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ID PMID Title PublicationDate abstract
27908307 Evolution of imaging findings, laboratory and functional parameters in rheumatoid arthriti 2017 Jan OBJECTIVES: To investigate the efficacy and safety of anti-TNF-α agent treatment compared to non-biologic DMARDs in rheumatoid arthritis patients. METHODS: 82 consecutive patients, 29 males, 53 females, aged 42-79, diagnosed with RA and suitable for anti-TNF-α treatment composed two study groups: 42 with pre-existing rheumatoid arthritis-related interstitial lung disease (RA-ILD) and 40 without RA-ILD. Respective control groups consisted of 44 patients with pre-existing RA-ILD and 44 patients without RA-ILD, treated with non-biologic DMARDs. All patients underwent chest high resolution computed tomography (HRCT), pulmonary function tests (PFTs) and peripheral blood biomarkers at baseline and after one year of treatment. RESULTS: There was a significant decrease of air trapping extent and bronchial wall thickening after treatment in RA-ILD and RA-non ILD study groups (p<0.05). This was accompanied by a statistically significant improvement of maximum mid-expiratory flow (MMEF75-25), RV and RV/TLC in both study groups (p<0.05). In the RA-ILD study group ILD extent scores remained unchanged after anti-TNF-α treatment. None of the RA-non ILD group developed new-onset ILD. In both RA-ILD and RA-non ILD control groups, HRCT findings and PFTs did not differ significantly at the one-year follow-up study. Methotrexate (MTX) regression analysis showed in both RA-ILD study and control groups a negative correlation between MTX dose and ILD extent score at one-year and between MTX dose and air trapping extent at baseline and after one year of treatment. CONCLUSIONS: Anti-TNF-α treatment, in contrast to non-biologic DMARDs, there was an improvement of small airways disease. There was no new-onset ILD or exacerbation of preexisting-ILD, especially in patients treated with anti-TNF-α agents, supporting the efficacy and favourable safety profile of this treatment in RA patients.
28652209 Heightened autoantibody immune response to citrullinated calreticulin in bronchiectasis: I 2017 Aug Calreticulin (CRT) and citrullinated (citCRT) are implicated in rheumatoid arthritis (RA) pathology. citCRT binds to RA shared epitopes (SE) on HLA-DR molecules with high affinity and triggers pro-inflammatory events in adjacent cells. The aim of the study was to detect the presence of citCRT prior to developing RA and evaluate if citCT is a target for autoantibodies in RA cohorts with and without lung disease. Antibodies were assessed by ELISA against native CRT, citCRT and general protein citrullination, in sera from 50 RA patients without lung disease, 122 bronchiectasis (BR) patients, 52 bronchiectasis patients with RA (BRRA), 87 asthma patients and 77 healthy controls (HC). Serum citCRT was detected by immunoblotting and mass spectrometry. Genomic DNA was genotyped for HLA-DRB1 alleles. Patients were assessed for DAS28, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. Extracellular citCRT was detected in BR patients sera prior to them developing RA. A citCRT SE binding peptide GEWKPR(261cit)QIDNPDYK was identified. Anti-CRT antibodies were observed in 18% of BR patients with or without RA. Anti-citCRT antibodies were observed in ∼35% of BR or RA patients, increasing to 58% in BRRA patients. In the RA alone patients 7/20 (35%) who were negative for RF and anti-CCP were anti-CRT antibody positive and had higher DAS28 scores than triple negative RA alone patients. Three of the four BR patients who developed RA over 18 months were anti-citCRT+ve SE(+ve). The detection of citCRT in BR and development of anti-citCRT in BR patients suggests citCRT antigens are early targets of antigenicity in these patients, especially in SE(+ve) patients prior to the onset of RA.
28277784 Association Between MTHFR C677T Polymorphism and Methotrexate Treatment Outcome in Rheumat 2017 May PURPOSE: Methotrexate (MTX) is one of the most widely used disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA). However, its efficacy in RA patients is variable and unpredictable. Methylene tetrahydrofolate reductase (MTHFR) is an important enzyme in the MTX pathway and is involved in folate metabolism and DNA synthesis. Several studies have examined the association between the MTHFR C677T polymorphism and MTX toxicity and efficacy in RA, but their conclusions remain controversial. MATERIALS AND METHODS: We conducted a comprehensive literature search of the PubMed, Embase, and Cochrane Library databases to identify studies reporting an association between the MTHFR C677T single nucleotide polymorphism and MTX response in RA patients. RESULTS: We identified 16 studies reporting MTX efficacy in 2373 RA cases, and 25 studies reporting MTX toxicity in 4063 RA cases. The pooled data analysis indicated that the MTHFR C677T polymorphism was associated with increased toxicity, but not efficacy, of MTX in RA patients. Further stratification based on ethnicity revealed an association between the MTHFR 677TT genotype and overall MTX toxicity in East Asian and Caucasian patient populations. In addition, RA patients with the MTHFR C677T polymorphism who were supplemented with folic acid displayed significantly elevated risk for MTX toxicity. CONCLUSION: Our study indicated that the MTHFR C677T polymorphism could be used as a predictor of MTX toxicity in RA patients. However, large randomized prospective studies will be required to effectively replicate and validate these findings.
28850582 Comparison of the effects of forefoot joint-preserving arthroplasty and resection-replacem 2017 PURPOSE: The purpose of this retrospective study is to clarify the difference in plantar pressure distribution during walking and related patient-based outcomes between forefoot joint-preserving arthroplasty and resection-replacement arthroplasty in patients with rheumatoid arthritis (RA). METHODS: Four groups of patients were recruited. Group1 included 22 feet of 11 healthy controls (age 48.6 years), Group2 included 36 feet of 28 RA patients with deformed non-operated feet (age 64.8 years, Disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.3), Group3 included 27 feet of 20 RA patients with metatarsal head resection-replacement arthroplasty (age 60.7 years, post-operative duration 5.6 years, DAS28-CRP 2.4), and Group4 included 34 feet of 29 RA patients with metatarsophalangeal (MTP) joint-preserving arthroplasty (age 64.6 years, post-operative duration 3.2 years, DAS28-CRP 2.3). Patients were cross-sectionally examined by F-SCAN II to evaluate walking plantar pressure, and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty joint-preserving arthroplasty feet were longitudinally examined at both pre- and post-operation. RESULTS: In the 1st MTP joint, Group4 showed higher pressure distribution (13.7%) than Group2 (8.0%) and Group3 (6.7%) (P<0.001). In the 2nd-3rd MTP joint, Group4 showed lower pressure distribution (9.0%) than Group2 (14.5%) (P<0.001) and Group3 (11.5%) (P<0.05). On longitudinal analysis, Group4 showed increased 1st MTP joint pressure (8.5% vs. 14.7%; P<0.001) and decreased 2nd-3rd MTP joint pressure (15.2% vs. 10.7%; P<0.01) distribution. In the SAFE-Q subscale scores, Group4 showed higher scores than Group3 in pain and pain-related scores (84.1 vs. 71.7; P<0.01) and in shoe-related scores (62.5 vs. 43.1; P<0.01). CONCLUSIONS: Joint-preserving arthroplasty resulted in higher 1st MTP joint and lower 2nd-3rd MTP joint pressures than resection-replacement arthroplasty, which were associated with better patient-based outcomes.
29069487 NF-κB1/IKKε Gene Expression and Clinical Activity in Patients With Rheumatoid Arthritis. 2017 Dec 22 OBJECTIVE: Rheumatoid arthritis (RA) is a systemic and autoimmune disorder whose primary characteristic is the chronic inflammation of joints. The objective of this study was to evaluate whether there was an association between nuclear factor kappa beta1/IKK epsilon (NF-κB1/IKKε) gene expression and clinical activity in RA. METHODS: Sixty patients with RA were included in the study: 30 with clinical activity and 30 with clinical remission. NF-κB1/IKKε gene expression was performed by real-time quantitative polymerase chain reaction through relative quantification with Taqman probes. A ROC curve for NF-κB1 and IKKε was also constructed. RESULTS: There were significant differences in NF-κB1 and IKKε gene expression (P ≤ .001 and P ≤ .029, respectively) between RA patients with clinical activity and clinical remission. The multivariate lineal general model showed that the use of nonsteroidal anti-inflammatory drugs influenced the NF-κB1 (P = .046) and IKKε (P = .005) expression. The ROC curves for the event "clinical activity" showed the greater area under the curve for NF-κB1 (0.827, 95% CI 0.717-0.937), P ≤ .001. CONCLUSION: Although the use of NSAIDs influences the NF-κB1/IKKε pathway, the IKKε expression might be a useful laboratorial analysis to evaluate the RA clinical activity.
27936459 MiR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting IKKα 2017 Feb The inflammatory cytokine interleukin 17 (IL-17) is an important contributor of rheumatoid arthritis (RA) chronicity. Although several microRNAs (miRNAs) have been shown to regulate RA pathogenesis, the function of miRNAs in articular chondrocytes during rheumatoid arthritis pathogenesis is unclear. Here we showed that miR-23a was downregulated in articular cartilage tissues from rheumatoid arthritis patients. MiR-23a suppressed IL-17 inflammatory cytokine-induced NF-κB activation and several proinflammatory mediators expression, such as cytokine IL-6, chemokine MCP-1, and matrix metalloproteinase MMP-3 in articular chondrocytes. Furthermore, we found that the miR-23a expression was inversely correlated with IKKα expression in articular cartilage tissues from rheumatoid arthritis patients. We identified that IKKα was the direct target of miR-23a and miR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting the IKKα in primary articular chondrocytes. Together, our study provides the first evidence of a role for miR-23a regulated IL-17-mediated proinflammatory mediators expression in rheumatoid arthritis by directly targeting IKKα. Our findings provide novel evidence that may be useful for future studies exploring therapeutic approaches for rheumatoid arthritis by targeting miR-23a. Thus, miR-23a may be a common therapeutic target for rheumatoid arthritis.
27589926 Radiographic changes and factors associated with subsequent progression of damage in weigh 2017 Jul OBJECTIVES: The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. METHODS: Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. RESULTS: Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p < 0.001, OR:24.85, 95%CI: 5.07-121.79) and disease activity at one year after treatment (p = 0.003, OR:3.34, 95%CI:1.50-7.46) as independent factors associated with the progression of joint damage. On the other hand, multivariate analysis for distal weight-bearing joints identified disease activity at one year after treatment (p < 0.001, OR:2.13, 95%CI:1.43-3.18) as an independent factor related to the progression of damage. CONCLUSIONS: Baseline Larsen grade was strongly associated with the progression of damage in the proximal weight-bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.
28845495 A novel ultrasound-based technique to establish a correlation between disease activity and 2017 May 10 AIM: Cardiovascular (CV) disease is the reason for most mortality cases in RA and cannot be explained only by the presence of traditional CV risk factors. In this study, we aimed to investigate the relationship between local carotid stiffness (CS) parameters measured by a novel ultrasound method and inflammatory disease activity in rheumatoid arthritis (RA) patients. Material and methods: The study was conducted with 70 RA patients and 35 control subjects. According to their disease activity score (DAS-28), the RA patients were classified into active RA (n = 36; DAS-28 > 3.2) and inactive RA (n = 34; DAS-28 ≤ 3.2) groups. A novel non-invasive echo-tracking system was used to measure carotid intima-media thickness (C-IMT), diameter, pulsatile strain, distensibility, and carotid pulse wave velocity (PWV) on 128 sites of the common carotid artery. Erythrocytesedimentation rate (ESR) and C-reactive protein (CRP) levels were also determined. RESULTS: Carotid PWV and IMT were significantly higher in the active RA patients (8.20±1.47 m/s and 6.88±1.50 mm, respectively) compared to the inactive group (6.06±1.21 mm and 7.32±1.19 m/s, respectively) and the control subjects (0.68±0.12 mm and 6.41±0.98, respectively). In all RA patients, a statistically significant correlation was found between carotid PWV and age (r=0.435, p<0.001), ESR (r=0.257, p=0.033), and DAS-28 (r=0.314, p=0.009). According to the multivariate logistic regression analysis, age, DAS-28, and ESR were independent predictors of CS. CONCLUSION: A strong correlation was found between disease activity and local CS parameters in patients with RA. We also demonstrated that both active and inactive RA patients showed increased PWV values compared with the control subjects. This easily applicable and previously confirmed method can be used in future to assess cardiovascular risk in broad study populations from different risk groups.
28516887 Tenosynovitis in rheumatoid arthritis patients on biologic treatment: involvement and sens 2017 Nov OBJECTIVES: Extensor carpi ulnaris (ECU) and tibialis posterior (TP) tendons are often involved in RA and the present aim was to examine by ultrasound (US) their frequency of inflammation and sensitivity to change in comparison to joint involvement as well as clinical examinations. METHODS: US, clinical and laboratory assessments were performed when starting biologic DMARD (bDMARD) and after 1, 2, 3, 6 and 12 months including bilateral grey-scale (GS) and power Doppler (PD) semi-quantitatively (0-3) scoring of ECU and TP tendons and 18 joints. Changes from baseline to follow-up were explored by Wilcoxon signed rank test, associations by Spearman's rank correlations and responses to treatment by Standardised Response Means (SRMs). RESULTS: 157 patients (mean age/disease duration 52.4/10.2 years) were included. ECU/TP tenosynovitis was frequent (baseline GS/PD pathology in 76/50% of patients) and more prevalent than synovitis of large joints. Tenosynovitis sum scores decreased throughout follow-up (p<0.001) and was correlated with US of joints (0.51-0.62), clinical assessments (swollen joint count (0.29-0.41) and assessor's global (0.35-0.46)) (p<0.001). US tenosynovitis sum scores had SRMs comparable to joint, clinical and laboratory assessments. CONCLUSIONS: Tenosynovitis in ECU/TP tendons were frequent, sensitive to change during bDMARD treatment and were associated to joint and clinical assessments. This supports the argument for tenosynovitis to be included in US scores of RA patients, while further studies should explore which tendons.
28817201 Exposure-Response Modeling and Power Analysis of Components of ACR Response Criteria in Rh 2017 Sep Population pharmacokinetic/pharmacodynamic (PK/PD) models were developed to quantitate the exposure-response relationships using continuous longitudinal data on American College of Rheumatology (ACR) subcomponents, that is, tender-joint count (TJC), swollen-joint count (SJC), C-reactive protein, patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, and patient's assessment of physical function for 5 biologics approved for use in rheumatoid arthritis. The models were then used to simulate the time courses of clinical outcomes following different treatment regimens. The relative sensitivity of the 7 subcomponents was assessed using Monte Carlo simulation-based power analysis. The developed population PK/PD models adequately described the relationship between serum concentrations and changes in ACR subcomponents. The trial simulation and subsequent power analysis showed that SJC and TJC appeared to be more sensitive than the other 5 ACR subcomponents to detect treatment effect over placebo/methotrexate. These 7 ACR subcomponents had similar power in detecting the treatment difference between different doses. In addition, the continuous measures of ACR subcomponents did not appear to be more sensitive than binary measures.
28199724 Cardiovascular risk management in rheumatoid arthritis patients still suboptimal: the Impl 2017 Sep 1 OBJECTIVE: To assess the 10-year cardiovascular (CV) risk score and to identify treatment and undertreatment of CV risk factors in patients with established RA. METHODS: Demographics, CV risk factors and prevalence of cardiovascular disease (CVD) were assessed by questionnaire. To calculate the 10-year CV risk score according to the Dutch CV risk management guideline, systolic blood pressure was measured and cholesterol levels were determined from fasting blood samples. Patients were categorized into four groups: indication for treatment but not treated; inadequately treated, so not meeting goals (systolic blood pressure ⩽140 mmHg and/or low-density lipoprotein ⩽2.5 mmol/l); adequately treated; or no treatment necessary. RESULTS: A total of 720 consecutive RA patients were included, 375 from Reade and 345 from the Antonius Hospital. The mean age of patients was 59 years (s.d. 12) and 73% were female. Seventeen per cent of the patients had a low 10-year CV risk (<10%), 21% had an intermediate risk (10-19%), 53% a high risk (⩾20%) and 9% had CVD. In total, 69% had an indication for preventive treatment (cholesterol-lowering or antihypertensive drugs). Of those, 42% received inadequate treatment and 40% received no treatment at all. CONCLUSION: Optimal CV risk management remains a major challenge and better awareness and management are urgently needed to reduce the high risk of CVD in the RA population.
29096558 Expression of aryl hydrocarbon receptor, inflammatory cytokines, and incidence of rheumato 2017 Dec Many Vietnamese citizens have been and continue to be inadvertently exposed to dioxins and dioxin-like compounds deposited in the country during the Vietnam War. Dioxins may be involved in the pathogenesis of inflammatory diseases in part via by affecting expression of aryl hydrocarbon receptor (Ahr) and inflammatory cytokines in animal models. As the role of the Ahr in dioxin-exposed people is not well defined, a study was conducted to examine gene expression levels of Ahr, inflammatory cytokines, and the incidence of diseases in dioxin-exposed citizens who had/still resided near a heavily dioxin-contaminated area in Vietnam. Whole blood from citizens at/around Da Nang airbase and control individuals living in unsprayed areas was collected. Serum levels of dioxins were analyzed by using a dioxins-responsive chemical-activated luciferase gene expression bioassay. Gene expression of Ahr, interleukin (IL)-1β, TNFα, IL-6, and IL-22 in whole blood was examined by quantitative real-time PCR. The results showed levels of dioxins and expression of Ahr, IL-1β, TNFα, and IL-6 were up-regulated while IL-22 expression was down-regulated in dioxin-exposed people. Various disease incidences in the study subjects was also examined. Interestingly, the incidence of rheumatoid arthritis (RA) in these individuals was increased compared to the estimated prevalence of this disease in the general Vietnamese population. Analyses also showed that expression levels of Ahr correlated to those of IL-6 and IL-22 in the dioxin-exposed people. Taken together, dioxins might be involved in an up-regulated expression of Ahr that might possibly relate to changes in level of inflammatory cytokines and, ultimately, in the incidence of select diseases in residents of Vietnam who had/continue to live near a dioxins-contaminated site.
27132481 Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional anal 2017 May INTRODUCTION: In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. METHODS: A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. RESULTS: The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. CONCLUSION: Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors.
28641552 A Review of the Psychometric Properties and Use of the Rheumatoid Arthritis Quality of Lif 2017 BACKGROUND: Several Patient-Reported Outcome Measures (PROMs) have been used in studies of Rheumatoid Arthritis (RA). Most of these assess Health-Related Quality of Life (HRQL). The exception is the Rheumatoid Arthritis Quality of Life questionnaire (RAQoL). This scale measures the impact of RA and its treatment from the patient's perspective, making it suitable for determining the value patients gain from interventions. OBJECTIVE: This review collates literature reporting on the efficacy of the RAQoL as a measure of patient value in clinical studies. METHOD: A literature search was conducted to identify published articles reporting on the use of the RAQoL. Psychometric and clinical research studies were included in the review. RESULTS: Sixty-three full articles were identified. Psychometric analyses demonstrated that the RAQoL meets the requirements for internal consistency, reproducibility and construct validity. There is evidence to support the unidimensionality and responsiveness of the RAQoL. The measure has been used in a wide range of research studies including interventional, correlational and nonexperimental studies. Several studies found the RAQoL to be sensitive to change following interventions. CONCLUSION: The RAQoL has excellent psychometric properties and can detect the impact of both clinical and non-clinical interventions. As a patient-centric measure of patient value, the RAQoL will also prove valuable in big data analytics and for use in outcomes-based reimbursement (OBR).
28255643 Use of etanercept to treat rheumatoid arthritis in an HIV-positive patient: a case-based r 2017 Jul Rheumatoid arthritis (RA) is a relatively common autoimmune disease that is associated with progressive disability and systemic complications, with a relatively high socioeconomic burden. The treatment of RA has been revolutionized by the use of biological drugs, such as anti-tumor necrosis factor (TNF) agents. A wide spectrum of RA disease severity has been reported among patients with human immunodeficiency virus (HIV) infection. Yet, only a few cases using anti-TNF therapy have been described in this clinical population. Therefore, the aim of our case-based review was to describe the successful use of etanercept in a 38-year-old female patient with RA concomitant with HIV infection, who had been resistant to the first-line anti-rheumatic therapies. As per routine care guidelines, the patient was screened for hepatitis virus infection, latent tuberculosis, and other infectious conditions, prior to the initiation of etanercept treatment. CD4 cell count, HIV viral load, and adverse effects were closely monitored during the treatment. The HIV infection remained stable with etanercept treatment, without the need for anti-retrovirus agents. No adverse effects and serious infections were identified during the treatment. Therefore, anti-TNF therapy is a viable alternative for the treatment of RA in patients with HIV, who do not respond to conventional anti-rheumatic therapies. The relationship between TNF-α and HIV infection, as well as cautionary guidelines regarding the utilization of anti-TNF therapy in this clinical population, is discussed.
26878896 Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biolog 2017 Mar PURPOSE: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents. METHODS: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer's II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed. RESULTS: Thirty-eight patients with a mean age of 53.00 ± 8.19 years were in group 1 and 18 patients with a mean age of 51.00 ± 9.54 years were in group 2. The mean duration of RA was 6.89 ± 7.96 years in group 1 and 5.70 ± 9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer's II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05). CONCLUSIONS: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower.
27704183 Autoimmune arthritis deteriorates bone quantity and quality of periarticular bone in a mou 2017 Feb This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.
27390149 Incidence of Chronic Persistent Rheumatoid Arthritis and the Impact of Smoking: A Historic 2017 May OBJECTIVE: To assess the incidence of chronic persistent rheumatoid arthritis (RA) in a population-based cohort of twins and to determine the impact of smoking. METHODS: In a historical cohort study on twins born in 1920 to 1982, we identified 157 cases of RA among 45,280 responders (response rate 80%). Information on smoking was obtained by questionnaire and interview. A mixed-effects Poisson regression model was used to estimate incidence rate ratios with age, sex, smoking duration, and smoking intensity as covariates. We used the SplitLexis procedure in the Epi R package to study a possible effect of period or cohort in addition to age on the variation of the incidence. RESULTS: The annual incidence of chronic persistent RA was 18.8 per 100,000 person-years, ages 15-73 years (females 25.2, males 12.0), increasing with age to a maximum at age 60 years in females and age 70 years in males. The incidence rate ratio among ever-smoking patients was 1.96 (95% confidence interval [95% CI] 1.43-3.76), 1.93 (95% CI 1.00-3.7) after 30 pack-years, and 1.034 (P < 0.001) per year of smoking, implying a doubling of risk after 20 years regardless of sex and smoking intensity. We did not detect significant period or cohort effects. CONCLUSION: The incidence of chronic persistent RA is lower than the incidence figures reported in inception cohorts. Smoking duration, but not intensity, doubled the risk of RA after 20 years of smoking in both sexes.
28138340 The experience of foot problems and decisions to access foot care in patients with rheumat 2017 BACKGROUND: Although foot problems are common in rheumatoid arthritis (RA), the consequences of foot problems from the patient perspective have not been fully explored. The aims of this study were to explore the experience of foot problems and decisions to access foot care services or not in patients with RA. METHODS: Semi structured, one-to-one interviews with patients recruited from 2 UK rheumatology units, purposively sampled for self-reported foot problems and a range of personal/disease characteristics. Inductive thematic analysis was used, with rigour provided by multiple independent analysers. Emerging themes were discussed and agreed by all authors. RESULTS: Twelve patients participated: 7 female; mean age 56 years (29-72); mean disease duration 12 years (2-27), 5 had accessed foot care services. The 'Impact' of foot problems was substantial and formed the underpinning theme, comprising three organising themes: 'Foot symptoms'; 'Consequences'; and 'Cost'. Foot symptoms such as pain and numbness required self-management, and affected daily life (walking, working) leading to social and emotional costs. The global theme, 'Decision to access foot care or not', also comprised three organising themes: 'Access perceived unnecessary' (no problem, can cope); 'Access hindered by patients' perception'; and 'Access supported by patient and clinician'. Decisions to access foot care or not were complex and influenced by patient beliefs regarding possible treatments and how to access these, and hindered by patient perceptions that their feet were ignored by rheumatology clinicians. Positive experience of foot care encouraged continued utilisation but negative experiences contributed to patients' decisions to discontinue foot care services. CONCLUSIONS: Foot problems are important issues for patients and impact on many aspects of their physical, social and emotional lives. Patients who had accessed foot care services prioritised their foot problems as an important health care need. However, for others who would like foot care services, personal knowledge and values, and perceived barriers in clinical practice, appear to interact to inhibit foot care access. The extent which these interactions affect overall access to foot care in RA patients in general now needs to be quantified to help to inform and improve the effectiveness of the organisation and delivery of foot care.
29143933 Long-term effectiveness of tocilizumab in patients with rheumatoid arthritis, stratified b 2018 Apr In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naïve patients and those with previous failures of biologic disease-modifying antirheumatic drugs (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or ≥ 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naïve patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with ≥ 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with ≥ 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with ≤ 2 bDMARD failures but significantly lower in those with ≥ 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures.