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27015251 Impact of Out-of-Pocket Costs on Prescription Fills Among New Initiators of Biologic Thera 2016 Feb BACKGROUND: Biologic disease-modifying antirheumatic drug (DMARD) therapies are a mainstay of treatment for rheumatoid arthritis (RA), yet high member out-of-pocket (OOP) costs for such therapies may limit patient access to these therapies. OBJECTIVE: To understand whether there is a relationship between OOP costs and the initial fill and subsequent refills of biologic DMARD treatments for RA members. METHODS: Members of a national Medicare Advantage and Prescription Drug (MAPD) plan with an adjudicated (paid or reversed) claim for a biologic DMARD indicated for RA were identified from July 1, 2007, to December 31, 2012, and followed retrospectively. The first adjudicated claim date was the index date. Members were required to have 180 days of continuous enrollment pre- and post-index and ≥ 1 diagnosis for RA (ICD-9-CM: 714.0 or 714.2) during pre-index or ≤ 30 days post-index. Low-income subsidy and Medicaid-Medicare dual-eligible patients were excluded. The analysis used multivariate regression models to examine associations between initial prescription (Rx) abandonment rates and OOP costs and factors influencing the refill of a biologic DMARD therapy based on pharmacy claims. RESULTS: The final sample size included 864 MAPD members with an adjudicated claim for a biologic DMARD. The majority were female (77.4%) and mean age was 63.5 years (SD = 10.9). Most (78%) had conventional nonbiologic DMARD utilization during pre-index. The overall initial abandonment rate was 18.2% for biologic DMARDs, ranging from 1.3% for the lowest OOP cost group ($0-$250) to 32.7% for the highest OOP cost group (> $550; P < 0.0001 for Cochran-Armitage trend test). ORs for abandonment rose from 18.4 to 32.7 to 41.2 for OOP costs of $250.01-$400.00, $400.01-$550.00, and > $550.00 respectively, relative to OOP costs of ≤ $250.00 (all P < 0.0001). Meeting the catastrophic coverage limit and utilization of a specialty pharmacy for the index claim were both associated with a decreased likelihood of abandoning therapy (OR = 0.29 and OR = 0.14, respectively; both P < 0.05). Among the subset of 533 members with a paid claim, 82.4% had at least 1 refill post-index. The negative association between OOP cost and likelihood of refilling an Rx was highly significant (P < 0.0001). CONCLUSIONS: This study suggests that the higher the member OOP cost, the less likely an MAPD member is to initiate or refill a biologic DMARD therapy for RA. Further research is needed to understand reasons for initial Rx abandonment and lack of refills, including benefit design and adverse events.
26474615 [Risk factors for bone mineral density changes in patients with rheumatoid arthritis and f 2015 Oct 18 OBJECTIVE: To verify the fracture risk assessment tool (FRAX) to estimate the probability of osteoporotic fracture in patients with rheumatoid arthritis (RA) with or without bone mineral density (BMD), and identify associated risk factors of osteoporosis. METHODS: In the study, 200 patients with rheumatoid arthritis aged more than 40 years in Peking University First Hospital from Dec. 2009 to Dec. 2012 were recruited. Clinical information was obtained from a questionnaire of their case history and medical records. FRAX tool was administered. Their lumber spine and left femoral BMD were determined by dual energy X ray absorptiometry. The gender, age, disease duration, menopause status, body mass index (BMI) and accumulative dose of glucocorticoid were obtained in retrospect. Correlation analysis was conducted between the BMD and clinical information. RESULTS: The study population (female, 77.5%) had a mean age of 59.4 years, in which 10 (13%) patients showed a normal BMD, 67 (87%) were osteopenia or osteoporosis, while 32 patients (16%) had fragile fracture. Compared with the patients with normal BMD, the subjects with low BMD had significantly older age, longer period for corticoids usage, higher day dose and accumulated dose of corticoids.The 10-year fracture risk of sustaining major osteoporotic fractures and hip fracture was higher. No significant difference was observed between the 10-year fracture risks calculated with BMD and without BMD. The values of the different area under the receiver operating characteristic (ROC) curve (AUC) for major and hip fractures calculated in three ways: without BMD, with the femoral neck BMD, and with T-score. The best result was for FRAX tool for hip fracture with the T-score (AUC 0.899). A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low BMD. Three statistically significant variables for lumber BMD were pain on visual assessment scale (VAS) (P=0.02), fracture history (P=0.003) and a higher steroid accumulated dose (P=0.008). Three statistically significant variables for left hip BMD were age (P<0.001), fracture history (P=0.05) and lower BMI (P=0.03). CONCLUSION: Low BMD is a common complication in RA patients. Risk factors for major fracture and hip fracture are increased. There is a positive correlation between FRAX calculated with and without BMD or T score. FRAX with the femoral neck T score or BMD presents a discriminatory capacity better than FRAX without BMD, according to the AUC ROC.
27081759 TL1A increased IL-6 production on fibroblast-like synoviocytes by preferentially activatin 2016 Jul TNF-like protein 1A (TL1A), a member of tumor necrosis factor family, recognized as a ligand of death receptor 3 (DR3) and decoy receptor 3 (DcR3). The interaction of TL1A and DR3 may participate in the pathogenesis of some autoimmune diseases including rheumatoid arthritis (RA). Our previous results showed that high concentrations of TL1A could be found in synovial and serum in RA patients, and it was correlated with disease severity. In addition, TL1A could promote Th17 differentiation induced by TGF-β and IL-6 and increased the production of IL-17A. In the present study, we found that TL1A could promote the expression of IL-6 on fibroblast-like synoviocytes (FLS) of RA patients via NF-κB and JNK signaling pathway. TL1A-stimulated FLS increased the percentage of Th17 of peripheral blood mononuclear cells (PBMC) in RA via the production of IL-6, a critical cytokine involved in the differentiation of Th17. Moreover, the blocking of tumor necrosis factor receptor 2 (TNFR2) decreased TL1A-stimulated IL-6 production by RA FLS. Our results suggest that TL1A was capable of acting on RA FLS to elevate IL-6 expression, which promoted the production of Th17. More importantly, we showed that TL1A could influence RA FLS through binding to TNFR2 rather than DR3 on FLS, which indicated that the treatment of TNF inhibitors not only blocked the TNF but also suppressed the TL1A in RA patients.
27523470 Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate. 2017 Nov Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome.
26867862 Characteristics of resistin in rheumatoid arthritis angiogenesis. 2016 Jun Adipokines have been reported to be involved in the regulation of various physiological processes, including the immune response. Rheumatoid arthritis (RA) is an example of a systemic immune disease that causes chronic inflammation of the synovium and bone destruction in the joint. Recent therapeutic strategies based on the understanding of the role of cytokines and cellular mechanisms in RA have improved our understanding of angiogenesis. On the other hand, endogenous endothelial progenitor cells, which are a population isolated from peripheral blood monocytes have recently been identified as a homing target for pro-angiogeneic factor and vessel formation. In this review, we summarize the effects of common adipokines, such as adiponectin, leptin and resistin in RA pathogenesis and discuss other potential mechanisms of relevance for the therapeutic treatment of RA.
27534721 Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the r 2016 Aug 18 Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA.
25536122 Outcomes related to methotrexate dose and route of administration in patients with rheumat 2015 Mar OBJECTIVES: Methotrexate (MTX) is considered the 'anchor drug' in the therapy of rheumatoid arthritis (RA), yet many physicians do not optimise MTX regimens in spite of high RA disease activity. The recent development of an auto-injector for the subcutaneous (subQ) administration of MTX has prompted re-evaluation of MTX utilisation. The purpose of this systematic literature review is to determine the optimal dose, drug level, and route of administration for MTX in the context of relevant pharmacokinetics and pharmacogenomics. METHODS: A systematic literature review was performed in Medline searching specifically for randomised controlled trials, systematic reviews, case control and cohort studies evaluating outcomes related to MTX dose and route of administration. Articles fulfilling these inclusion criteria were reviewed. Data on MTX dose, route of administration, clinical response, drug levels and adverse events were evaluated. RESULTS: Our search identified 420 articles of which 6 were eligible for inclusion using the above criteria. These included 2 systematic reviews, 2 randomised open label trials, one longitudinal study and one retrospective cohort study. CONCLUSIONS: Efficacy and toxicity for MTX appear related to absorbed dose of MTX, not to route of administration. While bioavailability is greater for parenteral MTX, there is no evidence yet that splitting the oral dose of MTX is less advantageous, less safe or less tolerable than administering parenteral MTX. However, there appear to be modest benefits in beginning with higher doses of MTX, and switching to parenteral MTX when the clinical response to an oral dose is inadequate.
26822477 Depletion of regulatory T cells leads to an exacerbation of delayed-type hypersensitivity 2016 Apr Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregsand the role of IL-17 in connection with Tregdepletion. Given the relevance of Tregsin RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregsin inflammatory arthritis. Selective depletion of Tregswas achieved using aFoxp3-DTR-eGFPmouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of theFoxp3gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregsincreased in the paw and its draining lymph node in DTHA, and depletion of Tregsresulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Tregdepletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregsare important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using theFoxp3-DTR-eGFPmouse on a C57BL/6 background for Tregdepletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregsand IL-17 in arthritis.
27760092 Anxiety and depression levels in rheumatoid arthritis patients before and after joint repl 2016 Oct 19 The progression of the inflammatory process in the course of rheumatoid arthiritis (RA) may cause a permanent destruction of joints, which in case of bigger ones (i.e. hip or knee) may be particularly a psychological burden for a patient. AIM: The aim of the study was to verify whether implantation of hip or knee endoprosthesis affect anxiety and depressive symptoms among patients with RA. MATERIALS AND METHODS: The study enrolled a group of 128 rheumatoid arthritis patients, including 64 patients before and 64 patients after the joint replacement procedure. Anxiety was assessed using State- Trait Anxiety Inventory and depression - Beck Depression Inventory. RESULTS: Patients before the endoprosthesis implantation scored statistically significantly higher on the state anxiety scale than patients after the procedure (43.17±10.69 vs 36.95±10.63, p<0.01). There was no statistically significant difference in trait anxiety scores between patients before and after alloplasty (p=0.28). Patients before the procedure scored statistically significantly higher on BDI than patients after the joint replacement (15.28±8.99 vs 11.48±8.45, p<0.05). CONCLUSIONS: Patients with RA after knee or hip alloplasty had lower levels of anxiety and depressive symptoms than patient before the procedure. Endoprosthesis implantation as a treatment option for severe joint destruction in RA might also improve depressive symptoms and anxiety among patients with RA.
26110744 High-Frequency Ultrasound in the Evaluation of Psoriatic Arthritis: A Clinical Study. 2015 Jul BACKGROUND: This study aimed to compare high-frequency ultrasound (HFU) findings in the fingers with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and to explore the potential use of HFU in the early diagnosis of PsA. METHODS: Forty-four PsA patients with 123 fingers with symptoms, 39 RA patients with 122 fingers with symptoms and 20 healthy patients were recruited as controls. The ultrasound imaging manifestation and blood flow of fingers were recorded and compared. The results were analyzed by the χ test. RESULTS: Abnormal ultrasound findings in the fingers of RA and PsA patients were identified and compared. Among RA patients, 82 (67.21%) were diagnosed with joint effusion, 78 (63.93%) were synovial thickening and 59 (48.36%) were bone erosion, while no tenosynovitis, soft tissue inflammation or enthesitis was found. However, among the patients with PsA, 75 (60.97%) were diagnosed with joint effusion, 68 (55.28%) were synovial thickening, 71 (57.72%) were bone erosion, 71 (57.72%) were tenosynovitis, 44 (35.77%) were soft tissue inflammation and 39 (31.70%) were enthesitis. CONCLUSIONS: HFU proved valuable in detecting soft tissue inflammation and enthesitis in the fingers of PsA patients. HFU may be an easy, safe and effective examination in the early diagnosis of PsA and observation of pathological changes of PsA.
27682742 Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by compa 2017 Sep OBJECTIVES: To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059). METHOD: Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated. RESULTS: The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively. CONCLUSIONS: In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.
27014854 Specialty Tier-Level Cost Sharing and Biologic Agent Use in the Medicare Part D Initial Co 2016 Nov OBJECTIVE: To examine associations between specialty tier-level cost sharing and use of biologic agents for rheumatoid arthritis (RA) during Medicare Part D's initial coverage period (ICP). METHODS: This was a retrospective study using 2007-2010 5% sample Medicare files to examine RA patients with use of a Part D RA biologic agent in the prior year. Patients without low-income subsidies (non-LIS group), who faced specialty tier-level cost sharing, were compared to a control group of low-income subsidy patients (LIS group), who faced nominal out-of-pocket costs in the ICP. Outcomes included use of a Part D or Part B RA biologic agent during the ICP and presence of a ≥30-day continuous gap in treatment among Part D biologic agent users in the ICP. Risk-adjusted outcomes were estimated using logistic regressions, controlling for patient demographic, clinical, and Part D plan characteristics. RESULTS: On average, a 30-day Part D biologic agent supply cost the non-LIS group $484 out of pocket (29.9% cost sharing) versus $5 (0.3% cost sharing) for the LIS group. The non-LIS group was less likely to fill Part D biologic agents (61.2% versus 72.7%, odds ratio [OR] 0.58 [95% confidence interval (95% CI) 0.46-0.72]; P < 0.001), more than twice as likely to receive Part B biologic agents (9.9% versus 4.4%, OR 2.41 [95% CI 1.61-3.60]; P < 0.001), and less likely to use any biologic agent (70.1% versus 76.9%, OR 0.69 [95% CI 0.55-0.88]; P = 0.002). The non-LIS subgroup filling Part D biologic agents had approximately twice the odds of a gap in both Part D biologic agent and any biologic agent availability. CONCLUSION: Specialty tier-level cost sharing was associated with interruptions in RA biologic agent treatment among Medicare patients.
27799159 Patient-reported outcomes from a randomised phase III study of baricitinib in patients wit 2017 Apr OBJECTIVES: To assess baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis, who had insufficient response or intolerance to ≥1 tumour necrosis factor inhibitors (TNFis) or other biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: In this double-blind phase III study, patients were randomised to once-daily placebo or baricitinib 2 or 4 mg for 24 weeks. PROs included the Short Form-36, EuroQol 5-D, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, duration of morning joint stiffness (MJS) and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis. Treatment comparisons were performed with logistic regression for categorical measures or analysis of covariance for continuous variables. RESULTS: 527 patients were randomised (placebo, 176; baricitinib 2 mg, 174; baricitinib 4 mg, 177). Both baricitinib-treated groups showed statistically significant improvements versus placebo in most PROs. Improvements were generally more rapid and of greater magnitude for patients receiving baricitinib 4 mg than 2 mg and were maintained to week 24. At week 24, more baricitinib-treated patients versus placebo-treated patients reported normal physical functioning (HAQ-DI <0.5; p≤0.001), reductions in fatigue (FACIT-F ≥3.56; p≤0.05), improvements in PtGA (p≤0.001) and pain (p≤0.001) and reductions in duration of MJS (p<0.01). CONCLUSIONS: Baricitinib improved most PROs through 24 weeks compared with placebo in this study of treatment-refractory patients with previously inadequate responses to bDMARDs, including at least one TNFi. PRO results aligned with clinical efficacy data for baricitinib. TRIAL REGISTRATION NUMBER: NCT01721044; Results.
27787923 Age- and Sex-Dependent Changes of Intra-articular Cortical and Trabecular Bone Structure a 2017 Apr The objective of this cross-sectional study was to define normal sex- and age-dependent values of intra-articular bone mass and microstructures in the metacarpal heads of healthy individuals by high-resolution peripheral quantitative computed tomography (HR-pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra-articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR-pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra-articular (intracapsular) bone margins. These data were applied in measuring intra-articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra-articular and radial bone parameters were good (r = 0.51 to 0.62, p < 0.001). In contrast to radial bone, intra-articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm(3) ) but decreased significantly (p < 0.001) in women thereafter (237.5 ± 44.3) with loss of both cortical and trabecular bone. Similarly, RA patients showed significant (p < 0.001) loss of intra-articular total (263.0 ± 44.8), trabecular (171.2 ± 35.6), and cortical bone (610.2 ± 62.0) compared with sex- and age-adjusted controls. Standard sex- and age-dependent values for physiological intra-articular bone were defined. Postmenopausal state and RA led to significant decrease of intra-articular bone. © 2016 American Society for Bone and Mineral Research.
26814849 Differential Methylation as a Biomarker of Response to Etanercept in Patients With Rheumat 2016 Jun OBJECTIVE: Biologic drug therapies represent a huge advance in the treatment of rheumatoid arthritis (RA). However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority. We undertook this study to test our hypothesis that differential DNA methylation patterns may provide biomarkers predictive of response to tumor necrosis factor inhibitor (TNFi) therapy in patients with RA. METHODS: An epigenome-wide association study was performed on pretreatment whole blood DNA from patients with RA. Patients who displayed good response (n = 36) or no response (n = 36) to etanercept therapy at 3 months were selected. Differentially methylated positions were identified using linear regression. Variance of methylation at differentially methylated positions was assessed for correlation with cis-acting single-nucleotide polymorphisms (SNPs). A replication experiment for prioritized SNPs was performed in an independent cohort of 1,204 RA patients. RESULTS: Five positions that were differentially methylated between responder groups were identified, with a false discovery rate of <5%. The top 2 differentially methylated positions mapped to exon 7 of the LRPAP1 gene on chromosome 4 (cg04857395, P = 1.39 × 10(-8) and cg26401028, P = 1.69 × 10(-8) ). The A allele of the SNP rs3468 was correlated with higher levels of methylation for both of the top 2 differentially methylated positions (P = 2.63 × 10(-7) and P = 1.05 × 10(-6) , respectively). Furthermore, the A allele of rs3468 was correlated with European League Against Rheumatism nonresponse in the discovery cohort (P = 0.03; n = 56) and in the independent replication cohort (P = 0.003; n = 1,204). CONCLUSION: We identify DNA methylation as a potential biomarker of response to TNFi therapy, and we report the association between response and the LRPAP1 gene, which encodes a chaperone of low-density lipoprotein receptor-related protein 1. Additional replication experiments in independent sample collections are now needed.
27606890 Proprotein convertase subtilisin/kexin type 9 in rheumatoid arthritis. 2016 Nov OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors. CONCLUSIONS: PCSK9 is down-regulated in patients with RA.
26403284 Synthetic disease-modifying antirheumatic drug prescribing variability in rheumatoid arthr 2015 Nov The objective of this study was to describe the variability in the prescription of csDMARDs for the treatment of RA between centers in Spain and to explore how this variability relates to demographic, disease, physician, and institutional characteristics. A cross-sectional nationwide study was carried out to examine data from 1352 patients. Multilevel logistic regression with two levels was performed to assess the relationships between individual and disease-related factors, as well as physician and hospital characteristics, vis-à-vis csDMARD prescription. Having three or more comorbidities (OR 0.353 [0.173-0.721]), disease duration (OR 0.321 [0.174-0.595]), and the existence of an early-arthritis unit (OR 0.552 [0.335-0.910]) were negatively associated with the prescription of one csDMARD versus nonprescription; contrary, the presence of rheumatoid factor (OR 1.909, 95 % CI [1.181-3.086]) was positively associated. On the other hand, while corticoid intake (OR 1.561 [1.088-2.240]), the maximum number of painful joints, and the presence of nursing consultation (OR 1.626 [1.078-2.452]) were positively associated with the prescription of multiple csDMARDs versus one csDMARD, patient's age (OR 0.984 [0.974-0.995]) and disease duration (OR 0.669 [0.462-0.968]) were negatively associated. Despite all these, variability in the prescription of csDMARDs between hospitals remained statistically significant after adjusting for these individual and hospital characteristics. Within the emAR II study, there was a marked variation in the number of csDMARDs prescribed between hospitals. The reasons for these variations remain unclear and cannot be solely related to disease or center characteristics.
26239288 Evaluating Adherence to a Treat-to-Target Protocol in Recent-Onset Rheumatoid Arthritis: R 2016 Apr OBJECTIVE: To evaluate rheumatologists' adherence to a low Disease Activity Score (DAS)-steered treat-to-target (T2T) strategy in treatment of patients with rheumatoid arthritis (RA) and to assess associated conditions. METHODS: Data of the BeSt study were used, a multicenter T2T strategy trial with 10-year followup. During 3 monthly visits, the physician answered questions about satisfaction with level of RA suppression, agreement with the study protocol, and agreement with the DAS. Associations between the answers and nonadherence were evaluated. RESULTS: Protocol adherence decreased over time from 100% to 60% per visit, with an average over time of 79%. Rheumatologists mostly agreed with the DAS (80-90% of visits over time) and were satisfied with the treatment steps (75-90%) and with the level of RA suppression (85-90%). The odds for protocol violation were higher when the rheumatologist disagreed with the DAS (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 2.0-2.7 when they thought the DAS overestimated actual disease activity; OR 2.5, 95% CI 2.0-3.1 when they thought the DAS underestimated actual disease activity) or with the next required treatment step (OR 3.0, 95% CI 2.5-3.5), and when the physician was dissatisfied with disease suppression (OR 1.3, 95% CI 1.1-1.6). CONCLUSION: Rheumatologists generally agreed with and followed a 10-year followup DAS-steered T2T strategy. Disagreement with the DAS or the required treatment and dissatisfaction with the level of disease suppression were risk factors for nonadherence. These results indicate the feasibility of continued protocol-driven T2T therapy. For daily practice, adherence to T2T therapy might be improved by adopting the structure components of a clinical trial.
25342437 Does rheumatoid arthritis disease activity correlate with weather conditions? 2015 May To determine whether rheumatoid arthritis disease activity correlates with changing weather conditions. A longitudinal analysis of 133 patients attending the Department of Rheumatology, Musgrave Park Hospital, Belfast was performed. Participants had a diagnosis of rheumatoid arthritis and were receiving subcutaneous anti-TNF therapy (Adalimumab or Etanercept) for a period of >6 months. Data were collected at five time points. This included tender joint count, swollen joint count, patient visual analogue score (VAS), erythrocyte sedimentation rate, C-reactive protein, VAS, and DAS-28 (Disease Activity Score). Each weather factor (maximum, minimum temperature, pressure, rainfall, sunshine, humidity, and wind-speed) was analysed against each patients' DAS-28 score at five time points, using an analysis of covariance. A significant correlation was noted between low DAS-28 and increased hours of sunshine (p < 0.001). Sunny conditions were associated with a DAS-28 reduction of 0.037 (95 % CI -0.059, -0.016) p < 0.001. A significant correlation between humidity and DAS-28 was also noted (p = 0.016). Increased humidity was associated with an increased DAS-28 of 0.007 (95 % CI 0.001, 0.013) p = 0.016. Higher temperatures were associated with a non-significant decrease in DAS-28 (p = 0.16). In this study, rheumatoid arthritis disease activity (as measured by DAS-28) was significantly lower in both more sunny and less humid conditions.
24685909 Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis ser 2015 Aug OBJECTIVE: To develop and validate rheumatoid arthritis (RA) risk models based on family history, epidemiologic factors and known genetic risk factors. METHODS: We developed and validated models for RA based on known RA risk factors, among women in two cohorts: the Nurses' Health Study (NHS, 381 RA cases and 410 controls) and the Epidemiological Investigation of RA (EIRA, 1244 RA cases and 971 controls). Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in logistic regression models for the study population and for those with positive family history. The joint effect of family history with genetics, smoking and body mass index (BMI) was evaluated using logistic regression models to estimate ORs for RA. RESULTS: The complete model including family history, epidemiologic risk factors and genetics demonstrated AUCs of 0.74 for seropositive RA in NHS and 0.77 for anti-citrullinated protein antibody (ACPA)-positive RA in EIRA. Among women with positive family history, discrimination was excellent for complete models for seropositive RA in NHS (AUC 0.82) and ACPA-positive RA in EIRA (AUC 0.83). Positive family history, high genetic susceptibility, smoking and increased BMI had an OR of 21.73 for ACPA-positive RA. CONCLUSIONS: We developed models for seropositive and seronegative RA phenotypes based on family history, epidemiological and genetic factors. Among those with positive family history, models using epidemiologic and genetic factors were highly discriminatory for seropositive and seronegative RA. Assessing epidemiological and genetic factors among those with positive family history may identify individuals suitable for RA prevention strategies.