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

ID PMID Title PublicationDate abstract
25665185 Sonographic assessment of interstitial lung disease in patients with rheumatoid arthritis, 2015 Jul OBJECTIVES: The usefulness of transthoracic ultrasound in the evaluation of lung diseases has been highlighted in the past decades. The aim of our study is to determine the diagnostic value of lung ultrasound in the detection of interstitial pulmonary fibrosis in patients with a rheumatic disease. Furthermore, we studied the possible correlation between the underlying disease and the frequency of pathological ultrasound findings. METHODS: A sample of 45 consecutive patients with RA (n=25), SSc (n=14) and SLE (n=6) and 40 healthy volunteers were enrolled into the study. Every study patient underwent both, lung sonography and HRCT. The following ultrasound findings were documented in each study patient: B- lines, subpleural nodes and irregularities of the pleura. HRCT was analysed by an experienced radiologist blind to sonography findings. RESULTS: Twenty-eight percent of the RA cohort, 64% of the SSc patients and four out of 6 SLE patients showed ILD on HRCT. Pathological ultrasound patterns were significant more frequent in the ILD group than in the non-ILD group (comet tail artifacts/B-pattern: 100% vs. 12%, p<0.001; subpleural nodes: 55 % vs. 17%, p=0.006; thickenings of the pleural line: 95% vs. 12.5%, p<0.001). Subpleural nodes were present in 100% of the RA patients vs. 22% the SSc patients (p=0.003) and 50% of the SLE patients (p=0.049) with ILD. An irregular pleural line>3 mm was documented in 100% of SSC and SLE patients with ILD, vs. 86% of ILD patients suffering from RA (p=ns). CONCLUSIONS: Transthoracic ultrasound of the lung might be a sensitive non-invasive tool to observe early stage interstitial lung disease in rheumatic diseases.
27825791 Recommendations by the Spanish Society of Rheumatology for the management of patients diag 2017 May To establish a set of recommendations for the management of patients diagnosed with rheumatoid arthritis (RA) who cannot be treated with methotrexate (MTX) due to contraindications, drug toxicity or lack of adherence, and to establish therapeutic strategies more effective and safer in these RA patients. A qualitative analysis of the scientific evidence available to June 2015. The 2-round Delphi technique of consensus was used to collect and establish expert opinion based on the participants' clinical experience when only low quality evidence was available. A total of eighteen recommendations were developed for the management of this patient profile. Fourteen of these recommendations were related to drug safety aspects. Recommendations on contraindication and toxicity of MTX have been updated. The experts recommend the use of biological monotherapy, a preferred treatment option, in patients whose profiles reveal a contraindication, intolerance or circumstances that prevent us against the use of MTX. There is some high-quality scientific evidence that supports contraindication and establishes certain conditions of MTX use in RA patients with specific clinical profiles.
26064941 Osteoarticular Expression of Musashi-1 in an Experimental Model of Arthritis. 2015 BACKGROUND: Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating the maintenance and differentiation of stem/precursor cells. The objectives of this investigation were to perform a morphological study of the experimental CIA model, evaluate the effect of TNFα-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. METHODS: CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. RESULTS: Clinically, TNFα-blocker treatment attenuated CIA on day 32 after immunization (P < 0.001). Msi1 protein expression was significantly higher in joints damaged by CIA than in those with no lesions (P < 0.0001) and was related to the severity of the lesions (Spearman's rho = 0.775, P = 0.0001). CONCLUSIONS: Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair.
27338263 Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three 2016 Jun 23 BACKGROUND: METARTHROS (Metabolic impact on joint and bone disease) is a nationwide German network to investigate the overlap between inflammatory and metabolic diseases. The objective of this study was to compare the body mass index (BMI) distribution in patients with early and established rheumatoid arthritis (RA) with data from the general population, and to evaluate the association of BMI with patient characteristics and clinical markers. METHODS: The BMI distribution was examined with data collected at inclusion of patients in the early arthritis cohort CAPEA, the biologics register RABBIT, and the National database of the German Collaborative Arthritis Centers. A data source with a representative sample of the German population (German Ageing Survey) was used as a comparator. BMI categories of <18.5 kg/m(2) (underweight), 18.5 to <25 kg/m(2) (normal weight), 25 to <30 kg/m(2) (overweight), and ≥30 kg/m(2) (obese) were used. Patients were stratified by age and sex, and compared to controls from the German Ageing Survey. Associations between BMI and markers of disease activity were analysed with non-parametric tests and linear models. RESULTS: Data from 1207 (CAPEA), 12,230 (RABBIT), and 3424 (National database) RA patients and 6202 population controls were evaluated. The mean age was 56, 56, 62, and 62 years, respectively, the mean disease duration was 13 weeks, 9.9 years, and 13.5 years, respectively, and the mean disease activity score (DAS28) was 5.1, 5.2, and 3.1, respectively. In all RA cohorts, obesity was more frequent (23.8 %, 23.4 %, 21.4 %, respectively) than in controls (18.2 %). This applied to all age groups <70 years, was independent of disease duration, and was more pronounced in females. In all cohorts, the age at RA onset was associated with BMI, being higher in overweight/obese patients compared to normal-weight patients. Current smoking was negatively associated with BMI. Linear analyses revealed increased erythrocyte sedimentation rate (ESR) values in underweight and obese females, and an increasing disparity between tender joint counts (TJCs) and swollen joint counts (SJCs) in higher BMI categories. CONCLUSIONS: Compared to the general population, a higher prevalence of obesity was observed in all RA cohorts. The dominance of obesity in females and the different behaviour of disease activity markers in relation to the BMI in females indicate that additional parameters need to be considered when analysing the impact of obesity on inflammation in RA.
27133672 Thin-section chest CT findings in polymyalgia rheumatica: a comparison between with and wi 2016 May We retrospectively compared the thin-section chest computed tomography (CT) findings between 25 patients of polymyalgia rheumatica (PMR) with rheumatoid arthritis (RA) and 29 patients of PMR without RA. PMR patients showed high-frequency CT abnormalities (68.5%) regardless of the association with RA. Ground-glass opacity (56% vs. 24%), traction bronchiectasis (44% vs. 3%), architectural distortion (32% vs. 0%), centrilobular nodules (32% vs. 7%), and honeycombing (20% vs. 0%) were significantly more common in the PMR with RA group than in the PMR without RA group (P<.01). PMR patients with RA have more increased prevalence of chest CT abnormalities than those without RA.
25608046 Correlation between knee and hindfoot alignment in patients with rheumatoid arthritis: The 2015 Sep OBJECTIVES: Compensatory hindfoot alignment for deformities at the knee level has been demonstrated in patients with knee osteoarthritis. However, this phenomenon has not been elucidated in patients with rheumatoid arthritis (RA). The aim of this study is to investigate the relationship between knee deformity and hindfoot alignment and the effect of subtalar joint destruction in patients with RA. METHODS: We retrospectively investigated RA patients (110 patients, 205 limbs) using radiographs in the standing anteroposterior knee, standing lateral foot, and hindfoot alignment views. The grade of destruction at the knee and subtalar joints was assigned using Larsen's grading system. The correlation between the femorotibial and tibiocalcaneal angles and the effect of joint destruction on this correlation were analyzed using Pearson's correlation coefficients. RESULTS: There was moderate correlation between the femorotibial and tibiocalcaneal angles in a group of knees with a Larsen grade of ≥ 4 (r = 0.544, p = 0.0239). This correlation was stronger in a group with less damaged subtalar joints with a Larsen grade of ≤ 3 (r = 0.705, p = 0.0049). CONCLUSION: These findings emphasized the importance of examining foot and ankles in patients with RA who undergo total knee arthroplasty.
27932278 Patient-perceived flares in rheumatoid arthritis: A sub-analysis of the STRASS treatment t 2017 Oct OBJECTIVES: Patient's and physician's perspective can differ in rheumatoid arthritis (RA). The aim was to define the concept of patient-reported flares. METHODS: Post-hoc analysis of a randomized controlled trial of a step-down strategy in RA patients treated with anti-TNF, in DAS28-remission for ≥6 months, randomized to either "spacing" or "maintaining" anti-TNF. The occurrence of patient-reported flares (PRF) was evaluated every 3 months for 18 months by: "Over the last 3 months, did you experience symptoms suggestive of disease exacerbation?". Visits with and without PRF were compared, using a linear mixed effects model, in terms of symptoms, disability based on the Health Assessment Questionnaire, quality of life based on Short Form 36 Health Survey and DAS28-based relapses (DBR), defined as an increase of DAS28>0.6 and an absolute value of DAS28>2.6. The agreement between PRF and DBR was measured by the kappa coefficient on repeated data. RESULTS: In all, 137 patients were analyzed: mean age 55±11 years, females 78%, mean RA duration 9.5±8.0 years. Over the 18 months, PRF concerned 27.2% of the 940 available visits. DBR and PRF were observed in 24% and 16% of 940 visits for 137 patients respectively. All the items were associated with PRF with standardized effect size between -0.58 (SF36 PCS) and 0.87 (DAS28). The agreement between PRF and DBR was moderate (κ=0.44). CONCLUSION: The concept of flare refers to more than just RA disease activity.
27585685 Safety of Biologic Agents in Elderly Patients with Rheumatoid Arthritis. 2016 Nov OBJECTIVE: To clarify the safety of biologics in elderly patients with rheumatoid arthritis. METHODS: Biologics were analyzed for safety in relation to age in 309 patients. RESULTS: Young (< 65 yrs old, n = 174), elderly (65-74 yrs old, n = 86), and older elderly patients (≥ 75 yrs old, n = 49) were enrolled. Although the incidence of adverse events causing treatment withdrawal was significantly higher in elderly and old elderly compared with young patients, no difference was found between elderly and older elderly patients. Pulmonary complications were independent risk factors. CONCLUSION: Old patients require special attention, although the safety of biologics in those ≥ 75 years old and 65-74 was comparable.
27553386 Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study. 2016 Dec Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.
27707730 Discordance between tender and swollen joint count as well as patient's and evaluator's gl 2017 Apr OBJECTIVE: To investigate the predictive value of discordance between (1) tender and swollen joint count and (2) patient's and evaluator's global assessment on remission in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: From the prospective, multicentre Norwegian-Disease-Modifying Antirheumatic Drug study, we included patients with RA and PsA starting first-time tumour necrosis factor inhibitors and DMARD-naïve patients starting methotrexate between 2000 and 2012. The predictive value of ΔTSJ (tender minus swollen joint counts) and ΔPEG (patient's minus evaluator's global assessment) on remission was explored in prespecified logistic regression models adjusted for age, sex, disease duration and smoking. RESULTS: A total of 2735 patients with RA and 1236 patients with PsA were included (mean (SD) age 55.0 (13.5)/48.3 (12.4) years, median(range) disease duration 0.7 (0.0-58.0)/1.3 (0.0-48.3) years, 69.7/48.4% females). Baseline ΔTSJ/ΔPEG reduced the likelihood of achieving DAS28<2.6, SDAI≤3.3, CDAI≤2.8, ACR/EULAR Boolean and DAPSA<4 remission after 3 and 6 months in RA (OR 0.95-0.97, p<0.001/OR 0.96-0.99, p≤0.01) and PsA (OR 0.91-0.94, p≤0.004/OR 0.89-0.99, p≤0.002), except for ΔPEG and 6-month DAS28 remission in PsA. CONCLUSIONS: Discordance between patient's and physician's evaluation of disease activity reflected through ΔTSJ and partly ΔPEG may reduce likelihood of remission in RA and PsA. The findings are relevant for use of the treat-to-target strategy in individual patients.
26140464 Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patient 2016 OBJECTIVE: The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA). METHODS: The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17-87) years; median (range) disease duration, 8 (0.6-48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2-16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group). Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM. RESULTS: There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group. CONCLUSIONS: GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.
27157144 Telomere length, endothelial activation and carotid atherosclerosis in black and white Afr 2016 Sep OBJECTIVES: Our objective was to examine associations of traditional and non-traditional cardiovascular risk factors with relative leukocyte telomere length and confounder adjusted relationships of relative telomere length with endothelial activation and carotid atherosclerosis in black and white African patients with rheumatoid arthritis (RA). METHODS: Relative telomere length of leukocyte DNA in whole blood was determined using quantitative RT-PCR in 205 (101 black) African patients with RA. RESULTS: In demographic characteristic adjusted analysis, relative telomere length tended to be larger in black compared to white patients (median (IQR)=0.54 (0.42-0.54) and 0.48 (0.37-0.60) (p=0.07), respectively). In black patients, waist circumference, systolic, diastolic and mean blood pressure were associated with relative telomere length (β (SE)=-0.00270 (0.00114) (p=0.02), -0.00185 (0.00060) (p=0.003), -0.00243 (0.00112) (p=0.03) and -0.00225 (0.00075) (p=0.003), respectively); in white patients, age, anti-cyclic citrullinated antibody positivity, biologic agent use, a cholesterol-HDL cholesterol ratio of >4 and the number of major traditional risk factors were related to relative telomere length (β (SE) =-0.00242 (0.00113) (p=0.03), 0.06629 (0.03374) (p=0.05), -0.09321 (0.04310) (p=0.03), 0.08225 (0.03420) (p=0.02) and 0.04046 (0.01719) (p=0.02), respectively). One SD increase in relative telomere length was associated with carotid plaque (OR (95% CI)=1.65 (0.99-2.75) (p=0.05)) and vascular cell adhesion molecule-1 concentrations (β (SE)=-0.05031 (0.02480) (p=0.04)) in black and white patients, respectively. CONCLUSIONS: This study disclosed paradoxically direct relationships between relative telomere length and cardiovascular risk factors in white and atherosclerosis in black African RA patients. The role of relative telomere length in cardiovascular risk and its stratification in RA requires longitudinal investigation.
24458537 The effect of disease duration and disease activity on the risk of cardiovascular disease 2015 Jun OBJECTIVE: Disease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA. METHODS: RA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged  28 joint disease activity score (DAS28) for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were used for the analyses. RESULTS: During follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders. CONCLUSIONS: Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.
27914602 Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abat 2016 Nov A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.
27297801 Volume-normalized transfer constant as an imaging biomarker for chronic inflammatory arthr 2016 Sep PURPOSE: Proper diagnosis and treatment of rheumatoid arthritis are extremely important to optimize treatment outcomes. Dynamic contrast-enhanced MRI (DCE-MRI) may be used as a biomarker to detect inflammatory changes in synovial joints and to discriminate active and inactive stages of the disease. The aim of this study was to investigate vascular permeability changes associated with inflammatory arthritis progression and its treatment. METHODS: Arthritis was induced in DBA/1J mice by immunization with type-II collagen emulsified in complete Freund's adjuvant. Severity of arthritis was monitored using the clinical arthritis index. MR images of mice were obtained at different stages of arthritis progression and at 3 weeks after methotrexate treatment. Immunohistochemical staining using an anti-CD31 antibody was used to assess vessel density. RESULTS: Volume-normalized transfer constant increased progressively until the active stage of arthritis was reached, and thereafter declined gradually. The pattern of volume-normalized transfer constant changes quantified using DCE-MRI correlated with vascular densities and immunohistochemical findings. Furthermore, volume-normalized transfer constant and densities decreased significantly in a dose-dependent manner after treatment with methotrexate. CONCLUSION: Volume-normalized transfer constant assessed by DCE-MRI can be used as an imaging biomarker for tracking disease progression and for monitoring therapeutic efficacy in inflammatory arthritis. Magn Reson Med 76:926-934, 2016. © 2016 Wiley Periodicals, Inc.
25252152 KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates dise 2015 Jan OBJECTIVE: Fibroblast-like synoviocytes (FLS) participate in joint inflammation and damage in rheumatoid arthritis (RA) and its animal models. The purpose of this study was to define the importance of KCa1.1 (BK, Maxi-K, Slo1, KCNMA1) channel expression and function in FLS and to establish these channels as potential new targets for RA therapy. METHODS: We compared KCa1.1 expression levels in FLS from rats with pristane-induced arthritis (PIA) and in FLS from healthy rats. We then used ex vivo functional assays combined with small interfering RNA-induced knockdown, overexpression, and functional modulation of KCa1.1 in PIA FLS. Finally, we determined the effectiveness of modulating KCa1.1 in 2 rat models of RA, moderate PIA and severe collagen-induced arthritis (CIA). RESULTS: We found that PIA FLS expressed the KCa1.1 channel as their major potassium channel, as has been found in FLS from patients with RA. In contrast, FLS from healthy rats expressed fewer of these channels. Inhibiting the function or expression of KCa1.1 ex vivo reduced proliferation and invasive properties of, as well as protease production by, PIA FLS, whereas opening native KCa1.1 or overexpressing the channel enhanced the invasiveness of both FLS from rats with PIA and FLS from healthy rats. Treatment with a KCa1.1 channel blocker at the onset of clinical signs stopped disease progression in the PIA and CIA models, reduced joint and bone damage, and inhibited FLS invasiveness and proliferation. CONCLUSION: Our results demonstrate a critical role of KCa1.1 channels in the regulation of FLS invasiveness and suggest that KCa1.1 channels represent potential therapeutic targets in RA.
25205362 Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid fa 2015 OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity. RESULTS: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.
26869014 Effect of rituximab on pulmonary function in patients with rheumatoid arthritis. 2016 Apr BACKGROUND: Rituximab (RTX), a B-cell depleting monoclonal antibody is increasingly used in several antibody-mediated diseases. It has been reported to cause pulmonary toxicity, though mainly during polychemotherapy of malignant lymphoma. Prospective data on RTX-induced pulmonary complications in patients with rheumatoid arthritis (RA) are lacking. METHODS AND METHODS: Serial spirometries and measurements of diffusion capacity of the lung for carbon monoxide (DLCO) in patients with RA before and 2, 4, 8, and 26 weeks after treatment with RTX were performed. A reduction from baseline of forced vital capacity (FVC) of ≥10%, or ≥15% of DLCO was defined as indicative for pulmonary toxicity. RESULTS: Thirty-three patients (mean (SD) age 59 (12) years, 27% males) were included. Mean (SD) FVC predicted and DLCO predicted at baseline were 108% (18%) and 88% (18%), respectively. In contrast to FVC, DLCO showed a progressive decline during follow-up with a maximum reduction of 6.1% (95%CI 2.5%, 9.7%; p = 0.001) at 26 weeks compared with baseline. After 26 weeks, 22% of the patients had a ≥15% DLCO decline. None of the patients reported increased dyspnea during follow-up. Risk factors for pulmonary function changes after treatment with RTX were cigarette smoking, repeated administration of the drug, and co-medication with Prednisone. CONCLUSION: Although no cases of symptomatic lung injury were observed, the progressive DLCO decline seems to indicate the presence of subclinical RTX-induced pulmonary toxicity.
27692392 A new musculoskeletal ultrasound scoring system (US10) of the hands and wrist joints for e 2016 Sep OBJECTIVE: To propose a novel ultrasound scoring system for hand and wrist joints (US10) for evaluation of patients with early rheumatoid arthritis (RA) and to correlate the US10 with clinical, laboratory and functional variables. METHODS: Forty-eight early RA patients underwent clinical and laboratory evaluations as well as blinded ultrasound (US) examinations at baseline, three, six and 12 months. The proposed US10 system involved the assessment of the wrist, second and third metacarpophalangeal and proximal interphalangeal joints. The score consisted of inflammation parameters (synovial proliferation [SP], power Doppler [PD] and tenosynovitis [TN]) and joint damage parameters (bone erosion [BE] and cartilage damage [CD]). SP, PD, BE and CD were scored qualitatively (0-1) and semi-quantitatively (grades 0-3). Tenosynovitis was scored as presence/absence. The evaluation also involved the 28-Joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and C-reactive protein level (CRP). RESULTS: Mean duration of symptoms was 7.58±3.59 months. Significant correlations (p<0.05) were found between inflammation parameters and CRP at baseline and between the changes in these variables throughout the study. Significant correlations (p<0.05) were found between DAS28 score and both PD and TN at baseline and between the changes in DAS28 score and both SP and TN throughout the follow up. Moreover, significant correlations were found between the changes in inflammation parameter scores and HAQ score throughout the follow up. CONCLUSION: The proposed US10 scoring system proved to be a useful tool for monitoring inflammation and joint damage in early RA patients, demonstrating significant correlations with longitudinal changes in disease activity and functional status.
27344073 Associations between disease activity, markers of HDL functionality and arterial stiffness 2016 Aug BACKGROUND AND AIMS: Rheumatoid arthritis (RA) is a chronic, inflammatory disease associated with increased risk of cardiovascular disease (CVD). Measures of HDL metabolism/function were shown to be altered in RA patients with high disease activity. We aimed at evaluating the effect of HDL characteristics on arterial stiffness in RA patients classified according to the inflammatory disease activity. METHODS: RA patients were classified according to disease activity (DAS-28) into active RA (n = 27; DAS-28 > 3.2) and inactive RA patients (n = 17; DAS-28 < 3.2). A control group of healthy individuals was also studied (n = 33). Clinical and biochemical characteristics, cholesteryl ester transfer protein (CETP) and paraoxonase 1 (phenylacetate and paraoxonase) activities and carotid-femoral pulse wave velocity (cf-PWV) were determined. RESULTS: Anthropometric characteristics were similar in all groups. In accordance with the inflammatory status, active RA patients presented elevated hsCRP levels (p < 0.001). There were no differences in the lipid profile between groups. Similarly, features of insulin resistance were absent in RA patients (p = non-significant). Active RA patients presented higher CETP activity than the other two groups (p = 0.026). Phenylacetate and paraoxonase activities were altered in active RA patients in comparison with the other groups (p = 0.034 and p = 0.041, respectively). Cf-PWV was significantly higher in active RA patients in comparison with controls, following adjustment by age (p = 0.030). Age (βst = 0.468, p = 0.013) and apo A-I levels (βst = -0.405, p = 0.029) were independent predictors of cf-PWV in a model including hsCRP, HOMA-IR, and phenylacetate activity (r(2) = 0.42). CONCLUSIONS: High DAS-28 identifies patients with alterations in HDL characteristics. Plasma levels of apo A-I can be used as a marker of arterial stiffness in RA.