Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27478294 A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology. 2016 Matrix metalloproteinases are a class of enzymes involved in the degradation of extracellular matrix molecules. While these molecules are exceptionally effective mediators of physiological tissue remodeling, as occurs in wound healing and during embryonic development, pathological upregulation has been implicated in many disease processes. As effectors and indicators of pathological states, matrix metalloproteinases are excellent candidates in the diagnosis and assessment of these diseases. The purpose of this review is to discuss matrix metalloproteinases as they pertain to cartilage health, both under physiological circumstances and in the instances of osteoarthritis and rheumatoid arthritis, and to discuss their utility as biomarkers in instances of the latter.
28216540 Effectiveness of exercise-induced cytokines in alleviating arthritis symptoms in arthritis 2016 Recently, health awareness in Japan has been increasing and active exercise is now recommended to prevent lifestyle-related diseases. Cytokine activities have many positive effects in maintaining the health of a number of organs in the body. Myokines are cytokines secreted by skeletal muscles in response to exercise stimulation, and have recently generated much attention. Around 700,000 patients in Japan suffer from rheumatoid arthritis, making it the most prevalent autoimmune disease that requires active prevention and treatment. In the present study, a mouse model of spontaneous arthritis (SKG/Jcl) was subjected to continuous exercise stimulation, starting before the disease onset, to examine the effects of anti-inflammatory and inflammatory cytokine secretion on arthritis. For this stimulation, we developed a device that combines shaking and vibration. The results revealed that exercise stimulation delayed the onset of arthritis and slowed its progression. Thickened articular cartilage and multiple aggregates of chondrocytes were also observed. Further, exercise stimulation increased the expression of IL-6, IL-10, and IL-15, and inhibited TNF-α expression. From these results, we infer that the anti-inflammatory effects of IL-6 and IL-10, which showed increased expression upon exercise stimulation, inhibited the inflammatory activity of TNF-α and possibly delayed the onset of arthritis and slowed its progression. Novel methods for preventing and treating arthritis under clinical settings can be developed on the basis of these findings.
26125675 Regression of an atlantoaxial rheumatoid pannus following posterior instrumented fusion. 2015 Oct OBJECTIVE: Rheumatoid patients may develop a retrodental lesion (atlantoaxial rheumatoid pannus) that may cause cervical instability and/or neurological compromise. The objective is to characterize clinical and radiographic outcomes after posterior instrumented fusion for atlantoaxial rheumatoid pannus. METHODS: We retrospectively reviewed all patients who underwent posterior fusions for an atlantoaxial rheumatoid pannus at a single institution. Both preoperative and postoperative imaging was available for all patients. Anterior or circumferential operations, non-atlantoaxial panni, or prior C1-C2 operations were excluded. Primary outcome measures included Nurick score, Ranawat score (neurologic status in patients with rheumatoid arthritis), pannus regression, and reoperation. Pannus volume was determined with axial and sagittal views on both preoperative and postoperative radiological images. RESULTS: Thirty patients surgically managed for an atlantoaxial rheumatoid pannus were followed for a mean of 24.43 months. Nine patients underwent posterior instrumented fusion alone, while 21 patients underwent posterior decompression and instrumented fusion. Following a posterior instrumented fusion in all 30 patients, the pannus statistically significantly regressed by 44.44%, from a mean volume of 1.26cm(3) to 0.70cm(3) (p<0.001), over 8.02 months. The Nurick score significantly improved from 2.40 to 0.60 (p<0.001), but the marginal improvement of 0.20 in the Ranawat score did not reach significance (p=0.312). Six patients (20%) required reoperations over a mean of 13.18 months. Reoperations were indicated for C1 instrumentation failure in four patients and pseudoarthrosis in two patients. CONCLUSION: Following posterior instrumented fusion, the pannus radiographically regressed by 44.44% over a mean of 8.02 months, and patients clinically improved per the Nurick score. The Ranawat score did not improve, and 20% of patients required reoperation over a mean of 13.18 months. The annualized reoperation rate was approximately 13.62%.
26628599 Is Disease Activity in Rheumatoid Arthritis during Pregnancy and after Delivery Predictive 2016 Jan OBJECTIVE: To determine whether disease activity in women with rheumatoid arthritis (RA) in 1 pregnancy is predictive for disease activity in a subsequent pregnancy. METHODS: In the Pregnancy-induced Amelioration of Rheumatoid Arthritis study, there are prospective data on 27 patients who participated twice. Improvement and deterioration is determined by changes in the Disease Activity Score in 28 joints. RESULTS: Only 4 patients (14.8%) had comparable disease courses in both pregnancies, whereas treatment remained mostly similar. In contrast, a flare postpartum after the first pregnancy was predictive for a flare after the second pregnancy (p = 0.003). CONCLUSION: RA disease course in following pregnancies cannot be predicted based upon previous pregnancies. However, a flare postpartum seems to predict subsequent flares.
27782866 Increased mortality of incident rheumatoid arthritis versus matched non-RA control subject 2017 Mar OBJECTIVES: This study aimed to critically investigate all-cause and major-cause mortality of incident rheumatoid arthritis (RA) cases versus matched non-RA comparison (CN) subjects in a long-term prospective cohort. METHODS: Baseline 1974 cohort entry demographic and serum biomarker data on 54 incident RA patients and 216 matched CN subjects were related to their mortality from 1995 through 2015. Mortality of RA patients was also analysed by 3 categories of course responses to therapy assigned by the sole community rheumatologist in 1995 (19 good, 23 fair, and 12 limited). Cox proportional hazards regression models including baseline covariates were used to determine survival from all-causes, cardiovascular disease (CVD), respiratory-related, malignancies, and other causes of death (CODs). RESULTS: Total deaths occurred in 38 (70.4 percent) of 54 RA and 102 (47.7 percent) of 216 CN (p=0.003). Total mortality remained greater (p=0.011) in RA versus CN subjects after adjustment for baseline demographic covariates (HR= 1.66, 95% CI 1.12-2.46). Respiratory-related CODs were also greater (p=0.047) in RA versus CN (HR= 2.69, 95% CI 1.02-7.14) subjects. The RA patients' responses to therapy in 1995 significantly (p=0.004) predicted total mortality. Baseline serum immunological and steroid biomarkers independently predicted total, CVD, and other and unknown CODs. Pre-clinical (1974) ranked biomarker z-score values (1 = lowest, 5 = highest) within matched sets of 1 RA and 4 CN study subjects independently associated with mortality from 1995 through 2015, for both total (CRP, p=0.028 and sIL-2Rα, p=0.030) and CVD (CRP, p=0.005 and sTNF-R1, p=0.003) deaths. CONCLUSIONS: Total mortality and respiratory-related CODs were greater in incident RA versus CN subjects. The 35 RA cases who had fair or limited course responses to rheumatologist's therapy had greater mortality than their matched CN, whereas the 19 good RA responders had equivalent survival to CN subjects. The independent CRP and sTNF-R1 biomarker associations with CVD deaths were enhanced by a gradient of their dichotomous z-score values in survival models.
26057192 The role of autoreactive T cell in the pathogenesis of rheumatoid arthritis and implicatio 2015 Jun Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic inflammation of joint synovial tissue and subsequent destruction of associated bone, cartilage and soft tissues. RA is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs), traditional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids and biologic inhibitors of TNF, IL-1, IL-6, T cells and B cells. The use of these drugs especially biological agents has greatly improved the treatment of RA. Although the pathogenesis of RA remains unclear, T-cell mediated immune response is considered as a critical contributor in RA initiation and progression. It has been hypothesized that arthritogenic T cells (autoreactive T cells) escaping negative selection can recognize arthritogenic antigens and lead to autoimmunity and tissue destruction. Due to the important role of autoreactive T cells in the mechanisms of RA, they might be a novel therapeutic target. Many vaccines targeting autoreactive T cells which can establish immunological self tolerance have been developed. The efficacy of these vaccines has been justified in experimental models of RA and clinical trials. Inhibition of autoreactive T cell response by vaccination might provide a new treatment opinion in RA.
25504261 Inflammation, adiposity, and atherogenic dyslipidemia in rheumatoid arthritis: is there a 2015 Feb Dyslipidemia is highly prevalent in rheumatoid arthritis (RA) and appears to be present very early in the RA disease process, in some studies even before a diagnosis of clinical RA has been made. The association between lipid measures and the risk of cardiovascular disease (CVD) in RA appears to be paradoxical, whereby lower levels of total cholesterol (TC), low-density lipoprotein (LDL-C), and atherogenic ratios are associated with higher CVD risk. This may be due to the lipid-lowering effects of RA-related systemic inflammation. Therefore, standard CVD risk calculators have been shown to underperform in RA. Data also suggest that lipoprotein particle sizes and the apolipoprotein cargo of lipoproteins skew toward atherogenic dyslipidemia in RA and may contribute to the initiation and progression of atherosclerosis. Inflammatory burden in RA may also alter the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol (HDL-C). Adipose tissue is quantitatively increased in RA patients compared with matched non-RA controls and may be more inflamed and metabolically dysfunctional compared with an otherwise similar non-RA patient. In vitro, animal, and a handful of non-RA human, studies suggest that inflamed, metabolically dysfunctional adipose tissue contributes directly to lower HDL-C levels. In turn, lower HDL-C that has been altered functionally by inflammation may lead to expanded adipose mass and further adipose dysfunction and inflammation. In the last part of this review, we speculate how the RA disease state may recapitulate these processes.
27269296 Disease activity is associated with reduced left ventricular systolic myocardial function 2017 Feb OBJECTIVES: Disease activity has emerged as a new, independent risk factor for cardiovascular disease in patients with rheumatoid arthritis (RA). We tested if disease activity in RA was associated with lower left ventricular (LV) systolic function independent of traditional cardiovascular risk factors. METHODS: Echocardiographic assessment was performed in 78 patients with RA having low, moderate or high disease activity (Simplified Disease Activity Index (SDAI) >3.3), 41 patients in remission (SDAI ≤3.3) and 46 controls, all without known cardiac disease. LV systolic function was assessed by biplane Simpson ejection fraction, stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS). RESULTS: Patients with active RA had higher prevalence of hypertension and diabetes compared with patients in remission and controls (both p<0.05). LV ejection fraction (endocardial function) was normal in all three groups, while mean scMWS and GLS (myocardial function) were reduced in patients with RA with active disease compared with patients with RA in remission (95±18% vs 105±17% and -18.9±3.1% vs -20.6±3.5%, respectively, both p<0.01). Patients with RA in remission had similar scMWS and GLS as the controls. In multivariable analyses, having active RA was associated with lower GLS (β=0.21) and scMWS (β=-0.22, both p<0.05), both reflecting lower LV systolic myocardial function, independent of cardiovascular risk factors and LV ejection fraction. Classification of RA disease activity by other disease activity composite scores yielded similar results. CONCLUSIONS: Active RA is associated with lower LV systolic myocardial function despite normal ejection fraction and independent of traditional cardiovascular risk factors.
26354025 Efficacy of etanercept for treating the active rheumatoid arthritis: an updated meta-analy 2016 Nov AIM: To evaluate the efficacy of etanercept (ETA) for treating active rheumatoid arthritis (RA) compared to placebo or methotrexate (MTX). METHODS: We searched Medline, Cochrane Library and Wiley databases. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare efficacy. RESULTS: In total, 12 studies with 3878 active RA patients (including 2046 patients treated with ETA and 1832 patients treated with placebo or MTX) were included. The overall RRs in ACR20, 50 and 70 (20%, 50%, 70% improvement based on the criteria of American Rheumatism Association) were 2.10 (95% CI: 1.45-3.02, P < 0.0001), 2.87 (95% CI: 1.66-4.97, P = 0.0002) and 2.16 (95% CI: 1.49-3.13, P < 0.0001) within 24 weeks, respectively and were 1.19 (95% CI: 1.11-1.28, P < 0.00001), 1.37 (95% CI: 1.22-1.53, P < 0.00001) and 1.57 (95% CI: 1.28-1.92, P < 0.00001) within 1-3 years, respectively. Further, the overall RRs of 25 mg versus 10 mg ETA twice weekly in ACR20, 50 and 70 were 1.10 (95% CI: 1.02-1.19, P < 0.02), 1.37 (95% CI: 0.98-1.92, P < 0.07) and 1.27 (95% CI: 1.02-1.58, P < 0.03), respectively. CONCLUSIONS: In active RA patients treated with ETA, there was significantly higher efficacy compared to the treatment of placebo or MTX. High doses of ETA were more effective for active RA patients.
25469793 Association of polymorphisms in interleukin (IL)-12A and -B genes with rheumatoid arthriti 2015 Apr Rheumatoid arthritis (RA) is characterized by synovial infiltrates and progressive cell-mediated destruction of the joints, which results in significant disability and early mortality. Genetic factors may play an important role in the development of RA. The aim of this study was to investigate the association of common polymorphisms in interleukin (IL)-12A and IL-12B genes with RA in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in IL-12 genes were genotyped in 412 patients with RA and 279 control subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our data showed that IL-12B gene SNPs rs3212227 and rs6887695 were observed as a risk factor of RA. The minor allele (C) frequency of IL-12B gene rs3212227 and rs6887695 increased the risk of RA. Individuals carrying the rs3212227/rs6887695 C/C haplotype were associated with a significantly increased risk of RA. RA patients with the C allele of IL-12B gene rs6887695 was a protective factor to erosive arthropathy. Carriers of the C allele of IL-12B gene rs3212227 were significantly more likely to be RF-positive. No significant association was observed between rs2243115 in IL-12A and RA, due probably to the limited power. These results suggest that common variants in IL-12B may contribute to the development of RA in the Chinese population.
28121526 For Autoimmune Ills, Biologics Bring Promise-And Problems. 2016 Jul The development of recombinant DNA and other technologies has added a new dimension to care. These medications have revolutionized the treatment of rheumatoid arthritis and many of the other 80 or so autoimmune diseases. But they can be budget busters and have a tricky side effect profile.
26253105 Knowledge-based analysis of genetic associations of rheumatoid arthritis to inform studies 2015 Aug 8 INTRODUCTION: Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. Gene variants directly affect the normal processes of a series of physiological and biochemical reactions, and therefore cause a variety of diseases traits to be changed accordingly. Moreover, a shared genetic susceptibility mechanism may exist between different diseases. Therefore, shared genes, with pleiotropic effects, are important to understand the sharing pathogenesis and hence the mechanisms underlying comorbidity. METHODS: In this study, we proposed combining genome-wide association studies (GWAS) and public knowledge databases to search for potential pleiotropic genes associated with rheumatoid arthritis (RA) and eight other related diseases. Here, a GWAS-based network analysis is used to recognize risk genes significantly associated with RA. These RA risk genes are re-extracted as potential pleiotropic genes if they have been proved to be susceptible genes for at least one of eight other diseases in the OMIM or PubMed databases. RESULTS: In total, we extracted 116 potential functional pleiotropic genes for RA and eight other diseases, including five hub pleiotropic genes, BTNL2, HLA-DRA, NOTCH4, TNXB, and C6orf10, where BTNL2, NOTCH4, and C6orf10 are novel pleiotropic genes identified by our analysis. CONCLUSIONS: This study demonstrates that pleiotropy is a common property of genes associated with disease traits. Our results ascertained the shared genetic risk profiles that predisposed individuals to RA and other diseases, which could have implications for identification of molecular targets for drug development, and classification of diseases.
25648633 IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by polyarthritis. Numerous agents with varying mechanisms are used in the treatment of RA, including non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and some biological agents. Studies to uncover the cause of RA have recently ended up scrutinizing the importance of pro-inflammatory cytokine such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the pathogenesis of RA. TNF-α inhibitors are increasingly used to treat RA patients who are non-responsive to conventional anti-arthritis drugs. Despite its effectiveness in a large patient population, up to two thirds of RA patients are found to be partially responsive to anti-TNF therapy. Therefore, agents targeting IL-6 such as tocilizumab (TCZ) attracted significant attention as a promising agent in RA treatment. In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers including sarilumab, ALX-0061, sirukumab, MEDI5117, clazakizumab, and olokizumab, and their future perspectives in the treatment of RA.
25982887 Developing a Tailored Smoking Cessation Intervention for Rheumatoid Arthritis Patients. 2016 Mar PURPOSE: Smoking is associated with an increased risk of comorbidities in rheumatoid arthritis (RA) and may reduce the efficacy of anti-rheumatic therapies. Smoking cessation is therefore an important goal in RA. Our previous qualitative research identified five RA-related barriers to smoking cessation: lack of support; limited knowledge of the relationship between smoking and RA; uncontrolled pain; inability to exercise; and using smoking as a coping strategy. The aim of this article is to describe the process of developing a smoking cessation intervention for RA patients based on these themes. METHODS: A comprehensive review of the literature on smoking cessation was undertaken. A tailored smoking cessation programme was designed to address each RA-specific barrier. A meeting was convened with key staff of Arthritis New Zealand to develop a consensus on feasible design to deliver a smoking cessation programme based on existing best practice and smoking cessation resources, and tailored within existing Arthritis New Zealand service delivery frameworks. RESULTS: A three-month intervention was designed to be delivered by trained arthritis educators, with the following key components: nicotine replacement therapy for eight weeks; a telephone or face-to-face interview with each patient to determine their individual specific RA-related barriers to smoking cessation; and individualized education and support activities which addressed these barriers. The intervention also included three follow-up telephone calls; a support website; and 12 weekly smoking cessation advice emails. CONCLUSIONS: A RA-specific smoking cessation invention was developed, matching support to specific issues within each patient's experience. A pilot study is in progress to evaluate the programme's efficacy. Copyright © 2015 John Wiley & Sons, Ltd.
26697768 Pregnancy and rheumatoid arthritis. 2015 Aug Fertility is impaired in female patients with rheumatoid arthritis (RA), which is related to disease activity and the use of certain medication. During pregnancy, disease activity usually improves, but less than previously thought. Especially in women with high disease activity, the pregnancy outcome is also impaired. All of this underscores the importance of strict control of disease activity in RA patients who wish to conceive. Management of RA disease activity during pregnancy might be a challenge as the treatment options are limited. Evidence is accumulating that tumor necrosis factor (TNF) blockers can be safely used during pregnancy, particularly during the first trimester and the beginning of the second trimester. Far less is known about the problems faced by male RA patients who wish to conceive, in terms of not only fertility and pregnancy outcome but also the safety of medication. In this paper, the fertility issues in patients with RA, the pregnancy-associated improvement of RA, the pregnancy outcomes, including the long-term effects on the offspring, and treatment options, including those during lactation and for male patients wishing to conceive, will be reviewed.
27926913 Effect of rheumatoid arthritis on strength, dexterity, coordination and functional status 2016 Oct OBJECTIVE: To evaluate the effect of rheumatoid arthritis (RA) on strength, dexterity, coordination and functional status of the hand and to determine the relation with magnetic resonance imaging (MRI) findings. MATERIALS AND METHODS: Thirty eight patients with RA and thirty three controls were included in the study. There were five drop-outs in RA group. Pain was assessed by visual analog scale. Painful and swollen joints of the dominant hand were recorded. Hand deformities of the patients were noted. Hand grip strength and pinch strength of the dominant hand were evaluated. Hand disability was assessed by Duruoz hand index (DHI) and the Purdue pegboard test was used for assessment of coordination and dexterity. MRI of the dominant wrist and hand was performed in RA group. MRI scans were evaluated for synovitis, tenosynovitis, bone erosion and bone edema. RESULTS: Demographic characteristics were similar between groups. While DHI scores were significantly higher (p=0.000), Purdue pegboard test scores were significantly lower in RA group in comparison to control group (p=0.000). Bone edema and synovitis scores were significantly higher in patients with longer disease duration (p=0.025, p=0,006 respectively). There were significant negative correlation between grip strength, pinch strength subgroups and tenosynovitis scores (p=0.001, p=0,001). When the Purdue pegboard scores were lower, tenosynovitis scores were significantly higher (p=0.019, p=0,013, p=0,043). There was a significant positive correlation between DHI score and tenosynovitis score (p=0.003). CONCLUSION: This study showed that RA has significant negative impact on hand function and dexterity and the parameters used in the evaluation of hand function are mainly associated with tenosynovitis scores. Since tenosynovitis is a common pathology in RA, MRI can be used as a supportive method in early diagnosis of tenosynovitis and may be useful in identification of patients requiring aggressive treatment.
26729950 Outcome of rheumatoid arthritis following adjunct statin therapy. 2015 Nov OBJECTIVE: Rheumatoid arthritis (RA) is characterized by symmetric peripheral polyarthritis, inflammatory synovitis, and articular destruction. Statins, 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors, mediate significant vascular risk reduction in patients with coronary artery disease by promoting reduction in plasma levels of low-density-lipoprotein cholesterol. Extensive in vitro data, experimental studies and more recently few clinical trials have strongly suggested statins to possess an important role in RA mainly mediated by their anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the effect of adjunct statin therapy in comparison to standard disease modifying antirheumatic drugs (DMARD) therapy in patients with RA. MATERIALS AND METHODS: In this observational study, diagnosed RA patients of age group between 40 and 60 years were selected as per the inclusion criteria from the rheumatology outdoor. From the selected patients, we identified two separate groups of patients. Group 1 included 30 patients of RA currently under DMARD therapy with adjunct statin medication. Group 2 included 30 patients of RA currently under DMARD therapy. Patients were followed up over 6 months. Standard parameters such as disease activity score (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were recorded for comparing the outcome of RA in both groups. RESULTS: Out of a total of 60 patients who took part in the study, significant beneficial role of adjunct statin medication was found in this study when prescribed along with conventional DMARDs in active RA patients. The mean DAS28, considered by far as the most important index of clinical disease activity in RA, was found to be significantly lower (P < 0.05) in the adjunct statin-treated group (group 1) than that of the conventional DMARD treated group (group 2) after 6 months of continuous therapy. Other two important biochemical markers of RA disease activity, that is, ESR and CRP were also found to be significantly lower (P < 0.05) in RA patients who were on adjunct statin medication (group 1) than in group 2 comprising RA patients only under conventional DMARDs therapy without statin medication. CONCLUSION: The results suggest an adjunct and potentially beneficial role of statin therapy in active cases of RA, producing significant clinical and biochemical improvement.
26409609 Impact of Etanercept Therapy on Disease Activity and Health-Related Quality of Life in Mod 2015 Sep OBJECTIVES: To describe a population with moderate rheumatoid arthritis (RA) before biologic initiation and assess change in disease status, health-related quality of life (HRQOL), and adverse events in etanercept (ETN)-treated patients. METHODS: Data on adult patients with moderate RA (3.2 < Disease Activity Score in 28 Joints [DAS28] ≤ 5.1) were retrospectively analyzed from the British Society for Rheumatology Biologics Register comparing a nonbiologic-treated group (nBG) using at least one traditional disease-modifying antirheumatic drug to a biologic group (BG) treated with ETN. The HRQOL was assessed by using the Health Assessment Questionnaire disability index score. To mitigate confounding, we controlled for drivers of progression. Appropriate univariate, multivariate, and regression analyses were used. RESULTS: A total of 1754 patients with RA were assessed (211 BG and 1543 nBG). Compared with the nBG, the BG tended toward higher disease activity, such as significantly higher tender joints and DAS28. The BG compared with the nBG had 1) a greater reduction in DAS28 and Health Assessment Questionnaire scores; 2) disease remission occurring more often (odds ratio = 2.7; P = 0.006); and 3) progression occurring in fewer patients (odds ratio = 0.3; P = 0.002). BG patients had a higher incidence of "other serious infection" and "other central nervous system-related events," with no significant differences in associated hospitalization rates or deaths. CONCLUSIONS: Among patients with moderate RA from a clinical practice registry, ETN-treated patients had significantly higher disease activity at the time of biologic initiation but significantly reduced disease activity and better HRQOL after 6 months compared with nBG patients, although the possibility of unmeasured confounding remains. The ETN group reported significantly higher incidences of "other serious infections" and "other central nervous system-related events" without higher hospitalization rates.
26097059 Epidemiology and Treatment of New-Onset and Established Rheumatoid Arthritis in an Insured 2015 Dec OBJECTIVE: To investigate the epidemiology and treatment of rheumatoid arthritis (RA) in a population broadly representative of employed adults in the US, using a retrospective cohort design. METHODS: Incident and prevalent RA cohorts were defined from a sample of 4.66 million adults with complete followup data from the period of January 2005 through September 2008 in the Pharmetrics medical claims database. Demographics, comorbidity, and medical therapies were summarized using descriptive statistics. RESULTS: Median duration in the database was 5.7 years. Age- and sex-adjusted incidence in 2006 was 0.71 per 1,000 persons at risk (n = 3,992) and prevalence in 2005 was 0.63% (n = 30,530). Within 12 months after diagnosis, 65%, 64%, and 20% of the incident cohort had been prescribed corticosteroids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and tumor necrosis factor (TNF) inhibitors, respectively. Median time to first anti-TNF prescription was 6 months; 31% switched to a second drug and 15% to a third. An aggressive subcohort (11% of incident patients) received more DMARDs (83%) and TNF inhibitors (43%), and was more likely to switch. Twenty-eight percent of incident patients received only symptomatic therapy over a minimum of 1.75 years of followup; these patients were older with more comorbidities and contraindications to methotrexate. CONCLUSION: In this insured population-based cohort, only two-thirds of newly diagnosed RA patients were prescribed a DMARD in year 1 and 28% received no antirheumatic therapy. Although limited by lack of clinical information and by left-censoring, administrative databases capture clinical practice and suggest that gaps exist in treatment options available to a significant number of patients.
26247564 All-cause Mortality Associated with TNF-α Inhibitors in Rheumatoid Arthritis: A Meta-Anal 2015 Dec OBJECTIVE: To compare mortality data obtained from randomized controlled trials for the 5 tumor necrosis factor-α (TNF-α) inhibitors used in the treatment of rheumatoid arthritis. METHODS: A systematic review of articles published up to November 2014 was performed using electronic databases. We included randomized, controlled trials, with a follow-up period of at least 24 weeks, comparing TNF-α inhibitors to placebo or disease-modifying antirheumatic drugs. The primary outcome was the occurrence of all-cause mortality. RESULTS: Twenty-three studies were selected. These articles included 6525 patients in the anti-TNF-α group and 3523 in the control group. The duration of patient follow-up ranged from 24 to 104 weeks. The risk of all-cause mortality in patients receiving TNF-α inhibitors was not significantly different from those receiving the comparator (odds ratio 1.32; 95% confidence interval, 0.76-2.29). Subgroup analyses with respect to the molecule used, the dose received, the use of TNF-α inhibitors as monotherapy or combination therapy, or the quality of the trial did not modify the findings. CONCLUSION: This meta-analysis performed on a large number of patients and including the 5 TNF-α inhibitors currently available shows no increased risk of medium-term all-cause mortality in patients with rheumatoid arthritis.