Spondyloarthritis is a group of immune-mediated rheumatic disorders that significantly impact patients' physical function and quality of life. Patients with spondyloarthritis experience a greater ...prevalence of cardiometabolic disorders, such as obesity, hypertension, dyslipidemia and diabetes mellitus, and these comorbidities are associated with increased spondyloarthritis disease activity and risk of cardiovascular events. This narrative review summarizes the evidence for a physiological link between inflammatory status and cardiometabolic comorbidities in spondyloarthritis, as well as the impact of interleukin (IL)-17 blockade versus other molecular mechanisms in patients with cardiometabolic conditions. The IL-23/IL-17 axis plays a pivotal role in the pathophysiology of spondyloarthritis by promoting inflammation and tissue remodeling at the affected joints and entheses. The importance of the IL-23/IL-17 signaling cascade in underlying sub-clinical inflammation in common cardiometabolic disorders suggests the existence of shared pathways between these processes and spondyloarthritis pathophysiology. Thus, a bidirectional relationship exists between the effects of biologic drugs and patients' cardiometabolic profile, which must be considered during treatment decision making. Biologic therapy may induce changes in patients' cardiometabolic status and cardiometabolic conditions may conversely impact the clinical response to biologic therapy. Available evidence regarding the impact of IL-17 blockade with secukinumab on cardiometabolic parameters suggests this drug does not interfere with traditional cardiovascular risk markers and could be associated with a decreased risk of cardiovascular events. Additionally, the efficacy and retention rates of secukinumab do not appear to be negatively affected by obesity, with some studies reporting a positive impact on clinical outcomes, contrary to that described with other approaches, such as tumor necrosis factor blockade. In this article, we also review evidence for this bidirectional association with other treatments for spondyloarthritis. Current evidence suggests that IL-17-targeted therapy with secukinumab is highly effective in spondyloarthritis patients with cardiometabolic comorbidities and may provide additional cardiometabolic benefits.
Rheumatoid arthritis (RA) occurs more frequently in women than in men, and the studies that have addressed clinical and prognostic differences between the sexes are scarce and have contradictory ...results and methodological problems. The present work aims to evaluate sex- and gender-related differences in the clinical expression and prognosis of RA as well as on the impact on psychosocial variables, coping behavior, and healthcare use and access. By identifying between sex differences and gender-related outcomes in RA, it may be possible to design tailored therapeutic strategies that consider the differences and unmet needs. Being that sex, together with age, is the most relevant biomarker and health determinant, a so-called personalized medicine approach to RA must include clear guidance on what to do in case of differences.
Introduction
Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences ...between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS).
Materials and methods
Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry.
Results
We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE (p < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups (p < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p < 0.001). SLE-APS patients showed higher mortality rates (p < 0.001).
Conclusions
SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.
Objectives:
We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting.
...Methods:
This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values.
Results:
We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of discontinuation were male gender (HR 0.54, 95% CI 0.38-0.78
p
= 0.001), obesity (HR 0.53, 95% CI 0.30-0.93
p
= 0.027), hypertension (HR 0.55, 95% CI 0.30-0.93
p
= 0.008), and diabetes (HR 0.42 95% CI 0.18-0.99
p
= 0.047) while number of previous biologics and depression were predictors of discontinuation (HR 1.18, 95% CI 1.04-1.34
p
= 0.011 and HR 2.53, 95% CI 1.61-3.96
p
< 0.001).
Conclusions:
SEC showed a good retention rate in a population previously exposed to several biological therapies. As a novelty, cardiometabolic comorbidities were associated with better drug survival.
The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by ...1-methyl-3'-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV.
The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare ...practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and provide data supporting their functionality. The first mRNA, called RBD-mRNA, encodes a trimeric form of the virus spike protein receptor binding domain (RBD). The other mRNA, termed T-mRNA, codes for the relevant HLA I and II spike epitopes. The two mRNAs (COVARNA mRNAs) were designed to be used for delivery to cells in combination, with the RBD-mRNA being the primary source of antigen and the T-mRNA working as an enhancer of immunogenicity by supporting CD4 and CD8 T-cell activation. This innovative approach substantially differs from other available mRNA vaccines, which are largely directed to antibody production by the entire spike protein. In this study, we first show that both mRNAs are functionally transfected into human antigen-presenting cells (APCs). We obtained peripheral blood mononuclear cell (PBMC) samples from three groups of voluntary donors differing in their immunity against SARS-CoV-2: non-infected (naïve), infected-recovered (convalescent), and vaccinated. Using an established method of co-culturing autologous human dendritic cells (hDCs) with T-cells, we detected proliferation and cytokine secretion, thus demonstrating the ability of the COVARNA mRNAs to activate T-cells in an antigen-specific way. Interestingly, important differences in the intensity of the response between the infected-recovered (convalescent) and vaccinated donors were observed, with the levels of T-cell proliferation and cytokine secretion (IFNγ, IL-2R, and IL-13) being higher in the vaccinated group. In summary, our data support the further study of these mRNAs as a combined approach for future use as a vaccine.
IntroductionThe nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in ...this regard are yet to be assessed.MethodsStudy including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.ResultsAfter a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: −1.2 (95% CI: −0.3 to −0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high–very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.ConclusionInflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
Phagocyte function deregulated in age‐restricted inflammatory disorders.
This study was conducted to evaluate phagocyte function in patients with age‐related chronic inflammatory conditions. It ...included 95 patients with PMR, 17 with GCA, 40 with EORA, and 25 age‐matched HCs. Serum IL‐8 was determined with a bead array. The chemotactic capacity, phagocytic ability, and oxidative burst activity of circulating leukocytes were determined with flow cytometry kits. Patients with active chronic inflammatory diseases showed a significant increase in circulating levels of IL‐8 that remained elevated in patients with PMR or EORA, despite treatment. No correlation was found between circulating IL‐8 and the migratoty capacity of neutrophils. Neutrophils from patients with active EORA without stimulus and after fMLP stimuli showed a higher capacity to migrate than those of the HCs (P=0.033). The phagocytic activity of granulocytes in the patients with GCA was significantly higher than in the HCs and the patients with PMR or EORA (P<0.05). The percentage and MFI of phagocytes that produce ROIs when stimulated with Escherichia coli was significantly reduced in neutrophils and monocytes from the patients with age‐restricted inflammatory conditions. We concluded that the effector functions of phagocytes, determined to be chemotaxis, phagocytosis, and oxidative burst, are deregulated in age‐restricted inflammatory disorders and may have a pathogenic role.
Abstract
Objectives
The Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance ...in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA.
Methods
This was a cross-sectional observational study that included 90 consecutive patients with PsA. The measurement properties of ASAS-HI were analysed against the Disease Activity index for PSoriatic Arthritis (DAPSA) and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A multivariate analysis was performed to weigh the ASAS-HI items associated with DAPSA active disease and PsAID high impact.
Results
Mean ASAS-HI was 5.8 (4.3). Convergent validity was high both against DAPSA (ρ 0.78, P < 0.0001) and PsAID (ρ 0.80, P < 0.0001). ASAS-HI showed a high discriminant capacity for both DAPSA remission optimal criterion ≤ 2, area under the receiver operating characteristic curve (AUC) 0.92 (95% CI: 0.85, 0.97), P < 0.0001, and low activity optimal criterion ≤6, AUC 0.87 (95% CI: 0.79, 0.94), P < 0.0001. The ASAS-HI items significantly associated with DAPSA active disease were: ‘I find it hard to stand for long’ (β 4.48, P < 0.0001), ‘I find it hard to concentrate’ (β 2.94, P = 0.042) and ‘I sleep badly at night’ (β 1.86, P = 0.044). As for PsAID, the only item significantly associated with a high impact was ‘I sleep badly at night’ (β −3.29, P = 0.015).
Conclusion
We demonstrated construct validity of ASAS-HI, a spondyloarthritis instrument, for the assessment of global health in patients with PsA.
Objective
To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first‐line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to ...Behçet's disease (BD).
Methods
We conducted an open‐label multicenter study of IFX versus ADA for BD‐related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first‐line biologic agent based on physician and patient agreement. Patients received 3–5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4–8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups.
Results
The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best‐corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042).
Conclusion
Although both IFX and ADA are efficacious in refractory BD‐related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow‐up.
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