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ID PMID Title PublicationDate abstract
31382595 Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid A 2019 Aug 3 Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their combination has not been explored before. Therefore, this study aimed to investigate the effect of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice were randomly assigned to four groups; group I received an intravenous injection of mouse bone marrow-derived MSCs, while group II received an intraperitoneal injection of IL-4. Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS). A fifth group of healthy mice served as the normal healthy control. To assess changes induced by different treatments, levels of RA-associated inflammatory cytokines and biomarkers were measured in the serum, knee joints, and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features of knee joints were analyzed for all groups. Results showed that combined MSC and IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values of healthy controls. This was evident by the decrease in the levels of rheumatic factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 80, and 71%, respectively, compared to the diseased group. Moreover, tumor necrosis factor-alpha (TNF- α) and monocyte chemoattractant protein-1 (MCP-1) levels decreased by 63 and 68%, respectively. Similarly, our gene expression data showed improvement in mice receiving combined therapy compared to other groups receiving single treatment, where cartilage oligomeric matrix protein (Comp), tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, respectively. Collectively, treatment with a combined therapy of MSC and IL-4 might have an efficient therapeutic effect on arthritis. Thus, further studies are needed to assess the potential of different MSC populations in conjugation with IL-4 in the treatment of experimental arthritis.
30917251 [Indices of cell-mediated immunity in rheumatoid arthritis: the role of cytomegalovirus in 2019 The pathogenesis of rheumatoid arthritis (RA) is driven by a combined action of genetic and environmental factors, which can upset the balance between the effector and regulatory components of the immune system. An important actor in maintaining such balance is T cells, especially regulatory T lymphocytes (Treg), but the mechanisms behind the functioning of T cell subpopulations and the roles of individual etiological factors in RA have not been fully elucidated. This study aimed to investigate the indices of cell-mediated immunity, especially T- and Treg cells, in RA patients depending on the disease activity and presence of cytomegalovirus (CMV) infection. The expression of membrane and intracellular molecular markers of lymphocytes was estimated by multicolor flow cytometry. The content of antibodies to CMV in blood plasma was measured by enzyme immunoassays. Patients with RA had reliably reduced numbers of cells with the phenotypes CD4+FOXP3+, CD4+CD25+FOXP3+ correlating with the stage of RA activity. RA patients with CMV infection showed a reduction in the number of regulatory T cells (Treg), CD3+ T lymphocytes, CD3+CD8+ cells in peripheral blood. At the same time, RA involved a rise in the level of B cells and CD4+CD25+ Т cells. The level of antibodies to CMV was observed to grow in line with RA activity. Thus, the data obtained suggest that the presence of CMV infection can significantly influence the state of individual lymphocyte subpopulations during RA development.
31295951 Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis. 2019 Jul 10 Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA-namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa-environment interaction.
31602899 [Study advances in regulation effect of Tripterygium wilfordii and its extracts on innate 2019 Aug Rheumatoid arthritis( RA) is an autoimmune disease characterized by chronic and aggressive polyarthritis. The innate immunity mechanism plays a key role in the pathogenesis of RA. Tripterygium wilfordii and its extracts have regulatory effects on innate immune cells including macrophages,dendritic cells,neutrophils,mast cells,NK cells,NKT cells,etc.,as well as a variety of innate immune molecules including cytokines,adhesion molecules,patterns recognition receptor( PRR) and the complement molecules,showing a regulatory effect in the pathogenesis of RA innate immunity. In this paper,the recent domestic and foreign researches on the pathogenesis of RA with innate immunity involved were reviewed and the research status of T. wilfordii and its extracts on the regulation of innate immunity involved in RA was summarized.
30718103 Radiological patterns of pulmonary involvement may predict treatment response in rheumatoi 2019 Mar BACKGROUND: There have been no reports on the relationship between lung radiological patterns and rheumatoid arthritis (RA) disease activity or RA treatment response in patients with RA-associated lung disease (RA-LD). METHODS: Patients with RA-LD who underwent treatment for RA from April 2005 to March 2015 were retrospectively evaluated. RA-LD patients were divided into three groups based on high-resolution computed tomography (HRCT) patterns [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis]. The disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the response of RA to treatment, as measured by the European League Against Rheumatism (EULAR) response criteria, were investigated. RESULTS: A total of 77 patients (21 with UIP, 23 with NSIP, and 33 with bronchiolitis) were enrolled. Median scores (interquartile range) on the DAS28-ESR at baseline were 5.27 (4.76-5.74), 5.48 (4.24-6.34), and 5.04 (3.90-5.66) for UIP, NSIP, and bronchiolitis, respectively; there were no statistical differences between the three groups (p = 0.412). One year after baseline, 19 (90%), 14 (61%), and 19 (58%) of patients in the UIP, NSIP, and bronchiolitis groups, respectively, were considered good or moderate responders, as evaluated using the EULAR response criteria; there was a significant difference between these three groups (p = 0.014). Multiple logistic regression analysis revealed that the UIP pattern was significantly associated with good or moderate response to RA treatment 1 year after baseline (p = 0.012). CONCLUSIONS: These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy.
30511171 [Higher prevalence of depressive and anxiety symptoms in early arthritis patients in compa 2019 Nov BACKGROUND: Many studies and registry data confirm that depression, often associated with anxiety disorders is very often found in patients with rheumatoid arthritis (RA). To what extent these psychiatric disorders are already relevant at a very early stage of the disease, has currently not been adequately investigated. METHODS: In this study 176 patients with early joint symptoms (<1 year) were surveyed in an early arthritis consultation (EAC). The hospital anxiety and depression scale (HADS) was completed by the patients to examine the prevalence of depressive and anxiety symptoms. The results were compared to normative data of the general German population and between the diagnosis groups. RESULTS: With 47.7% the prevalence of global distress for EA patients was almost twice as high compared to the corresponding group from the general population. This was also confirmed for depressive and anxiety symptoms. The EA patients without confirmed evidence of musculoskeletal inflammatory rheumatic disease (RD) showed nearly the same point prevalence as patients with confirmed RD. In multiple logistic regression the health assessment questionnaire (HAQ) was positively associated with global distress (odds ratio, OR 3.63) while the visual analogue scale (VAS) for global disease activity was positively associated with symptoms of depression (OR 1.03). Female EA patients (OR 5.45) appear to have a higher probability for experiencing corresponding symptoms, whereas patients over 60 years old appear to have less anxiety than younger patients (OR 0.11). CONCLUSION: The high prevalence of symptoms of depression and anxiety in EA patients compared to the general population is a challenge for rheumatologists, orthopedists and general practitioners, particularly with respect to the differentiation of possible psychosomatic components in noninflammatory joint complaints. The results suggest that screening for psychiatric problems in patients with rheumatism should be evaluated as soon as possible as these can have a great impact on the perception of pain and physical functional status from the very beginning.
31519956 A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteo 2019 Sep 13 While patients with rheumatoid arthritis (RA) sometimes demonstrate thyroidal illness, the role of thyroid hormones in inflamed synovial tissue is unknown. This is relevant because thyroid hormones stimulate immunity, and local cells can regulate thyroid hormone levels by deiodinases (DIO). The study followed the hypothesis that elements of a thyroid hormone network exist in synovial tissue. In 12 patients with RA and 32 with osteoarthritis (OA), we used serum, synovial fluid, synovial tissue, and synovial fibroblasts (SF) in order to characterize the local thyroid hormone network using ELISAs, immunohistochemistry, imaging methods, tissue superfusion studies, cell-based ELISAs, flow cytometry, and whole genome expression profiling. Serum/synovial fluid thyroid hormone levels were similar in RA and OA (inclusion criteria: no thyroidal illness). The degradation product termed reverse triiodothyronine (reverse T3) was much lower in serum compared to synovial fluid indicating biodegradation of thyroid hormones in the synovial environment. Superfusion experiments with synovial tissue also demonstrated biodegradation, particularly in RA. Cellular membrane transporters of thyroid hormones, DIOs, and thyroid hormone receptors were present in tissue and SF. Density of cells positive for degrading DIOs were higher in RA than OA. TNF increased protein expression of degrading DIOs in RASF and OASF. Gene expression studies of RASF revealed insignificant gene regulation by bioactive T3. RA and OA synovial tissue/SF show a local thyroid hormone network. Thyroid hormones undergo strong biodegradation in synovium. While bioactive T3 does not influence SF gene expression, SF seem to have a relay function for thyroid hormones.
31136605 Reduced IgG titers against pertussis in rheumatoid arthritis: Evidence for a citrulline-bi 2019 BACKGROUND: The antibody response to pertussis vaccination in rheumatoid arthritis is unknown, a concerning omission given the relatively low efficacy of the pertussis vaccine, a rise in pertussis infections, and a general increased susceptibility to infection in rheumatoid arthritis. Additionally, the contributions from an intrinsically dysregulated immune system in rheumatoid arthritis and immune-suppressing medications to the response to pertussis vaccination is poorly defined. This study examines antibody titers against pertussis in vaccinated rheumatoid arthritis patients and controls as well as evaluates potential contributions from demographic factors, immune suppressing medications, and reactivity against citrullinated pertussis. METHODS: Serum IgG titers against native and citrullinated pertussis and tetanus were quantified by enzyme-linked immunosorbent assay in rheumatoid arthritis subjects and controls who were vaccinated within 10 years. Titers were compared by t-test and percent immunity by Fisher's exact test. Multivariable logistic regression was used to identify clinical factors that correlate with native pertussis titers. RESULTS: Compared to controls, rheumatoid arthritis subjects had lower titers against pertussis, but not tetanus, and reduced immunity to pertussis. These results were even more prominent at 5-10 years post-vaccination, when rheumatoid arthritis patients had 50% lower titers than controls and 2.5x more rheumatoid arthritis subjects were not considered immune to pertussis. Multiple logistic regression demonstrated that female sex and methotrexate use, but not TNF inhibiting medications, correlated with reduced immunity to pertussis. Finally, rheumatoid arthritis patients had higher IgG titers against citrullinated pertussis than native pertussis. CONCLUSIONS: Pertussis titers are lower in vaccinated rheumatoid arthritis patients with evidence for contributions from female sex, a citrulline-biased immune response, and methotrexate use.
31359630 Treat-to-target and shared decision making in rheumatoid arthritis treatment: Is it feasib 2019 Sep AIM: Current rheumatoid arthritis (RA) guidelines have incorporated a treat-to-target (T2T) approach and require that it be implemented through shared decision making (SDM). Current discourse has questioned whether collaborative T2T is feasible in RA, in part because of discrepancies in the way that patients and practitioners assess progress and decide whether to consider a change in the current treatment. A previous study found that patients' willingness to change is directly associated with their disease activity (DA) scores. The current study continues this line of research by developing and testing a model that describes the role of DA and illness beliefs on RA patients' progress assessments. METHOD: A questionnaire administered to 156 patients with RA included a self-assessed DA measure (Rapid-4), an illness belief battery (BIPQ), and a progress assessment question. These items populated a descriptive model, based on situation awareness (SA) theory. It posits that progress assessment scores are products of 3 sequential steps: perception, understanding, and forecasting. The first 2 steps were measured by DA scores, the 3rd by illness beliefs. The model was tested using general linear model techniques. RESULTS: All six measures were significantly related to progress assessment scores. The full SA model accounted for over 50% of the variance. The best fitting model included a pain measure at step 1, global disability at step 2, and illness beliefs at step 3. CONCLUSION: Findings suggest that implementing T2T through SDM is feasible, that there is substantial commonality between how patients and practitioners assess progress, and that discrepancies may be complementary and addressed through interaction. The SA model helps to explain previous findings about the influence of illness beliefs on patients' judgments. It is suggested that future studies acknowledge the feasibility of collaborative T2T and focus attention on how it can work more effectively and comprehensively.
30969024 Selective Sexual Dimorphisms in Musculoskeletal and Cardiopulmonary Pathologic Manifestati 2019 Sep OBJECTIVE: To examine and quantify the sexual dimorphism in pathologic features manifested in the musculoskeletal and cardiopulmonary systems and incidence of mortality in the tumor necrosis factor-transgenic (TNF-Tg; Tg3647 strain) mouse model of inflammatory erosive arthritis. METHODS: Kaplan-Meier survival estimates were determined in male and female Tg3647 mice and sex-matched wild-type (WT) littermate mice. Longitudinal and cross-sectional pathologic outcomes in the musculoskeletal and cardiopulmonary systems were assessed via ultrasound, micro-computed tomography, grip strength measurements, histologic and serologic analyses, flow cytometry, and skeletal muscle physiologic measures. RESULTS: Compared to male Tg3647 mice (n = 30), female Tg3647 mice (n = 34) had significantly shorter lifespans (P < 0.001) and exhibited the following pathologic features (n = 4-6 per group; P < 0.05 versus male Tg3647 littermates): gross deficits in body mass and muscle weight, early-onset inflammatory arthritis with severity of end-stage arthritis that was as severe as that seen in male transgenic mice, and early onset and increased severity of inflammatory interstitial lung disease (ILD). Histologically, the ILD observed in Tg3647 mice was characterized by inflammatory cell accumulation and pulmonary arteriole thickening, which was concomitant with the presence of right ventricular hypertrophy, a feature that was also more severe in the female compared to male Tg3647 mice (P < 0.05). No sexual dimorphisms in TNF-induced deficient grip strength, axial skeletal growth, or bone loss were found. Globally, the extent of the pathologic changes observed in female Tg3647 mice was greater than that observed in male Tg3647 mice when each group was compared to their sex-matched WT littermates. CONCLUSION: These findings indicate that TNF selectively drives the early onset of arthritis and progression of pathologic changes in the cardiopulmonary system in female Tg3647 mice. These results in the Tg3647 mouse identify it as a suitable model to better understand the mechanisms underlying sexual dimorphism and cardiopulmonary disease in the setting of inflammatory arthritis and other connective tissue diseases.
30681555 Evaluation of alexithymia in patients affected by rheumatoid arthritis and psoriatic arthr 2019 Jan Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic autoimmune diseases leading to joint damage, functional limitation, and disability and are typically associated with several comorbidities. Alexithymia is a personality trait characterized by a disregulation of emotion processing and regulation of emotions that involves a dissociation of emotional and physical responses to life events. A broad association between alexithymia and symptoms as depression, inflammation, and pain has been demonstrated. We aimed at evaluate an association among inflammatory arthritis, as RA and PsA, and alexithymia, and a possible link with clinical characteristics and disease activity.In this cross-sectional study, we enrolled, from January to December 2017, patients affected by RA or PsA referring to the outpatient's clinic of the Rheumatology Unit of the University of Rome Tor Vergata. The 20-item Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia. Disease activity, function, quality of life, and clinimetric indexes were assessed.A total of 50 RA patients and 51 PsA patients were enrolled. The TAS-20 score showed 38.6% (39/101) patients had alexithymia, 26.7% (27/101) patients were in the borderline of alexithymia and 34.7% (35/101) patients did not have alexithymia. A statistical significant association was observed between alexithymia and inflammatory indices (ESR: P = .029, CRP: P = .043) and between alexithymia and clinimetric parameters (ptVAS, pVAS, GH, P < .0001 for all comparisons). A significant trend of association has been demonstrated between alexithymia and female gender and concomitant steroid therapy. No correlations among variables such as age, duration of disease, and comorbidities and alexithymia status were observed.This study suggests that alexithymia assessment should be a part of the comprehensive management of RA and PsA patients.
31926497 Biochemical Analysis of C-X-C Motif Chemokine Ligand 10 (CXCL10) as a Biomarker in Patient 2019 Jul Rheumatoid arthritis (RA) is characterized by chronic inflammation and synovial hyperplasia that eventually leads to the destruction of the joints. CXCL10 has been originally identified as a pro-inflammatory chemokine that mediate leukocyte trafficking and modulate innate and adaptive immune responses. It plays a critical role in the inflammatory response and is involved in several biological processes. The aim of the study was to assess the diagnostic efficacy of serum CXCL10 levels in early RA patients. Patients and methods: The study included 60 RA patients; 30 of them were early diagnosed, and 30 longstanding RA and 30 healthy controls. Clinical examination was done for all patients. Measurement of serum CXCL10 level was done by ELISA, while assessment of disease activity in patients was done using disease activity score (DAS-28). Serum levels of CXCL10 were significantly higher in RA patients than controls (P < 0.001), and was more elevated in early diagnosed than longstanding RA patients, with a a significant positive correlation with DAS-28 ESR (r=0.361, P=0.005), number of tender joint (r=0.319, P=0.013), and number of swollen joint (r=0.280, P=0.030). A cutoff at 470.0 pg/ml was able to recognize longstanding RA with a sensitivity of 88.3% and a specificity of 90% , while a cutoff of 793 pg/ml was able to diagnose early RA with 65% sensitivity and 77% specificity (P=0.009). in conclusion, serum CXCL10 may be a useful biomarker for diagnosis of early RA and determination of disease activity.
31414744 Plasma Long Non-Coding RNA Expression Profiles in Patients with Rheumatoid Arthritis. 2019 Aug 1 BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have attracted substantial attention owing to their unforeseen critical roles in a wide range of biological processes. The aim of our study was to provide an overview of lncRNA expression profiles in plasma of RA patients. METHODS: The Agilent LncRNA + mRNA Human Gene Expression Microarray V4.0 was employed to determine differentially expressed (DE) lncRNAs and mRNAs in plasma of four female newly diagnosed and DMARD-naïve RA patients and four female age-matched healthy controls. The KOBAS (KEGG Orthology Based Annotation System) software was applied to determine the gene ontology (GO) terms and pathway in which the DE mRNAs were enriched. Furthermore, a lncRNA-mRNA co-expression network was constructed according to the correlation between DE lncRNAs and mRNAs. RESULTS: Compared with healthy controls, a total of 289 DE lncRNAs (169 up-regulated and 120 down-regulated) and 468 DE mRNAs (280 up-regulated and 188 down-regulated) were found in the plasma of patients with RA. Bioinformatics analysis indicated that the DE mRNAs might be involved in the pathogenesis of RA mainly through platelets. In addition, a co-expression network composed of 229 network nodes and 340 connections between 116 lncRNAs and 113 mRNAs was constructed. CONCLUSIONS: We characterized the plasma lncRNA expression profiles in RA patients for the first time. Our results could shed new light on the pathogenesis of RA and help identify lncRNAs as novel diagnostic biomarkers and therapeutic targets for RA.
31409388 Comparative study of the inhibitory effect on bone erosion progression with denosumab trea 2019 Aug 13 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints, causes joint destruction, and leads to physical disability. Advances in the treatment of RA, such as biologic disease-modifying anti-rheumatic drugs (DMARDs), have provided better clinical outcomes, including the achievement of remission for patients with RA, but some patients cannot receive these treatments because of their side effects and high cost, and not all patients achieve remission. Although the efficacy of denosumab, which is a human IgG2 monoclonal antibody with a high affinity for the receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), in the treatment of RA has been reported in clinical trials, the efficacy of denosumab in both preventing joint destruction and improving disease activity has not been evaluated in a real-world setting. METHODS/DESIGN: This open-label, randomized, parallel-group study will compare the continued use of conventional synthetic DMARDs (csDMARDs) alone with the combined use of csDMARDs and denosumab in patients whose RA is treated with csDMARDs. In total, 44 patients with RA will be randomly assigned to receive additional treatment with denosumab or to continue RA treatment without additional denosumab. The duration of the intervention will be 12 months. To analyze bone erosion and bone micro-architecture precisely, high-resolution peripheral quantitative computed tomography (HR-pQCT) will be performed every 6 months. The primary endpoint is changes in the depth of bone erosion as measured by HR-pQCT from baseline to 6 months. Important secondary endpoints are the changes from baseline in the width and volume of bone erosion as measured by HR-pQCT and changes from baseline in the depth of bone erosion at 12 months. Changes in bone micro-architecture will also be analyzed as an exploratory endpoint. DISCUSSION: The results of this study are expected to provide strong evidence regarding the usefulness of denosumab for the treatment of RA. Moreover, by using HR-pQCT, this study will also reveal the effect of denosumab not only on bone erosion but also on bone micro-architecture. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000030575 on December 26, 2017.
31462329 Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with r 2019 Aug 28 BACKGROUND: Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers. METHODS: A total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment. RESULTS: The study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10(- 5) ≤ P ≤ 4.07 × 10(- 4)) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK. CONCLUSIONS: This study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers.
30824997 [Improvement of prognosis by timely treatment : Requirement: initial presentation within 6 2019 Jun Rheumatoid arthritis (RA) is one of the most frequent chronic inflammatory rheumatic diseases and when untreated leads to chronic tissue destruction and increased mortality. Due to innovative systemic treatment strategies established over the last 20-25 years, the prognosis has considerably improved in terms of disease and socioeconomic burdens, symptoms, long-term prognosis, ability to work and mortality; however, as a rule a prerequisite is long-term and continuous treatment. A medicinal cure of RA is still not in view. For many patients this means the long-term use of very expensive medications. In addition to hemato-oncology, rheumatology has become the second most expensive discipline in Germany in terms of cost per patient. Convincing data from many studies imply that an early start of treatment within the first few weeks after clinical onset of symptoms improves the prognosis, reduces the necessity for expensive drugs and thereby considerably decreases medical costs. This results in the requirement that every patient with symptoms of arthritis must be seen by a rheumatologist within the first 6 weeks following initial manifestation of the disease. Such an improvement in treatment can only be achieved in Germany if the numbers of rheumatologists and trained healthcare professionals in practices such as clinics are considerably increased. This is not only in the interests of patients but also in the interests of the health insurance companies because the investment in the healthcare infrastructure with internistic rheumatologists will result in substantial economic benefits for the cost bearer. It must be the common task of all players in healthcare policy, cost bearers and internistic rheumatologists to provide optimal conditions in medical as well as economical terms.
30587434 The effectiveness of joint-protection programs on pain, hand function, and grip strength l 2019 Apr STUDY DESIGN: Systematic review with meta-analysis. INTRODUCTION: Joint protection (JP) has been developed as a self-management intervention to assist people with hand arthritis to improve occupational performance and minimize joint deterioration over time. PURPOSE OF THE STUDY: We examined the effectiveness between JP and usual care/control on pain, hand function, and grip strength levels for people with hand osteoarthritis and rheumatoid arthritis. METHODS: A search was performed in 5 databases from January 1990 to February 2017. Two independent assessors applied Cochrane's risk of bias tool, and a Grading of Recommendations Assessement, Development and Evaluation (GRADE) approach was adopted. RESULTS: For pain levels at short term, we found similar effects between JP and control standardized mean difference (SMD; -0.00, 95% confidence interval [CI]: -0.42 to 0.42, I(2) = 49%), and at midterm and long-term follow-up, JP was favored over usual care SMD (-0.32, 95% CI: -0.53 to -0.11, I(2) = 0) and SMD (-0.27, 95% CI: -0.41 to -0.12, I(2) = 9%), respectively. For function levels at midterm and long-term follow-up, JP was favored over usual care SMD (-0.49, 95% CI: -0.75 to -0.22, I(2) = 34%) and SMD (-0.31, 95% CI: -0.50 to -0.11, I(2) = 56%), respectively. For grip strength levels, at long term, JP was inferior over usual care mean difference (0.93, 95% CI: -0.74 to 2.61, I(2) = 0%). CONCLUSIONS: Evidence of very low to low quality indicates that the effects of JP programs compared with usual care/control on pain and hand function are too small to be clinically important at short-, intermediate-, and long-term follow-ups for people with hand arthritis.
30587928 Tocilizumab in the treatment of rheumatoid arthritis: an evidence-based review and patient 2019 Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and systemic manifestations, such as anemia, fatigue, osteoporosis, and increased risk for cardiovascular diseases. The pathogenesis of RA is driven by a complex network of proinflammatory cytokines, with a pivotal role of IL-6 and tumor necrosis factor (TNF). The management of RA has been dramatically changed during the last years by the introduction of a treat-to-target approach aiming to achieve an acceptable disease control. Nowadays, TNF inhibitors (TNFis) are the most frequently prescribed class of biologic therapies, but the significant proportion of patients experiencing the failure of a TNFi led to the development of alternative therapeutic options targeted on different pathways. Considering the increasing number of targeted therapeutic options for RA, there is a growing interest in the identification of potential predictors of clinical response to each available mechanism of action, with the aim to drive the management of the disease toward a personalized approach according to the concept of precision medicine. Tocilizumab (TCZ) is the first humanized anti-IL-6 receptor subunit alpha (anti-IL-6R) monoclonal antibody approved for the treatment of RA refractory to methotrexate or TNFis. TCZ inhibits both the cis- and trans-signaling cascades involving the Janus kinase-signal transducer and the activator of transcription pathway, playing a crucial role in modulating not only joint inflammation but also the previously mentioned extra-articular manifestations and comorbidities of RA, such as fatigue, anemia, bone loss, depression, type 2 diabetes, and increased cardiovascular risk. In this review, moving from pathogenetic insights and evidence-based clinical data from randomized controlled trials and real-life observational studies, we will discuss the drivers for the selection of patient candidates to receive TCZ, in order to clarify the current positioning of this drug in the treatment algorithm of RA.
31076346 Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-ad 2019 May BACKGROUND: Bone destruction is one of many severe complications that occurs in patients with rheumatoid arthritis (RA) and current therapies are unable to cure this manifestation. This study here aims to determine whether GMSC can directly inhibit osteoclast formation and eventually attenuate osteoclastogenesis and bone erosion in an inflammatory milieu. METHOD: GMSC were co-cultured with osteoclast precursors with or without CD39 inhibitor, CD73 inhibitor or adenosine receptors inhibitors pretreatment and osteoclast formation were evaluated in vitro. 2×10^6 GMSC per mouse were transferred to CIA mice and pathology scores, the frequency of osteoclasts, bone erosion in joints were assessed in vivo. FINDING: GMSC but not control cells, markedly suppressed human or mice osteoclastogenesis in vitro. GMSC treatment also resulted in a dramatically decreased level of NF-κB p65/p50 in osteoclasts in vitro. Infusion of GMSC to CIA significantly attenuated the severity of arthritis, pathology scores, frequency of osteoclasts, particularly bone erosion, as well as a decreased expression of RANKL in synovial tissues in vivo. Blockade of CD39/CD73 or adenosine receptors has significantly abrogated the suppressive ability of GMSC in vitro and therapeutic effect of GMSC on bone erosion during CIA in vivo. INTERPRETATION: GMSC inhibit osteoclast formation in vitro and in vivo partially via CD39-CD73-adenosine signals. Manipulation of GMSC may have a therapeutic implication on rheumatoid arthritis and other bone erosion related diseases. FUND: This study was supported by grants from the National Key R&D Program of China (2017YFA0105801 to F.H); the Zhujiang Innovative and Entrepreneurial Talent Team Award of Guangdong Province (2016 ZT 06S 252 to F·H) and National Institutes of Health (R01 AR059103, R61 AR073409 and NIH Star Award to S.G.Z).
29998832 Does early seronegative arthritis develop into rheumatoid arthritis? A 10-year observation 2019 Jan OBJECTIVES: To investigate the 10-year clinical course of patients with seronegative arthritis with the emphasis of reclassification of diagnoses when applicable. METHODS: A total of 1030 patients including 435 seronegative cases were classified as early RA in 1997-2005 at Jyväskylä Rheumatology Centre and prospectively scheduled for a ten-year follow-up. Clinical data from the follow-up visits and the case-reports until and including the 10-year visit or death, whichever happened earlier, were retrospectively collected and reviewed with re-classification of the cases when applicable. Descriptive statistics were used. RESULTS: Among the 435 seronegative cases (69 % women, baseline mean age was 59 years), 13 (13/435 [3%]) could be reclassified as seropositive or erosive RA: 4 turned seropositive (2 for ACPA and 2 for RF [> 2x reference level]) and 9 developed erosions typical for RA. Reclassification revealed 68 (16%) cases of polymyalgia rheumatica, 46 (11%) psoriatic arthritis, 45 (10%) osteoarthritis, 38 (8.7%) spondyloarthritis, 15 (3.4%) plausible reactive arthritis, 10 (2.3%) gout, 17 (3.9%) pseudogout, 6 (1.4%) paraneoplastic arthritis, 6 (1.4%) juvenile arthritis, 2 (0.5%) haemochromatosis, 3 (0.7%) ankylosing spondylitis, 2 (0.5%) giant cell arteritis, and 8 miscellaneous diagnoses. The other 140 patients (32%) could not be reclassified in any clear-cut diagnosis and had features of transient arthritis (n=41), seronegative spondyloarthritis (n=47), while 49 remained unspecified. CONCLUSIONS: Over a 10-year follow-up period, reclassification revealed significant heterogeneity in the diagnosis of seronegative RA. Therefore, seronegative arthritis should not be studied as a homogenous entity.