Browse

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

ID PMID Title PublicationDate abstract
29431119 Hypermetabolic macrophages in rheumatoid arthritis and coronary artery disease due to glyc 2018 Jul OBJECTIVES: Accelerated atherosclerotic disease typically complicates rheumatoid arthritis (RA), leading to premature cardiovascular death. Inflammatory macrophages are key effector cells in both rheumatoid synovitis and the plaques of coronary artery disease (CAD). Whether both diseases share macrophage-dependent pathogenic mechanisms is unknown. METHODS: Patients with RA or CAD (at least one myocardial infarction) and healthy age-matched controls were recruited into the study. Peripheral blood CD14+ monocytes were differentiated into macrophages. Metabolic profiles were assessed by Seahorse Analyzer, intracellular ATP concentrations were quantified and mitochondrial protein localisation was determined by confocal image analysis. RESULTS: In macrophages from patients with RA or CAD, mitochondria consumed more oxygen, generated more ATP and built tight interorganelle connections with the endoplasmic reticulum, forming mitochondria-associated membranes (MAM). Calcium transfer through MAM sites sustained mitochondrial hyperactivity and was dependent on inactivation of glycogen synthase kinase 3b (GSK3b), a serine/threonine kinase functioning as a metabolic switch. In patient-derived macrophages, inactivated pGSK3b-Ser9 co-precipitated with the mitochondrial fraction. Immunostaining of atherosclerotic plaques and synovial lesions confirmed that most macrophages had inactivated GSK3b. MAM formation and GSK3b inactivation sustained production of the collagenase cathepsin K, a macrophage effector function closely correlated with clinical disease activity in RA and CAD. CONCLUSIONS: Re-organisation of the macrophage metabolism in patients with RA and CAD drives unopposed oxygen consumption and ultimately, excessive production of tissue-destructive enzymes. The underlying molecular defect relates to the deactivation of GSK3b, which controls mitochondrial fuel influx and as such represents a potential therapeutic target for anti-inflammatory therapy.
29980577 Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovi 2018 Nov Tetraspanins function as membrane adaptors altering cell-cell fusion, antigen presentation, receptor-mediated signal transduction and cell motility via interaction with membrane proteins including other tetraspanins and adhesion molecules such as integrins. CD82 is expressed in several malignant cells and well described as tumour metastasis suppressor. Rheumatoid arthritis (RA) is based on persistent synovial inflammation and joint destruction driven to a large extent by transformed-appearing activated synovial fibroblasts (SF) with an increased migratory potential. OBJECTIVE: CD82 is upregulated in RA synovial fibroblasts (RASF) compared with osteoarthritis (OA) SF as well as within RA compared with OA synovial lining layer (LL) and the role of CD82 in RASF was evaluated. METHODS: CD82 and integrin immunofluorescence was performed. Lentiviral CD82 overexpression and siRNA-mediated knockdown was confirmed (realtime-PCR, Western blot, immunocytochemistry). RASF migration (Boyden chamber, scrape assay), attachment towards plastic/Matrigel, RASF-binding to endothelial cells (EC) and CD82 expression during long-term invasion in the SCID-mouse-model were evaluated. RESULTS: CD82 was induced by proinflammatory stimuli in SF. In RA-synovium, CD82 was expressed in RASF close to blood vessels, LL, sites of cartilage invasion and colocalised with distinct integrins involved in tumour metastasis suppression but also in RA-synovium by RASF. CD82 overexpression led to reduced RASF migration, cell-matrix and RASF-EC adhesion. Reduced CD82 expression (observed in the sublining) increased RASF migration and matrix adhesion whereas RASF-EC-interaction was reduced. In SCID mice, the presence of CD82 on cartilage-invading RASF was confirmed. CONCLUSION: CD82 could contribute to RASF migration to sites of inflammation and tissue damage, where CD82 keeps aggressive RASF on site.
29545451 Flares in Patients with Rheumatoid Arthritis after Total Hip and Total Knee Arthroplasty: 2018 May OBJECTIVE: Rates of total knee arthroplasty (TKA) and total hip arthroplasty (THA) remain high for patients with rheumatoid arthritis (RA), who are at risk of flaring after surgery. We aimed to describe rates, characteristics, and risk factors of RA flare within 6 weeks of THA and TKA. METHODS: Patients with RA were recruited prior to elective THA and TKA surgery and prospectively followed. Clinicians evaluated RA clinical characteristics 0-2 weeks before and 6 weeks after surgery. Patients answered questions regarding disease activity including self-reported joint counts and flare status weekly for 6 weeks. Per standard of care, biologics were stopped before surgery, while glucocorticoids and methotrexate (MTX) were typically continued. Multivariable logistic regression was used to identify baseline characteristics associated with postsurgical RA flares. RESULTS: Of 120 patients, the mean age was 62 years and the median RA duration 14.8 years. Ninety-eight (82%) met 2010/1987 American College of Rheumatology/European League Against Rheumatism criteria, 53 (44%) underwent THA (and the rest TKA), and 61 (51%) were taking biologics. By 6 weeks, 75 (63%) had flared. At baseline, flarers had significantly higher disease activity (as measured by the 28-joint Disease Activity Score), erythrocyte sedimentation rate, C-reactive protein, and pain. Numerically more flarers used biologics, but stopping biologics did not predict flares, and continuing MTX was not protective. A higher baseline disease activity predicted flaring by 6 weeks (OR 2.12, p = 0.02). CONCLUSION: Flares are frequent in patients with RA undergoing arthroplasty. Higher baseline disease activity significantly increases the risk. Although more patients stopping biologics flared, this did not independently predict flaring. The effect of early postsurgery flares requires further study.
29372349 Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets, cytokines and ne 2018 May To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.
30362424 [Analysis of the interrelation between immune factors and inflammatory markers, and the co 2018 SOct This review presents relevant information about development and course of chronic heart failure (CHF) associated with rheumatoid arthritis (RA). One of the most discussed issues is the effect of systemic inflammatory process on prognosis of CHF. The review focused on current evidence for significance of this comorbidity in CHF. The diagnostic role of current immune markers, such as galectin 3, pentraxin 3, growth differentiation factor 15, and osteopontin was described. The review discussed the significance of antiinflammatory therapy for prognosis of CHF in the presence of systemic diseases. Possible beneficial effects of the basis therapy for RA on CHF outcomes were assessed. The authors noted a positive prognostic significance of methotrexate for the risk of decompensated CHF.
29848137 Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between 2019 May Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.
29709544 Identification and suppression of epidermal growth factor receptor variant III signaling i 2018 Jun Epidermal growth factor receptor (EGFR) signaling has been reported to play a vital role in the pathogenesis of rheumatoid arthritis (RA). In current study, we sought to observe whether the active immunization induced by the mimotope could recognize EGFR, inhibit their signaling and disrupt the pathogenic behavior of fibroblast-like synoviocytes (FLS) from RA patients. We prepared a linked EGFR mimotope and performed series of experiments to detect whether the mimotope could induce the desired immune responses. To our surprises, we detected the expression of EGFR variant III (EGFRvIII), but not EGFR in the synovial tissues and FLS from patients with aggressive RA by the linked EGFR mimotope-induced antibodies (LEMIA). Meanwhile, LEMIA could inhibit the signaling caused by the autophosphorylation of EGFRvIII in the FLS. The proliferation, migration, invasion and anti-apoptosis capabilities of the EGFRvIII-expressed FLS were disrupted by LEMIA. These results suggest that EGFRvIII signaling may participate in the malignant behaviors of FLS from aggressive RA. Meanwhile, the linked EGFR mimotope could be used to detect the expression of EGFRvIII and developed to be a potential therapy agent against the aggressive FLS.
29167154 Implementation of the EULAR cardiovascular risk management guideline in patients with rheu 2018 Apr The updated European League Against Rheumatism (EULAR) guideline recommends cardiovascular disease (CVD) risk assessment at least once every 5 years in all patients with rheumatoid arthritis (RA). This viewpoint starts with a literature overview of studies that investigated the level of CVD risk factor (CVD-RF) screening in patients with RA in general practices or in outpatient clinics. These studies indicate that CVD-RF screening in patients with RA is marginally applied in clinical practice, in primary as well as secondary care. Therefore, the second part of this viewpoint describes an example of the successful implementation of the EULAR cardiovascular disease risk management (CVRM) guideline in patients with RA in a region in the south of the Netherlands where rheumatologists and general practitioners (GPs) closely collaborate to manage the cardiovascular risk of patients with RA. The different components of this collaboration and the responsibilities of respectively primary and secondary care professionals are described. Within this collaboration, lipid profile was used as an indicator to assess whether CVD-RF screening was performed in the previous 5 years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined in the previous 5 years. As part of routine quality control, a reminder was sent to the GP in case a patient with RA was not screened. After sending the reminder letter, in 88% of all patients with RA, CVD risk assessment was performed. This collaboration can be seen as good practice to provide care in line with the EULAR guideline.
29288974 Jobelyn(®) attenuates inflammatory responses and neurobehavioural deficits associated wit 2018 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn(®) (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn(®) attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions.
29436473 High erythrocyte levels of the n-6 polyunsaturated fatty acid linoleic acid are associated 2018 Jul OBJECTIVES: Findings relating to dietary intake of n-3 polyunsaturated fatty acids (PUFA) and risk of rheumatoid arthritis (RA) are mixed. Erythrocyte membrane PUFA is an accurate objective biomarker of PUFA status; however, there are little data on erythrocyte membrane PUFA and risk of RA. The objective was therefore to compare erythrocyte membrane PUFA between pre-RA individuals and matched controls from a population-based sample, and specifically to test the hypothesis that higher levels of longer chain n-3 PUFA are associated with lower risk of RA. METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large European prospective cohort study of apparently healthy populations. We undertook a nested case-control study by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts in Italy and Spain. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Conditional logistic regression analysis was used to estimate associations of PUFA with the development of RA, adjusting for potential confounders including body mass index, waist circumference, education level, physical activity, smoking status and alcohol intake. RESULTS: The study analysed samples from 96 pre-RA subjects and 258 matched controls. In this analysis, the median time to diagnosis (defined as time between date of blood sample and date of diagnosis) was 6.71 years (range 0.8-15). A significant inverse association was observed with n-6 PUFA linoleic acid (LA) levels and pre-RA in the fully adjusted model (highest tertile: OR 0.29; 95% CI 0.12 to 0.75; P for trend 0.01). No association was observed with any individual n-3 PUFA, total n-3 PUFA or total n-3:n-6 ratio. CONCLUSIONS: Erythrocyte levels of the n-6 PUFA LA were inversely associated with risk of RA, whereas no associations were observed for other n-6 or n-3 PUFA. Further work is warranted to replicate these findings and to investigate if lower LA levels are a bystander or contributor to the process of RA development.
29148420 The expression of mRNA for peptidylarginine deiminase type 2 and type 4 in bone marrow CD3 2018 Mar OBJECTIVES: Antibodies directed to citrullinated proteins are highly specific for rheumatoid arthritis (RA). Citrullination is catalyzed by peptidylarginine deiminase (PAD) enzymes. The current study examined the mRNA expression of PADI2 and PADI4 in bone marrow (BM) CD34+ cells from RA patients. METHODS: CD34+ cells were purified from BM samples obtained from 48 RA patients and from 30 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The expression of mRNAs for PADI2, PADI4 and Sp1 was examined by quantitative reverse transcription PCR. RESULTS: The expression of mRNA for PADI2 was significantly higher in RA BM CD34+ cells than OA BM CD34+ cells. The expression of mRNAs for PADI4 and Sp1 in RA BM CD34+ cells appeared to be increased compared to OA BM CD34+ cells, although it did not reach the statistical significance. The levels of mRNAs for PADI2, PADI4 and Sp1 were not correlated with serum C-reactive protein or with the administration of methotrexate or oral steroids. Finally, the level of PADI2 mRNA as well as that of PADI4 mRNA was significantly correlated with the level of Sp1 mRNA in RA BM CD34+ cells. CONCLUSIONS: These results indicate that the mRNA expression of PADI2, PADI4 and Sp1 is upregulated in RA BM CD34+ cells independently of the systemic inflammation or treatment regimen. Moreover, the data suggest that the enhanced mRNA expression of PADI2 and PADI4 in BM CD34+ cells might be a result of the enhanced expression of Sp1 gene in RA BM CD34+ cells.
29593187 A case of interstitial pneumonia associated with anti-PL-7 antibody in a patient with rheu 2018 A 65-year-old female had been treated rheumatoid arthritis (RA), interstitial pneumonia (IP) and nephrotic syndrome with prednisolone and cyclosporine. She was emergently admitted to our hospital due to the worsening exertional dyspnea and severe hypoxemia. Chest computed tomography (CT) showed new diffuse ground-glass opacities (GGOs) with slight consolidations along with bronchovascular bundle were observed in addition to pre-existing reticular shadows in both lungs with lower lobe-predominance. An acute exacerbation (AE) of pre-existing IP triggered by an infection was suspected, and the treatment with antibiotics and corticosteroid pulse therapy improved her general condition and chest radiological findings. Because some auto-antibodies associated with acute/subacute onset IP have recently become available in clinic, we examined those including anti-aminoacyl tRNA synthetase (ARS) antibodies, and found that she was positive for anti-PL-7 antibody. We diagnosed her anti-synthetase syndrome (ASS) without symptom of myositis, and her IP was considered to be ASS-related. The careful consideration is necessary to precisely diagnose and treat the patients with RA-associated interstitial lung diseases as the several etiologies may be overlapped in the same patient. J. Med. Invest. 65:147-150, February, 2018.
29350637 Clinical utility of eco-color-power Doppler ultrasonography and contrast enhanced magnetic 2018 Jan 19 With the introduction of new biologics such as anti-TNF-alpha antibodies and other therapies in the treatment of inflammatory arthritis, capable of halting joint destruction and functional disability, there are new pressures on diagnostic and prognostic imaging. Early demonstration of pre-erosive inflammatory features and monitoring of the long-term effects of treatment are becoming increasingly important. Early detection of synovitis offers advantages in terms of allowing early instigation of therapy and may allow the identification of those patients displaying more aggressive disease who might benefit from early intervention with expensive DMARD therapy. Advanced imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) have focussed on the demonstration and quantification of synovitis and allow early diagnosis of inflammatory arthropathies such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Synovitis represents a potential surrogate measure of disease activity that can be monitored using either MRI or US; the techniques have, generally, focused on monitoring synovial volume or quality as assessed by its vascularity. However to achieve these goals, standardisation and validation of US and MRI are required to ensure accurate diagnosis, reproducibility and reliability. Each modality has different strengths and weaknesses and levels of validation. This article aims to increase the awareness of radiologists and rheumatologists about this field and to encourage them to participate and contribute to the ongoing development of these modalities. Without this collaboration, it is unlikely that these modalities will reach their full potential in the field of rheumatological imaging. This review is in two parts. The first part addresses the role of US and colour or power Doppler sonography (PDUS) in the detection and monitoring of synovitis in inflammatory arthropathies. The second part will look at advanced MR imaging and Dynamic contrast-enhanced MRI techniques and in particular how they are applied to the monitoring of the disease process.
30328024 Telomere dysfunction-related serological markers and oxidative stress markers in rheumatoi 2018 Dec Rheumatoid arthritis (RA) is an inflammatory autoimmune polyarthritis with progressive destruction of the synovial joints associated with systemic manifestations. RA is characterized by infiltration of the synovial joints with inflammatory immune cells with premature immunosenescence. Shorter telomere length in the peripheral blood cells and increase in the oxidative stress have been detected in patients with RA. The aim of the present study was to study the association of markers of telomere shortening and oxidative stress with RA disease activity. Sixty-one RA patients and 15 healthy controls were enrolled in the study. Demographic data, clinical examination, and disease activity status were evaluated for the RA patients. Serum levels of chitinase and NAG (telomere markers) were determined by biochemical reactions using colloidal chitin and NAG as substrates, respectively. Nitric oxide and superoxide dismutase (oxidative stress markers) were determined colometrically and spectrophotometrically, respectively, in the sera of RA patients and controls. Results were correlated with disease activity. Indices of telomere shortening and oxidative markers were significantly higher in RA patients compared to controls. These indices were correlated with signs of disease activity (including number of swollen and tender joints, DAS-28, and inflammatory markers). Rheumatoid arthritis is a disease in which markers of telomere shortening and elevated oxidant stress correlate with disease activity.
30229649 (1)H NMR Metabolomics Identifies Underlying Inflammatory Pathology in Osteoarthritis and R 2018 Nov 2 Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying etiologies are markedly different. We used (1)H nuclear magnetic resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100 μL SF was analyzed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analyzed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (false discovery rate (FDR) < 0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by (1)H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis.
30411183 Review of Biosimilar Trials and Data on Etanercept in Rheumatoid Arthritis. 2018 Nov 9 PURPOSE OF REVIEW: Etanercept was the first tumour necrosis factor inhibitor approved to treat rheumatoid arthritis (RA) in the United States (US) and Europe. The recent patent expiration of the etanercept originator ENBREL in Europe has facilitated the development of biosimilar products, creating the prospect of reduced treatment costs. In this article, we review the original trials for etanercept in RA to facilitate critical appraisal of biosimilar trial data. RECENT FINDINGS: Two etanercept biosimilars are currently approved in Europe and/or the US, SB4 (Benepali) and GP2015 (Erelzi), having met the pre-specified equivalence criteria for biosimilarity. Trial data demonstrates subtle differences in clinical outcomes and adverse events between the biosimilars and the reference product (RP). The development of etanercept biosimilars may reduce the financial burden of treating RA, but real-world data regarding efficacy and safety in comparison to the RP will be vital to assess for meaningful differences.
28718078 Relationship between daily pain and affect in women with rheumatoid arthritis: lower optim 2018 Feb The aim of the study was to examine the moderating effect of optimism on the relationship between daily pain-daily affect. Fifty-four female patients with rheumatoid arthritis completed self-report measures of optimism (once), daily pain and daily positive and negative affect for 7 consecutive days during hospitalization. Results of multilevel random coefficients modeling demonstrated a significant cross-level interaction for daily negative affect only. Simple slopes analysis revealed that low optimism was related to a stronger positive relationship between daily pain and daily negative affect, whereas this effect was insignificant for higher optimism. High optimism was also related to higher daily positive affect, regardless of pain level. These findings suggest that low optimism may be a vulnerability factor in the daily pain-daily affect relationship rather than high optimism acting as a protective factor.
29439320 Of patents and patent disputes - The TNFα patent files. Part 2: Enbrel, Remicade, Cimzia 2018 Feb 5 This article is the second part of a trilogy that discusses IP issues related to anti-Tumor Necrosis factor α (TNFα) biologics. TNFα is the world's most valuable target, with accumulated sales of TNFα biologics of 34 bn USD in 2014. While in the first part of this trilogy, Humira was discussed, this second parts discusses the patent strategies of Enbrel, Remicade, Cimzia and Simponi.
29652702 Microwave Radiometry-Derived Thermal Changes of Small Joints as Additional Potential Bioma 2018 Aug OBJECTIVE: A prospective pilot study was performed using microwave radiometry (MR), a noninvasive method detecting in-depth tissue temperature, to evaluate whether temperature-of-small-joint-derived scores correlate to parameters commonly used to assess disease activity in rheumatoid arthritis (RA). METHODS: Ten patients with active, untreated RA underwent clinical and laboratory assessments and joint ultrasound and MR of hand and foot small joints at baseline and at 15, 30, and 90 days after treatment onset. Mixed-model analysis for repeated measures was used to compare patient characteristics in sequential visits. Twenty age- and sex-matched healthy individuals served as control subjects. RESULTS: Using 1248 MR-derived separate recordings from patients' joints, several thermoscores involving different joint combinations were created. When compared with clinical and ultrasound data, the best performing thermoscore involved temperatures of 16 joints (second to fifth metacarpal and proximal interphalangeal joints, bilaterally). This thermoscore correlated to the 28-joint Disease Activity Score-C-reactive protein, tender and swollen joint counts, patient's visual analog scale (all P ≤ 0.02), and the standard 7-joint ultrasound score (P < 0.03) and could also discriminate patients in high (mean, 9.2 [SD, 5.6]) or moderate (7.1 [SD, 3.5]) versus low disease activity/remission (4.2 [SD, 1.8]) (P ≤ 0.01) or healthy subjects (5.0 [SD, 1.7]) (P = 0.002). CONCLUSIONS: Microwave radiometry-derived increased in-depth temperature indicative of local inflammation of small joints may serve as an additional biomarker in RA. Optimization of MR-based methods may result in objective assessments of RA disease activity in clinical practice.
30569216 Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Resp 2019 Apr The aim of this study, based on a post hoc analysis of the data set used in the RAPID 1 trial, focuses on the associations between metacarpal bone mineral density, as estimated by digital X-ray radiogrammetry (DXR), and clinical remission as well as ACR70-Response in rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP). The trial evaluates a total of 345 RA patients treated with methotrexate versus CZP 200 mg versus CZP 400 mg. All patients underwent X-rays of the hand at baseline and week 52 as well as computerized calculations of bone mineral density (BMD) by DXR. Clinical remission was defined as DAS28 < 2.6. ACR70-Response was also evaluated. The radiological assessment of disease progression was estimated using the modified total Sharp Score. The mean difference for DAS28 was observed for patients treated with CZP 400 mg (median: - 3.53, minimum: - 6.77; maximum: + 0.48) and CZP 200 mg (median: - 3.13, minimum: - 6.37; maximum: - 0.52) compared to the methotrexate group (median - 2.41, minimum: - 4.76; maximum: + 0.31). The DXR-BMD showed a minor bone loss for the treatment groups undergoing therapy with CZP 200 mg (median: - 0.009 g/cm(2), minimum: - 0.059 g/cm(2); maximum: + 0.095 g/cm(2)) and CZP 400 mg (median: - 0.008 g/cm(2), minimum: - 0.064 g/cm(2); maximum: + 0.080 g/cm(2)). The methotrexate group presented an advanced periarticular metacarpal bone loss as measured by DXR-BMD (median: - 0.024 g/cm(2), minimum: - 0.102 g/cm(2); maximum: + 0.057 g/cm(2)). In the case of clinical remission and ACR70-Response, no significant change of the DXR-BMD was observed for both CZP groups. The study highlights that patients treated with CZP show a less accentuated periarticular bone loss as estimated by DXR in comparison to patients with methotrexate plus placebo. In addition, patients with clinical remission and ACR70-Response revealed no periarticular demineralisation.