A high prevalence of periodontitis has been reported in rheumatoid arthritis (RA) patients, although the strength of this association, its temporal link and the possible relationship between the ...severity of periodontitis and RA disease activity remain unclear. The objective of this work was to investigate whether periodontitis is associated with RA and whether periodontitis severity is linked to RA disease activity.
This case-control study included 187 patients diagnosed with RA and 157 control patients without inflammatory joint disease. RA disease activity and severity were evaluated by the Disease Activity Score 28, the Simplified Disease Activity Index, the Clinical Disease Activity Index, rheumatoid factor, anti-citrullinated protein antibody titers, the erythrocyte sedimentation rate, C-reactive protein, presence of extra-articular manifestations and type of RA therapy. Exposure severity was assessed by the following periodontal parameters: plaque index, bleeding on probing, probing pocket depth and clinical attachment levels. Sociodemographic variables and comorbidities were evaluated as confounding variables. Outcome and exposure variables were compared by both parametric and nonparametric tests, and possible associations were assessed through regression analysis with a calculation for the adjusted odds ratio (OR).
A significant association was demonstrated between periodontitis and RA with an adjusted OR of 20.57 (95% CI 6.02-70.27, p < 0.001). Compared with controls, all parameters related to periodontal status (plaque index, bleeding on probing, probing pocket depth and clinical attachment levels) were significantly worse in RA patients (p < 0.001). Periodontitis severity was significantly associated with RA disease activity (p < 0.001), showing in an ordinal logistic regression model an association between periodontal severity and disease activity with an adjusted OR of 2.66 (95% CI 1.24-5.74, p = 0.012).
A significant association was demonstrated between periodontitis and RA, independent of other confounders. This association was more evident in patients with pronounced periodontal disease and higher RA disease activity.
The aim of this study was to evaluate the association between periodontal parameters related with the periodontal disease severity and the presence and levels of anti-citrullinated protein antibodies ...(ACPAs) in rheumatoid arthritis (RA) patients.
This cross-sectional study included 164 RA patients. Socio-demographics and RA disease characteristics, including ELISA-detected ACPA (anti-CCP-2), were recorded. Exposure was assessed by periodontal parameters: plaque index (PI), bleeding on probing (BoP), probing pocket depth, and clinical attachment levels (CAL). Presence and levels of ACPAs (outcome) and exposure variables were compared by both parametric and non-parametric tests and associations were evaluated by adjusted odds ratio (OR).
A significant association was observed between the presence of anti-CCP antibodies and severity of periodontal outcomes such as the mean CAL (OR 1.483, p = 0.036), mean PI (OR 1.029, p = 0.012), and the number of pockets ≥ 5 mm (OR 1.021, p = 0.08). High anti-CCP antibodies levels were associated with mean CAL, mean PI, and number of pockets ≥ 5 mm with an OR of 1.593 (p = 0.043), 1.060 (p < 0.001), and 1.031 (p = 0.031), respectively. Furthermore, a significant increase of 4.45 U/mL in anti-CCP antibodies levels (p = 0.002) in RA patients was found for each pocket ≥ 5 mm after adjusting for age, gender, smoking, time of disease evolution, and RA activity.
In RA patients, the severity of periodontal conditions such as mean CAL, mean PI, and the number of pockets ≥ 5 mm were linearly associated with both the presence and levels of anti-CCP antibodies.
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.
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.
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.
The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use ...patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007-2009; 2010-2013; 2014-2017; 2018-2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p < 0.001), disease activity (p < 0.001), retention rate (p < 0.001) and the use of tumor necrosis factor inhibitors as a first-line treatment (p < 0.001) showed a significant tendency to decrease. Conversely, comorbidities, as assessed by the Charlson index (p < 0.001), and the percentage of patients using bDMARDs in monotherapy (p < 0.001), and corticosteroids (p < 0.001) tended to increase over time. Over the entire period of the study's analysis, 3289 patients started a second biologic. The following trends were observed: decreased DAS28 at switching (p < 0.001), lower retention rates (p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p < 0.001). From 2007 until now rheumatic patients who started a biologic were older, exhibited less clinical activity, presented more comorbidities, and switched to a different biologic more frequently and earlier.
Objective
Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention ...rates during 24 months of follow‐up among patients with PsA initiating their first TNFi.
Methods
Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease‐modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan–Meier estimator.
Results
We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28‐CRP (women vs men, 4.4 SD 1.2 vs 4.2 SD 1.2), though patient‐reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk RR 0.82; 95% confidence interval CI 0.80–0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81–0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively).
Conclusion
Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.
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.
B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the ...inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors.
Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20
mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines.
B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF.
These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium.
Background & Aims
In cirrhosis, the reliability of formulas that estimate renal function, either those specifically developed in this population or the classic equations, has not been properly ...quantified. We studied the agreement between estimated (eGFR) and measured glomerular filtration rate (mGFR) in cirrhosis.
Methods
Renal function was estimated with 56 formulas including specific equations: Glomerular Filtration Rate Assessment in Liver Disease (GRAIL), Royal Free Hospital Cirrhosis (RFHC) and Mindikoglu‐eGFR, and measured with a gold standard procedure; plasma clearance of iohexol using dried blood spots sampling in a group of cirrhotics. The agreement eGFR‐mGFR was evaluated with specific tests: total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). We defined acceptable agreement as values: TDI < 10%, CCC ≥ 0.9 and CP > 90%.
Results
A total of 146 patients (age 65 ± 9 years, 81% male) were evaluated; 61 (42%) Child A, 67 (46%) Child B and 18 (12%) Child C. Median MELD‐Na was 14 (9‐15). The agreement between eGFR and mGFR was poor: TDI averaged was of 73% (90% of the estimations ranged from ±73% of mGFR); CCC averaged was 0.7 indicating low concordance and CP averaged 22% indicating that 78% of the estimations have an error > 10%. Specific formulas showed also poor agreement: TDI was 82%, 70% and 37% for the GRAIL, RFHC and Mindikoglu equations, respectively.
Conclusions
Overall, formulas poorly estimated renal function in cirrhotic patients. Specific formulas designed for cirrhosis did not outperform classic equations. eGFR must be considered with caution in cirrhotic patients.
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