Cell-cell interactions in synovitis: Endothelial cells and immune cell migration

Leukocyte ingress into the synovium is a key process in the pathogenesis of rheumatoid arthritis and other inflammatory conditions. In this review, the role of endothelial cells in leukocyte extravasation will be discussed, including the role of the most relevant cellular adhesion molecules. These molecules play an important role in mediating leukocyte-endothelial interactions. It is likely that different adhesive pathways are involved in different steps of leukocyte adhesion to and migration through endothelia. Targeting of pathological endothelial function, including leukocyte-endothelial adhesion, may be useful for the future management of inflammatory arthritis

Ophthalmological Manifestations and Tear Investigations in Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. There are only few reports available concerning ophthalmological complications in the course of SSc, although ocular manifestations, e.g., dry eye syndrome (DES), occurs frequently and decreases the quality of life of these patients. Vascular endothelial growth factor (VEGF), the major pro-angiogenic factor, plays a key role in the pathomechanism of SSc. Although elevated levels of VEGF in sera have already been demonstrated, VEGF analysis in tears of patients with SSc has not been performed in previous studies. VEGF in the tears of patients with SSc was found to be decreased by 20%, compared to healthy controls. The reason why the VEGF levels are not elevated in the tears of patients with SSc needs further investigations, as does the sera of the same patients. The cytokine array results revealed a shift in the cytokine profile characterized by the predominance of inflammatory mediators. Our current data depict a group of cytokines and chemokines, which play a significant role in ocular pathology of SSc; furthermore, they might function as excellent candidates for future therapeutic targets in SSc with ocular manifestations

Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

Objective: The aim of this study was to evaluate the efficacy, reasons for switching and drug survival of TNF-α inhibitors (TNFis) used as first- and second-line drugs in ankylosing spondylitis (AS). Methods: Data on patients suffering from AS and treated with at least one TNFi between November 2005 and 2013 were extracted retrospectively from the database of a single clinical centre. Beside demographic data, the disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the response rates (BASDAI50), reasons for switching and survival curves of TNFis were analysed in general and in subgroups of patients treated with each of the available TNFis. The reasons for switching were defined as inefficacy, side effects of the given drug, patient's request and occurrence of extra-articular manifestations. Results: Altogether, 175 patients were on TNFis and 77 of them received at least two TNFis. The patients' age at the initiation of the first TNFi was higher among switchers compared to non-switchers (42.5 ± 12.6 vs. 38.8 ± 11.2 years, p = 0.049); otherwise, gender, disease duration and initial disease activity had no influence on the risk of switching. The decrease of the BASDAI was similar among non-switchers and switchers using either the first or second TNFi, but the response rates to the first and second TNFi were worse in switchers than in non-switchers. Following the failure of the first TNFi, the retention on therapy was unfavourable, especially in patients on infliximab after 1 year of treatment. The main reason for switching from the first drug was inefficacy. The frequency of side effects that led to switching was higher in the infliximab group than in patients treated with other agents. Conclusion: Although the retention rate to a second-line TNFi was somewhat worse than that to the first-line TNFi, the switching of TNFis is a good therapeutic option in AS patients who failed to respond to the first TNFi. © Springer-Verlag 2014

EULAR points to consider for the development, evaluation and implementation of mobile health applications aiding self-management in people living with rheumatic and musculoskeletal diseases

Background: Mobile health applications (apps) are available to enable people with rheumatic and musculoskeletal diseases (RMDs) to better self-manage their health. However, guidance on the development and evaluation of such apps is lacking. Objectives: The objective of this EULAR task force was to establish points to consider (PtC) for the development, evaluation and implementation of apps for self-management of RMDs. Methods: A systematic literature review of app content and development strategies was conducted, followed by patient focus group and an online survey. Based on this information and along with expert opinion, PtC were formulated in a face-to-face meeting by a multidisciplinary task force panel of experts, including two patient research partners. The level of agreement among the panel in regard to each PtC was established by anonymous online voting. Results: Three overarching principles and 10 PtC were formulated. Three PtC are related to patient safety, considered as a critical issue by the panel. Three were related to relevance of the content and functionalities. The requirement for transparency around app development and funding sources, along with involvement of relevant health professionals were also raised. Ease of app access across ages and abilities was highlighted, in addition to considering the cost-benefit of apps from the outset. The level of agreement was from 8.8 to 9.9 out of 10. Conclusion: These EULAR PtC provide guidance on important aspects that should be considered for the development, evaluation and implementation of existing and new apps

Reflections on a contemporary European tragedy

No abstract available

Differential properties of Janus kinase inhibitors in the treatment of immune-mediated inflammatory diseases

Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib

EULAR recommendations for cardiovascular risk management in Rheumatic and Musculoskeletal Diseases, including Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Acknowledgements: The committee wishes to acknowledge the support of the EULAR Standing Committee on Clinical Affairs and the EULAR Secretariat. Funding: This study was funded by European Alliance of Associations for Rheumatology, EULAR. Project number: CLI112Peer reviewedPostprin