ObjectivesTo compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs).MethodsPatients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models.ResultsOf the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most ‘stringent’ outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%).ConclusionThe ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally ‘captured’ patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.
Introduction: The aim of this study was to conduct a systematic review in order to examine the effectiveness of ozone therapy on knee osteoarthritis. The objectives were to evaluate the effect over time of ozone therapy in terms of knee pain, functional improvement and radiographic progression.Material and Methods: A search was carried out on PubMed, Embase, Cochrane Library, Scopus and Web of Science databases to identify randomized and controlled studies focusing on this association. The following descriptors were used in English: ozone therapy, knee osteoarthritis. A descriptive summary and quality assessment was made of all studies included for analysis.Results: Six randomized and controlled studies were identified. The risk of bias assessment demonstrated that one study was considered as having a moderate risk of bias and the remainder a high risk of bias. No quantitative analysis of the data was performed, as the studies included were not sufficiently homogeneous. The participants in the studies were generally elderly patients with mild to moderate knee osteoarthritis.Discussion: The variability of ozone therapy and the comparators demonstrates that there is no standardized therapy. Few studies reported adverse effects, and where they occurred, they were mild and associated with the procedure.Conclusion: Ozone therapy proved effective in the short-term in relation to placebo and when combined with hyaluronic acid, but it was not superior to other current treatments. More randomised and controlled studies are needed to evaluate the risks/benefits of ozone therapy, both in the short term and the medium/long term.
CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.
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