European Headache Federation recommendations for placebo and nocebo terminology

Background and aim Despite recent publications, practitioners remain unfamiliar with the current terminology related to the placebo and nocebo phenomena observed in clinical trials and practice, nor with the factors that modulate them. To cover the gap, the European Headache Federation appointed a panel of experts to clarify the terms associated with the use of placebo in clinical trials. Methods The working group identified relevant questions and agreed upon recommendations. Because no data were required to ans

Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: Review of randomised controlled trials could point towards a paradigm shift

Treatment of rheumatoid arthritis (RA) has improved substantially during the last decades, mainly due to the development and introduction in everyday practice of new, highly efficacious, disease-modifying antirheumatic drugs (DMARDs), more optimal usage of them, earlier diagnosis and tighter control of disease activity targeting at remission. Methotrexate is still today the anchor drug and the first-line treatment after diagnosis. However, numerous studies comparing methotrexate and biologic DMARDs, as well as new targeted synthetic DMARDs, both in early as in more established disease, have shown consistently better efficacy of the latter compared with methotrexate, with methotrexate yielding remission to maximum half of patients. This could suggest a new paradigm shift with earlier start of a biologic or a targeted synthetic DMARD, with the possibility of subsequent discontinuation in case of achievement of stable remission. Several strategy trials, however, have shown that there might be a clinical and structural benefit of initial, aggressive therapy, possibly even associated with higher chance of remaining in remission, after cessation of the biologic DMARD and continuing with methotrexate alone, but they have failed to show a clear advantage of such an aggressive treatment strategy. This might become a valuable option for the future treatment algorithm of RA, especially for a subgroup of patients with RA, but further confirmation from future research is needed. The crucial role of glucocorticoid use as part of the combination strategy should be acknowledged, and strategy trials should include this combination as an active comparator. © 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: Review of randomised controlled trials could point towards a paradigm shift

Treatment of rheumatoid arthritis (RA) has improved substantially during the last decades, mainly due to the development and introduction in everyday practice of new, highly efficacious, disease-modifying antirheumatic drugs (DMARDs), more optimal usage of them, earlier diagnosis and tighter control of disease activity targeting at remission. Methotrexate is still today the anchor drug and the first-line treatment after diagnosis. However, numerous studies comparing methotrexate and biologic DMARDs, as well as new targeted synthetic DMARDs, both in early as in more established disease, have shown consistently better efficacy of the latter compared with methotrexate, with methotrexate yielding remission to maximum half of patients. This could suggest a new paradigm shift with earlier start of a biologic or a targeted synthetic DMARD, with the possibility of subsequent discontinuation in case of achievement of stable remission. Several strategy trials, however, have shown that there might be a clinical and structural benefit of initial, aggressive therapy, possibly even associated with higher chance of remaining in remission, after cessation of the biologic DMARD and continuing with methotrexate alone, but they have failed to show a clear advantage of such an aggressive treatment strategy. This might become a valuable option for the future treatment algorithm of RA, especially for a subgroup of patients with RA, but further confirmation from future research is needed. The crucial role of glucocorticoid use as part of the combination strategy should be acknowledged, and strategy trials should include this combination as an active comparator. © 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Cadherin-11 as a therapeutic target in chronic, inflammatory rheumatic diseases

Cadherin-11 has been identified as a key regulator of synovial architecture mediating contact between Fibroblast-like Synoviocytes and organization in the lining layer. A central role for cadherin-11 has also been suggested in the formation of the rheumatoid pannus. Therapeutic targeting of cadherin-11 results in amelioration of autoimmune experimental arthritis, as well as of experimental fibrosis. In addition, cadherin-11 expression is upregulated in the synovium of patients with chronic inflammatory arthritis, whereas detection of cadherin-11 mRNA transcripts in the peripheral blood has been associated with more severe disease phenotypes in two prototypic conditions of chronic joint inflammation and fibrosis, namely, rheumatoid arthritis and systemic sclerosis, respectively. Currently, a monoclonal antibody against cadherin-11 is in early phases of clinical trials in patients with rheumatoid arthritis. Herein, we review the current knowledge regarding the potential role of cadherin-11 in pathogenesis, as well as a biomarker and therapeutic target in chronic inflammatory rheumatic diseases. © 2017 Elsevier Inc

Accelerated atheromatosis and arteriosclerosis in primary systemic vasculitides: Current evidence and future perspectives

Purpose of review Primary systemic vasculitides (PSV) encompass a subset of autoimmune diseases, characterized by inflammation of blood vessels. Atheromatosis and arteriosclerosis may be accelerated in several PSV and account for the increased rate of cardiovascular morbidity that some exhibit. We aimed to summarize recent studies reporting on the acceleration of atheromatosis and/or arteriosclerosis in each type of PSV, using state-of-the-art noninvasive vascular biomarkers with clinical value as end points. Recent findings Limited number of PSV patients and methodology limitations reduce the value of many published studies. Accelerated atheromatosis, as measured by the use of carotid ultrasonagraphy (plaques and intimal-medial thickening) and increased arterial stiffening, as measured by the use of applanation tonometry (carotid to femoral pulse wave velocity), are currenly well established in Takayasu arteritis, Kawasaki disease and Behcet's disease. The association of atheromatosis and arteriosclerosis with polyarteritis nodosa and small vessel vasculitides remains less established and studied, so far. Summary Accelerated atheromatosis and arteriosclerosis or arteriosclerosis are established in some PSV. The potential clinical value of easy-to-measure and clinically useful noninvasive vascular biomarkes prompts the need for large prospective cohorts in order to provide useful future guidance regarding the prognosis and treatment of PSV patients. © Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved

The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases

Importance: TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases. Objectives: This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA). Methods: An extensive literature search was performed in the PubMed database using the following keywords: TL1A, death receptor 3, DR3, decoy receptor 3, DcR3, TNFSF15, TNFRSF25, and TNFSF6B. Studies were assessed and selected in view of their relevance to autoimmune rheumatic diseases. Conclusion: The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of a variety of autoimmune rheumatic diseases. These molecules may be promising therapeutic targets for inflammatory arthritis. © 2015 Elsevier Inc