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Objective: The persistence of biologic (b) and targeted synthetic (ts) disease‐modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real‐life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. Methods: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. Results: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00–2.50; p =.049), PsA (HR 2.48; 95% CI 1.65–3.72) and AS (HR 16.77; 95% CI 7.37–38.16; p <.001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05–1.21). Conclusions: In this real‐life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients. [ABSTRACT FROM AUTHOR]

Introduction: Tocilizumab (TCZ) treatment is associated with dyslipidaemia, including a rise in triglycerides through a mechanism poorly understood. Three molecules play key roles in the regulation of triglyceride metabolism: apolipoprotein C‐III (ApoC‐III), angiopoietin‐like protein 4(ANGPLT4) and lipoprotein lipase (LPL). The aim of this work was to analyse whether the changes in triglycerides shown by TCZ‐treated RA patients could stem from the dysregulation that can occur in these regulatory molecules. Methods: Twenty‐seven RA patients included in the TOCRIVAR study who received TCZ (8 mg/kg IV/q4w) were evaluated at baseline and at Weeks 12, 24 and 52 of treatment. ANGPTL4, ApoC‐III and LPL, a complete lipid profile and RA disease activity, were analysed at baseline and at each visit. Multivariable linear mixed models were performed to study changes over time in lipids and regulatory molecules. Results: After 24 weeks of TCZ treatment, HDL cholesterol, apolipoprotein A1 and triglycerides increased, whereas lipoprotein (a) decreased significantly from baseline values. However, 1 year after TCZ, no significant differences in lipid pattern were observed with respect to baseline. Serum ANGPTL4 and Apo‐CIII levels decreased gradually over time, both being significantly lower than baseline values at Week 52. LPL concentration did not change significantly during TCZ treatment. Remarkably, the elevation of triglycerides at Week 24 maintained its statistical significance after adjusting for the changes in ApoC‐III, ANGPTL4 and LPL. Conclusion: In TCZ‐treated RA patients basal serum levels of ANGPLT4 and ApoC‐III, but not LPL, decreased significantly. However, the elevation of triglycerides after TCZ was not related to changes in these regulatory molecules. [ABSTRACT FROM AUTHOR]

Aim: To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors. Methods: Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). Results: Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0–73.9) at year 1% and 37.7% (95% CI: 33.3–42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first‐line therapy (hazard ratio [HR] for discontinuation 1.52 for second‐ and 1.79 for third/later‐line vs. first‐line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation. Conclusion: Based on this retrospective analysis of the BIOBADASER registry, nearly two‐fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare physical activity (PA) in a group of patients with psoriatic arthritis (PsA) versus healthy controls and to determine whether the mobility of these patients is affected by disease activity.Methods: A group of 52 patients with PsA and 53 controls were included in this case-control study. PA was assessed by accelerometry in both groups and additionally with the International Physical Activity Questionnaire (IPAQ) in patients with PsA. Multiple regression analysis was used to compare PA between groups and to determine the relationship between PA and PsA features, including disease activity, as assessed by the 28-joint Disease Activity Score (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA) score. In a group of 36 patients, a test-retest study was carried out after 6 months.Results: The time engaged in moderate-to-vigorous physical activity (MVPA) per day, as evaluated by accelerometry, and adjusted by confounders, proved similar in patients with PsA and controls. In patients with PsA, disease activity was inversely related to PA as assessed either by IPAQ or accelerometry. When PA was compared in patients with PsA between the 2 visits, a significant difference in the amount of time doing MVPA was found (42 ± 33 versus 30 ± 22 minutes/day; P = 0.004). Interestingly, in the test-retest study, variations in disease activity over time based on DAPSA scores (r = -0.49, P = 0.002) and DAS28 using the C-reactive protein level (r = -0.4, P = 0.017) were inversely correlated with changes in PA, as determined by accelerometry.Conclusion: Patients with PsA show levels of PA like healthy controls. In patients with PsA, disease activity and PA are inversely correlated and the evaluation of PA by accelerometry is sensitive to changes in disease activity. [ABSTRACT FROM AUTHOR]

Objective: Cholesterol efflux capacity (CEC) is the ability of high‐density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages. Lipid profiles and CEC appear to be altered in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) due to disease activity and inflammation. CEC has been linked to cardiovascular events in the general population and to subclinical atherosclerosis in SLE and RA patients. The aim of this study was to establish whether CEC varies between patients with SLE and those with RA. Methods: The study encompassed 460 individuals (195 SLE patients and 265 patients with RA). CEC (using an in vitro assay) and concentrations of lipoprotein serum were assessed in both populations. A multivariable regression analysis was performed to study whether CEC differs between SLE patients and RA patients. Results: Comparison of lipid patterns revealed that patients with RA have lower HDL cholesterol and higher apolipoprotein B serum levels than SLE patients. CEC was downregulated in SLE patients compared to patients with RA (β –12 [95% confidence interval –13, –10], P < 0.001). It occurred independently of traditional cardiovascular risk factors, statin use, disease‐related data, and other variations in the lipid profile related to the diseases. Conclusion: Patients with RA have a more proatherogenic lipid pattern compared to those with SLE. However, CEC seems to be more damaged in SLE patients than in RA patients. [ABSTRACT FROM AUTHOR]

Neutrophils destroy invading microorganisms by phagocytosis by bringing them into contact with bactericidal substances, among which ROS are the most important. However, ROS also function as important physiological regulators of cellular signaling pathways. Here, we addressed the involvement of oxygen derivatives in the regulation of human neutrophil rolling, an essential component of the inflammatory response. Flow experiments using dihydroethidium‐preloaded human neutrophils showed that these cells initiate an early production of intracellular ROS during the rolling phase of the adhesion cascade, a phenomenon that required cell rolling, and the interaction of the chemokine receptor CXCR2 with their ligand CXCL8. Flow cytometry experiments demonstrated that L‐selectin shedding in neutrophils is triggered by ROS through an autocrine–paracrine mechanism. Preincubation of neutrophils with the NADPH oxidase complex inhibitor diphenyleniodonium chloride significantly increased the number of rolling neutrophils on endothelial cells. Interestingly, the same effect was observed when CXCL8 signaling was interfered using either a blocking monoclonal antibody or an inhibitor of its receptor. These findings indicate that, in response to CXCL8, neutrophils initiate ROS production during the rolling phase of the inflammatory response. This very early ROS production might participate in the modulation of the inflammatory response by inducing L‐selectin shedding in neutrophils. We propose that activation of the NADPH oxidase complex by CXCL8 releases superoxide anions to the extracellular milieu. This superoxide generates an oxidative attack on the prodomain thiol group of ADAM‐17, which is activated and process the extracellular domain of L‐selectin, causing its release from the cell membrane. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) comprise a heterogeneous group of pharmacological agents used for the symptomatic treatment of fever, pain, and inflammation. Although the main mechanism of action of NSAIDs consists of inhibiting prostaglandin synthesis by blocking the enzyme cyclooxygenase (COX), clinical, and experimental data strongly indicate the existence of additional mechanisms. Some of the COX-independent effects are related to the ability of NSAIDs to penetrate biological membranes and disrupt important molecular interactions necessary for a wide array of cellular functions, including cell adhesion. These effects, in particular those that interfere with l-selectin function in neutrophils during the inflammatory response, may contribute to the anti-inflammatory properties that NSAIDs exert in vivo. Recent contributions in this field have shown that the anti- l-selectin effect of NSAIDs is related to the NADPH-oxidase-dependent generation of superoxide anion at the plasma membrane. These findings might represent a novel approach for developing new and effective anti-inflammatory compounds with a better safety profile than the currently available NSAIDs. [ABSTRACT FROM AUTHOR]