illness 78 ± 63 months, and on treatment with DMARDs for 44 ± 39 months were recruited for the study. Of these, 73 (49%) subjects were found to have DAS28-CRP > 2.6 and serum vit D below 20 ng/mL. The patients received vit D supplement of 60 000 IU/week for 6 weeks, followed by 60 000 IU/month for a total duration of 3 months. Disease activity and vit D status were assessed for 59 (80.8%) patients who reported at the end of 12 weeks of treatment. Mean DAS28-CRP of these patients showed a statistically significant improvement from 3.68 ± 0.93 at baseline to 3.08 ± 1.11 after supplementation (P = 0.002). Serum vit D levels improved from 10.05 ± 5.18 to 57.21 ± 24.77 ng/mL (P < 0.001) during the period. CONCLUSION: Supplementation of vit D in RA patients with persisting disease activity and vit D deficiency contributed to significant improvement in disease activity within a short duration.
27136756 Self-Reported Barriers to Healthcare Access for Rheumatoid Arthritis Patients in Rural and 2016 Dec OBJECTIVES: The aim of the present study was to identify potential barriers for access to medical and allied health services from the perspective of rural and Northern Saskatchewan rheumatoid arthritis (RA) patients. METHODS: A total of 100 adults with established RA, residing in rural and Northern Saskatchewan, were recruited from two rheumatology practices. Structured interviews with standardized scripts solicited patient perspectives on appointment waiting times, travel required to access medical services and satisfaction with healthcare provision. Thematic analysis was employed for qualitative data. RESULTS: Patients-reported concerns regarding waiting time for their first rheumatology appointment. There was reduced access to allied health professionals, with only 53% of the participants having seen a physiotherapist (PT), and only 26% an occupational therapist (OT). Patients had similar driving distances to their family physician, PT, pharmacy and laboratory services but commuted significantly further for rheumatologist and OT services. There were high levels of satisfaction with their rheumatologist and family physician appointments (8.96 and 8.04 on a ten-point scale). Patients with longer travel times had higher satisfaction with their health care appointments: Patients who travelled one, two and more than two hours had satisfaction scores of 0.93, 0.88 and 1.32 points higher on a ten-point scale (p < 0.03). CONCLUSIONS: Access to medical services is a concern for this population. Patients were dissatisfied with the waiting time for their first specialist appointment and with decreased access to allied health professionals. Patients travelling longer distances were more satisfied with their health care provider's care, suggesting that good patient-care giver relationships helped to ameliorate the difficulties of travelling to their appointments. Copyright © 2016 John Wiley & Sons, Ltd.
27616145 Validity and sensitivity to change of the semi-quantitative OMERACT ultrasound scoring sys 2016 Dec OBJECTIVES: The aim was to evaluate the metric properties of the semi-quantitative OMERACT US scoring system vs a novel quantitative US scoring system for tenosynovitis, by testing its intra- and inter-reader reliability, sensitivity to change and comparison with clinical tenosynovitis scoring in a 6-month follow-up study. METHODS: US and clinical assessments of the tendon sheaths of the clinically most affected hand and foot were performed at baseline, 3 and 6 months in 51 patients with RA. Tenosynovitis was assessed using the semi-quantitative scoring system (0-3) proposed by the OMERACT US group and a new quantitative US evaluation (0-100). A sum for US grey scale (GS), colour Doppler (CD) and pixel index (PI), respectively, was calculated for each patient. In 20 patients, intra- and inter-observer agreement was established between two independent investigators. A binary clinical tenosynovitis score was performed, calculating a sum score per patient. RESULTS: The intra- and inter-observer agreements for US tenosynovitis assessments were very good at baseline and for change for GS and CD, but less good for PI. The smallest detectable change was 0.97 for GS, 0.93 for CD and 30.1 for PI. The sensitivity to change from month 0 to 6 was high for GS and CD, and slightly higher than for clinical tenosynovitis score and PI. CONCLUSION: This study demonstrated an excellent intra- and inter-reader agreement between two investigators for the OMERACT US scoring system for tenosynovitis and a high ability to detect changes over time. Quantitative assessment by PI did not add further information.
25530448 Evidence of ERBB3 gene association with rheumatoid arthritis predisposition. 2016 Feb AIM: ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3) gene was reported to be related with susceptibility to several autoimmune diseases. Taking this into account, we searched, for the first time, the ERBB3 gene association with rheumatoid arthritis liability. METHODS: One hundred and eighty-six RA patients and 147 controls were enrolled in the study. Polymerase chain reaction - restriction fragment length polymorphism assay was conducted in rs2271189 and rs2292239 genotyping. RESULTS: A statistically significant difference was observed in rs2271189 allele distribution between RA patients and controls (P = 0.029, odds ratio: 1.460, 95% confidence interval: 1.040-2.050). CONCLUSION: As far as we know, this is the first study which correlates ERBB3 gene with RA susceptibility, adding to a previous report of chromosome 12q13 association with RA liability. Furthermore, we confirmed that polymorphism rs2271189 can predict better ERBB3 gene association with disorders than the previously reported ERBB3 variants. More studies in other ethnic groups of patients are needed so as to reveal the extent of the herein observed genetic association.
27274008 HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Di 2016 Nov OBJECTIVE: Rheumatoid arthritis (RA) susceptibility HLA-DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes. METHODS: We tested the association of RA susceptibility HLA-DRB1 amino acids with the C-reactive protein (CRP) level, the tender joint count (TJC), the swollen joint count (SJC), the Disease Activity Score in 28 joints (DAS28), and the Health Assessment Questionnaire (HAQ) score in the Norfolk Arthritis Register (NOAR) and Early Rheumatoid Arthritis Study (ERAS) cohorts. Longitudinal modeling of disease activity/outcomes was performed using generalized linear latent and mixed models. Mediation analysis was performed using directed acyclic graphs to investigate the paths from genetic factors to outcome. RESULTS: A total of 2,158 patients were available for analysis in the NOAR cohort. Valine at position 11 showed the strongest association with the CRP level (P = 2.21 × 10(-6) ), the SJC (P = 7.51 × 10(-6) ), and the DAS28 (P = 0.002); it was marginally associated with the HAQ score (P = 0.044) but not with the TJC. The same amino acid and haplotype risk hierarchy observed for susceptibility and radiographic severity was observed for the CRP level and nonradiographic measures of disease activity/outcome, apart from the TJC. The results were replicated in the ERAS cohort. The effect of valine at position 11 on the SJC was mainly mediated by anti-citrullinated protein antibody status, the effect of which was mainly mediated by inflammation; however, the effect of valine at position 11 was also independent of the CRP level (P = 1.6 × 10(-4) ). CONCLUSION: Genetic markers of RA susceptibility located within HLA-DRB1 determine the levels of clinical and systemic inflammation independently, and also determine all objective measures of disease activity and outcome.
25512473 Facilitators and barriers to adherence in the initiation phase of Disease-modifying Antirh 2015 Mar OBJECTIVE: To explore themes associated with adherence in the initiation phase for first-time use of disease-modifying antirheumatic drugs (DMARD) in patients with inflammatory arthritis using focus groups and individual interviews. METHODS: Thirty-three patients were interviewed in focus groups and individual interviews. Interviews were transcribed verbatim and imported into ATLAS.ti software (Scientific Software Development GmbH). Responses that included reasons for adherence or nonadherence in the initiation phase were extracted and coded by 2 coders separately. The 2 coders conferred until consensus on the codes was achieved. Codes were classified into overarching themes. RESULTS: Five themes emerged: (1) symptom severity, (2) experiences with medication, (3) perceptions about medication and the illness, (4) information about medication, and (5) communication style and trust in the rheumatologist. CONCLUSION: Perceptions about medication and the communication style with, and trust in, the rheumatologist were mentioned the most in relation to starting DMARD. The rheumatologist plays a crucial role in influencing adherence behavior by addressing perceptions about medication, providing information, and establishing trust in the treatment plan.
26051628 Targeting inflammation in the prevention of cardiovascular disease in patients with inflam 2016 Jan Patients with inflammatory arthritis have increased risk of cardiovascular diseases (CVDs) compared with the general population. Subclinical carotid atherosclerosis and increased arterial stiffness are also common in these patients, which may serve as surrogate end points for cardiovascular (CV) events in clinical trials. Although exact mechanisms are still unclear, persistent systemic inflammation in patients with inflammatory arthritis may contribute to the development of CVD. Dysregulated innate immunity pathways in these patients may also play a role in accelerating atherosclerosis. During the last decade, effective suppression of inflammation by biological disease-modifying antirheumatic drugs has improved the disease outcome dramatically in patients with inflammatory arthritis. Growing evidence suggests that antitumor necrosis factor (TNF) therapy may prevent CVD in patients with rheumatoid arthritis. Nonetheless, data on non-TNF biologics are limited. Whether anti-TNF therapy may prevent CVD in patients with spondyloarthritis also remained unclear. In this review, we summarized the effect of both anti-TNF and non-TNF biologics on the CV system, including traditional CVD risk factors, endothelial function, arterial stiffness, subclinical atherosclerosis, and clinical CVD in patients with inflammatory arthritis.
25760279 Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other rheumatic 2015 May PURPOSE OF REVIEW: To provide an update on and the context of the recent findings obtained with novel statistical methods on the association of the human leukocyte antigen (HLA) locus with rheumatic diseases. RECENT FINDINGS: Novel single nucleotide polymorphism fine-mapping data obtained for the HLA locus have indicated the strongest association with amino acid positions 11 and 13 of HLA-DRB1 molecule for several rheumatic diseases. On the basis of these data, a dominant role for position 11/13 in driving the association with these diseases is proposed and the identification of causal variants in the HLA region in relation to disease susceptibility implicated. SUMMARY: The HLA class II locus is the most important risk factor for several rheumatic diseases. Recently, new statistical approaches have identified previously unrecognized amino acid positions in the HLA-DR molecule that associate with anticitrullinated protein antibody-negative and anticitrullinated protein antibody-positive rheumatoid arthritis. Likewise, similar findings have been made for other rheumatic conditions such as giant-cell arteritis and systemic lupus erythematosus. Interestingly, all these studies point toward an association with the same amino acid positions: amino acid positions 11 and 13 of the HLA-DR β chain. As both these positions influence peptide binding by HLA-DR and have been implicated in antigen presentation, the novel fine-mapping approach is proposed to map causal variants in the HLA region relevant to rheumatoid arthritis and several rheumatic diseases. If these interpretations are correct, they would direct the biological research aiming to address the explanation for the HLA-disease association. Here, we provide an overview of the recent findings and evidence from literature that, although relevant new insights have been obtained on HLA-disease associations, the interpretation of the biological role of these amino acids as causal variants explaining that such associations should be taken with caution.
25581770 Association of socioeconomic status with treatment delays, disease activity, joint damage, 2015 Jul OBJECTIVE: To examine the association of socioeconomic status (SES) and delays in disease-modifying antirheumatic drug (DMARD) treatment with clinical measures in rheumatoid arthritis (RA) patients. METHODS: RA patients were recruited from rheumatology practices. We assessed SES based on education, occupation, and income, and divided patients into tertiles. The time from RA symptom onset to DMARD initiation (DMARD lag) was determined by self-report of the 2 dates, and distance to the rheumatologist (Distance) was obtained from Google Maps. We examined disease activity, determined by the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR); joint damage, determined from hand radiographs by Sharp scores; and physical disability, determined by the modified Health Assessment Questionnaire (M-HAQ). We used linear regression models to examine the relationship between clinical measures and SES, Distance, and DMARD lag. RESULTS: We recruited 1,209 RA patients, 1,159 of whom had received DMARD treatment. Mean ± SD DMARD lag was 6.9 ± 9.0 years. On average, patients with lower SES waited 8.5 ± 10.2 years after onset of RA symptoms to begin DMARD treatment, compared to those in the middle and upper SES tertiles who waited 6.1 ± 7.9 years (P = 0.002) and 6.1 ± 8.6 years (P = 0.009), respectively. Each year of delayed treatment was associated with a DAS28-ESR increase of 0.02 (P ≤ 0.001), a Sharp score increase of 1.33 (P ≤ 0.001), and an M-HAQ score increase of 0.01 (P ≤ 0.001). CONCLUSION: Low SES was associated with delay in DMARD initiation, and both were independently associated with worse clinical measures in RA. Strategies to reduce treatment delay in low-SES RA patients are needed.
26700281 An algorithm to identify rheumatoid arthritis in primary care: a Clinical Practice Researc 2015 Dec 23 OBJECTIVE: Rheumatoid arthritis (RA) is a multisystem, inflammatory disorder associated with increased levels of morbidity and mortality. While much research into the condition is conducted in the secondary care setting, routinely collected primary care databases provide an important source of research data. This study aimed to update an algorithm to define RA that was previously developed and validated in the General Practice Research Database (GPRD). METHODS: The original algorithm consisted of two criteria. Individuals meeting at least one were considered to have RA. Criterion 1: ≥ 1 RA Read code and a disease modifying antirheumatic drug (DMARD) without an alternative indication. Criterion 2: ≥ 2 RA Read codes, with at least one 'strong' code and no alternative diagnoses. Lists of codes for consultations and prescriptions were obtained from the authors of the original algorithm where these were available, or compiled based on the original description and clinical knowledge. 4161 people with a first Read code for RA between 1 January 2010 and 31 December 2012 were selected from the Clinical Practice Research Datalink (CPRD, successor to the GPRD), and the criteria applied. RESULTS: Code lists were updated for the introduction of new Read codes and biological DMARDs. 3577/4161 (86%) of people met the updated algorithm for RA, compared to 61% in the original development study. 62.8% of people fulfilled both Criterion 1 and Criterion 2. CONCLUSIONS: Those wishing to define RA in the CPRD, should consider using this updated algorithm, rather than a single RA code, if they wish to identify only those who are most likely to have RA.