Adipokines may have aggravating, although may be minor, structural effects in early-stage knee OA.
The results indicate that the administration of infliximab after or simultaneously with leflunomide is safe and efficacious in RA patients.
IntroductionSystemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure.Methods and analysisThe UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years.Ethics and disseminationThe study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels.Trial registration numbersNCT04464434; NL 8720.
BackgroundIt is hypothesized that patients with knee osteoarthritis (OA) can be classified into different phenotypes. Knowledge of these phenotypes may contribute to developing effective targeted treatment strategies.ObjectivesTo identify different longitudinal phenotypes of knee OA using biochemical markers and to compare these phenotypes with regard to radiographic joint space loss (JSL) and/or pain progression.MethodsBaseline, 1-year, and 2-year biochemical marker data from the FNIH OA Biomarker Consortium were used. This consortium is a nested case-control study of 600 subjects with one symptomatic index knee showing radiographic OA changes of Kellgren and Lawrence grade 1 to 31. Subjects were classified as either JSL progressors, pain progressors, JSL+pain progressors, or non-progressors according to predefined criteria (pain progression=persistent increase in WOMAC pain≥9 points (0–100 scale) from baseline to 2, 3 or 4 years, JSL progression=decrease in JSW≥0.7mm from baseline to 2, 3 or 4 years).Biochemical markers included in the current analysis were sCTX-I, uαCTX-I, uβCTX-I, sNTX-I, uCTX-II, sCPII, sC2C, sC1,2C, sColl2–1 NO2, sCOMP, sHA, and sMMP (u=urinary, s=serum). First, using principal component analysis (PCA), the individual markers were reduced into a number of clusters of markers (components) that may represent common underlying domains. Second, a hierarchical cluster analysis (HCA) was performed to differentiate between longitudinal courses (phenotypes) of these marker clusters. The optimum number was determined from the additive value of each newly identified phenotype as compared to already identified phenotypes. Third, these longitudinal phenotypes were compared with regard to percentages of patients in each of the JSL and/or pain progression categories.ResultsPCA showed an optimal solution of three components. Looking at the markers that loaded maximally onto each of the components, they were interpreted as cluster of bone (sCTX-I, uαCTX-I, uβCTX-I, sNTX-I, uCTX-II), cartilage (sCPII, sC2C, sC1,2C, sColl2–1 NO2), and synovial (sCOMP, sHA, and sMMP) metabolism, respectively. HCA revealed an optimum of seven longitudinal phenotypes. Based on the relative predominance of the component(s) throughout follow-up, phenotypes were named “high bone”, “high cartilage”, “high synovium”, “low cartilage”, “low synovium”, “low bone, cartilage and synovium” and “low bone and high synovium” phenotype, respectively (Figure 1, dendrogram and heatmap). Phenotypes differed with regard to percentages of patients in JSL and/or pain progression categories (Figure 1, pie charts) as well as other demographic, clinical, and radiographic parameters (data not shown).ConclusionsSeven longitudinal phenotypes of knee OA could be identified based on biochemical markers representing bone, cartilage and synovial metabolism. These phenotypes showed relevant differences in other characteristics, such as JSL and/or pain progression.References Kraus VB, Collins JE, Hargrove D, et al. Predictive validity of biochemical biomarkers ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.