DAS28 Score Research Articles

Antibodies against oxidized LDL and atherosclerosis in rheumatoid arthritis patients treated with biological agents: a prospective controlled study.

The aim of this study was to investigate the relation among atherosclerosis, antibodies against oxidized LDL (anti-oxLDL), and inflammation in rheumatoid arthritis (RA) patients treated with biological (b) disease-modifying anti-rheumatic drugs (DMARDs). Fifty-nine patients who were receiving conventional synthetic DMARDs and were eligible for treatment with a biological agent were included in the study. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and IgG antibodies against oxidized LDL (anti-oxLDL) as well as carotid intima-media thickness (cIMT) were determined before and after 6 months of treatment. Thirty-one healthy individuals were used as a control group. At baseline, RA patients had lower TC and HDL-C levels and increased cIMT compared to controls. After a 6-month follow-up, the re-evaluation of carotids revealed a statistically important decrease of cIMT values. This observation was accompanied by a statistically important elevation of HDL-C levels and a reduction of the titer of anti-oxLDL antibodies regardless of the bDMARD that was administered. No statistically significant association was found between the cIMT and anti-oxLDL, HDL-C, CRP, or DAS28 score neither before nor 6 months after treatment using linear regression analyses adjusted for age and gender. We provide evidence that atherogenic lipid profile and ongoing atherosclerosis which characterize RA patients appear to improve after biological therapy, and we also suggest a possible atherogenic effect of IgG anti-ox LDL antibodies.

Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis.

Interstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD. A total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1. Among the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR. Our findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.

Platelet/lymphocyte, neutrophil/lymphocyte, and lymphocyte/monocyte ratios as biomarkers for rheumatoid arthritis: correlation with disease activity

BackgroundAssessment of disease activity in rheumatoid arthritis (RA) patients is essential for the adjustment of therapy. Inflammatory changes in lymphocytes, neutrophils, monocytes, and platelets supported the use of neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) as markers of inflammation, we aimed to explore the clinical significance of PLR, NLR, and LMR in RA patients.ResultsThe study included 120 RA patients and 50 healthy matched controls. Clinical and laboratory data of the patients were assessed. Disease activity was measured using disease activity score (DAS28). Complete blood count (CBC) with differential count was used for the calculation of NLR, PLR, and LMR. Patients had significantly high NLR, and PLR (p < 0.001) and significantly low LMR (p < 0.001) when compared with the control group. Also, there were significant differences in the three ratios between patients in activity and those in remission (p < 0.001). Similarly, there were significant differences in all three ratios between patients with different degrees of disease activity. DAS28 score was positively correlated with NLR, PLR (r = 0.666, p < 0.001, r = 0.586, p < 0.001) and negatively correlated with LMR (r = 0.761, p < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that NLR had the highest sensitivity (86.9%) for RA disease activity, followed by PLR (85.9%) then LMR (76.2%), and regarding the specificity, NLR had high specificity (81%) followed by LMR (78%) then PLR (67%).ConclusionsGiven that NLR, PLR, and LMR were significantly different in patients when compared with the controls, also on comparing different degrees of disease activity and the three ratios were significantly correlated with DAS28 score, in addition to their good sensitivity and specificity for detection of RA disease activity, all this imply that they may be easy, reliable, cost-effective, and time-saving biomarkers when added to DAS28 score for the assessment of RA disease activity.

Relationship Between Vitamin D and Neutrophil-Lymphocyte Ratio with Rheumatoid Arthritis Disease Activity

Introduction: Rheumatoid arthritis is a chronic inflammatory disease characterized by peripheral and symmetrical polyarthritis. Vitamin D deficiency has been linked to the course of several autoimmune diseases, and there is a link. In the process of autoimmune disease, the value of the neutrophil lymphocyte ratio is also known to be one of the parameters to assess the degree of activity. This study was conducted to assess the relationship between neutrophil lymphocyte ratio and rheumatoid arthritis disease activity. Method: This research is a cross-sectional study with a retrospective approach, conducted from January to March 2023. This research was conducted on rheumatoid arthritis sufferers at Haji Adam Malik Hospital, Medan. Subsequent research subjects underwent anamnesis and physical examination to assess the DAS28 score. Blood sampling for examination of the ratio of neutrophil lymphocytes and vitamin D was carried out at Haji Adam Malik Hospital. The data collected was then analyzed using SPSS version 26. Results: There were 67 research subjects with an age range of 43-47 years. The research subjects consisted of 20 men and 47 women. MTX treatment history in the remission group was 56.7%, in the low disease activity group was 80% and in the moderate disease activity group was 81%. Leflunomide treatment history in remission group 43.3%, low disease activity group 20% and moderate disease activity group 19%. Correlation test of vitamin D levels and rheumatoid arthritis disease activity showed a p-value of 0.380. Correlation test of neutrophil lymphocyte ratio and rheumatoid arthritis disease activity showed a p-value of 0.862. Correlation test of vitamin D levels and neutrophil lymphocyte ratio with DAS28 using the Spearman correlation showed­ p-values of 0.133. Conclusion: There was no significant relationship between vitamin D levels and neutrophil lymphocyte ratio with rheumatoid arthritis disease activity (p-value 0.133). Keywords: Vitamin D, Lymphocyte Neutrophil Ratio, DAS28, Rheumatoid Arthritis

PDCD5 as a Potential Biomarker for Improved Prediction of the Incidence and Remission for Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) often involves an altered T-cell subpopulation, higher levels of inflammatory cytokines, and auto-antibodies. This study investigated whether PDCD5 could be a biomarker to predict the incidence and remission of RA so as to guide the therapeutic management of clinical RA. One hundred fifty-two patients (41 being in both active status and stable remission status) who were newly diagnosed with RA and 38 healthy controls were enrolled. Basic clinical data were collected before using blood samples remaining in the clinic after routine complete blood count. The ability of PDCD5 and important indicators to predict the remission of RA was estimated based on receiver operating characteristic curve (ROC) analysis. PDCD5 expression was found to be significantly increased in RA patients in active status in comparison with healthy controls or those in stable remission status. Compared with anti-CCP, ESR and DAS28 score, PDCD5 was of better predictive value with an AUC of 0.846 (95% CI 0.780-0.912) for RA remission. The incidence risk of RA increased with higher levels of PDCD5 (OR = 1.73, 95% CI = 1.45-1.98, P = 0.005) in multiple logistic regression analysis, with the risk increasing by 2.94-times for high-risk group in comparison with low-risk group (OR = 2.94, 95% CI = 2.35-4.62, P < 0.001). The association between PDCD5 and RA remission showed a similar result. For correlation analysis, significant associations were eventually found between PDCD5 and indicated genes (FOXP3, TNF-α, IL-17A, IFN-γ and IL-6) as well as several important clinical parameters including IgG, RF, CRP, ESR, anti-CCP and DAS28 score. This study suggested that increased PDCD5 expression was significantly linked to the incidence and remission of RA. PDCD5 may be used as a novel biomarker for the prediction of RA incidence and remission, especially due to its potential involvement in the development of the condition.

Receptors expressions on peripheral lymphocytes and CD4+ CD183+ as a diagnostics biomarker for rheumatoid arthritis: A case-control study in Ghana.

T cell receptors play important roles in the development and progression of rheumatoid arthritis (RA).Their involvement has been reported in inflammatory autoimmune diseases. However, their role in predicting RA is still under exploration. This study evaluated the expression of CD183 (CXCR3)receptors on T-cells and other relevant biomarkers for detecting RA and determine their relationship with disease activity. This unmatched case-control study included 48 newly diagnosed RA patients and 30 apparent healthy controls from the orthopedic units of Komfo Anokye Teaching Hospital (KATH),Kumasi and Korle-Bu Teaching Hospital (KBTH),Accra, Ghana. Sociodemographic data was obtained, and blood samples were also collected and processed for flow cytometric analysis. Statistical analyses were done using SPSS version 26.0 and R programming language. p < .05 was considered statistically significant. This study found a significant difference in age group (p < .0001), marital status (p = .0210), occupation (p = .0140), educational level (p = .0210) and religion (p = .0100) between RA patients and healthy controls. Moreover, hemoglobin level (p = .0010), waist circumference (p < .0001) and hip circumference (p = .0040) were significantly different between RA patients and controls. RA patients had significantly lower levels of CD4+ CD183+ compared with the control group (p < .001), and was positively correlated with DAS score (r = .0397, p = .789). In Receiver Operator Characteristics analysis, CD4+ CD183+ could significantly detect RA with a high area under the curve (AUC = 0.687, p = .018). At a cut-off of 0.082, CD4+ CD183+ was the best receptor biomarker for detecting RA with a sensitivity of 90.0%, specificity of 25.9%, a positive predictive value of 69.2%, and a negative predictive value of 58.3%. CD4+ CD183+ best predict RA and is positively correlated with disease activity. CD4+ CD183+ could serve as diagnostics and disease-monitoring biomarker for RA; however, it demonstrates low specificity. Future studies should be directed on CD4+ CD183+ and other biomarkers to augment their diagnostics performances and routine management in RA.

Safety and Efficacy of Golimumab in Rheumatoid Arthritis: A Prospective, Multicenter, Real-World Study from India

Abstract Background: Tumor necrosis factor (TNF) has been associated with inflammation and joint destruction in patients with rheumatoid arthritis (RA), and several anti-TNF agents, including golimumab, are currently in clinical use. This postmarketing surveillance (PMS) study was carried out at six rheumatology centers in India to assess the safety and efficacy of golimumab in patients with moderate-to-severe RA, in a real-world setting. Methods: This was a prospective, multicenter, open-label, single-arm, PMS study, where golimumab 50 mg subcutaneous was administered monthly as per locally approved prescribing regulations. The primary endpoint was to assess the safety of golimumab. Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), auto-injector satisfaction/user-friendliness, injection-site pain/reactions, and 28-joint Disease activity score (DAS-28) including erythrocyte sedimentation rate (ESR) (DAS-28-ESR) and C-reactive protein (CRP) (DAS-28 CRP), were evaluated as per investigator’s routine practice. Results: Over 6 months, 120 patients were enrolled and 109 completed the study. Sixty-two (51.7%) patients experienced ≥1 treatment-emergent adverse events (TEAEs). The majority of TEAEs reported in the study were mild to moderate in severity. No deaths were reported. The mean (standard deviation [SD]) change from baseline in HAQ-DI (−0.9 [0.65]) and FACIT-F (14.8 [10.20]) suggested improvement in physical function and fatigue, respectively. The majority of patients (n = 77 [64.2%]) were “very satisfied” on the satisfaction/user-friendliness parameters of auto-injector and majority (n = 99 [91.7%]) did not experience injection-site reactions. Mean (SD) change from baseline of DAS-28 scores (not assessed for all patients; DAS-28 ESR [n = 62]: −2.0 [1.25]) indicated an improvement in disease activity. Conclusions: Golimumab (50 mg) in combination with methotrexate was found to be safe and well-tolerated in Indian patients with moderate-to-severe RA. No new safety signals emerged.

Clinical effects of HBV infection on patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus.

To investigate the clinical effects of HBV infection on patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This is a prospective study. Thirty patients with RA and 30 patients with SLE admitted to Affiliated Hospital of Hebei University from January 2020 to December 2021 with co-infection of HBV were randomly selected and divided into two groups. Both groups were given anti-HBV treatment. An additional 60 patients with a healthy physical examination during the same period were also selected as a control group. The disease activity, immune function and serum inflammatory factor levels were compared between the RA group and the SLE group before and after treatment. After anti-HBV treatment, DAS scores in the RA group and SLEDAI scores in the SLE group were significantly lower than before treatment(P<0.05). The levels of IgG, IgA, IgM and CD8+ in the RA group and the SLE group after treatment were significantly lower than those before treatment. The levels of CCP, RF, ESR and CRP in the RA group before and after treatment were higher than those in the control group(P<0.05). The levels of ESR and CRP in the SLE group before and after treatment were higher than those in the control group, with statistically significant differences(P<0.05). Patients in the RA and SLE groups after HBV infection have an increased degree of inflammatory response in their organism, an altered normal state of immunoglobulin and T-lymphocyte subsets, and a loss of organism immune function, leading to an increase in disease activity.

A study of the association between Galectin-9 gene (LGALS9) polymorphisms and rheumatoid arthritis in Egyptian patients

BackgroundRheumatoid arthritis (RA) is an incessant synovial inflammation of an autoimmune origin, destroying articular cartilages and bones. Galectins are an evolutionarily conserved family of immune-modulatory animal lectins detected in a number of immune cells like T cells, fibroblasts and macrophages. Galectin 9 (Gal-9) has been the subject of many studies for being linked to regulation of both innate and adaptive immune reactions. The objective of the study was to evaluate the link between the Galectin-9 gene (LGALS9) polymorphisms and the susceptibility of RA in Egyptian patients, as well as, detection of the serum level of Gal-9 in RA and its association with LGALS9 polymorphisms, the activity of RA and radiological damage.MethodsA study of 85 participants; group (I): 60 RA cases and group (II): 25 apparently healthy subjects. RA Disease activity index (DAS-28) and Larsen index score were assessed. LGALS9 gene and serum Gal-9 were investigated.Resultsrs4239242 TT genotype and T allele occurred more frequently in RA cases than controls with a significant difference (P = 0.006; P < 0.001 respectively). Gal-9 level was significantly higher among RA cases than control group (P = 0.017). The Gal-9 level showed negative significant correlations with DAS-28 and Larsen score (P < 0.001).ConclusionRA is strongly linked to genetic alterations in the LGALS9 gene and the single nucleotide polymorphism (SNP) rs4239242 TT genotype in the Egyptian population. RA cases in remission or those with low disease activity had higher levels of serum Gal-9 in comparison to cases with moderate and high disease activity and this would be promising in the future of RA treatment.

Diagnostic and Predictive Values of IL-6 in a Group of Iraqi Patients with Rheumatoid Arthritis

Background: Researchers have found that interleukin 6 (IL-6) plays a crucial regulatory function in the onset and progression of a wide range of inflammatory disorders. One of the more prevalent inflammatory illnesses affecting people today is rheumatoid arthritis. Aim of the study: The purpose of this study was to compare the IL-6 levels of rheumatoid arthritis (RA) patients to those of healthy controls and to examine the relationship between IL-6 and RA-related demographic and clinical factors. Materials and Method A total of 80 participants: 40 rheumatoid arthritis (RA) sufferers and 40 healthy controls, all of whom ranged in age from 23 to 61. The serum concentrations of (IL-6) were analyzed using an enzyme-linked immunosorbent assay (ELISA). Results: Increased IL-6 blood levels were associated with rheumatoid arthritis, suggesting that this biomarker may be useful for diagnosing the disease at an early stage. There was no statistically significant correlation between disease severity and the DAS28 score and IL-6 levels in the serum. Conclusion: The cytokine interleukin 6 (IL-6) has been proposed as a biomarker and possible player in the etiology of rheumatoid arthritis.

Serum CDC42 is increased during tumor necrosis factor inhibitor treatment, and its elevation correlates with satisfactory treatment response in rheumatoid arthritis patients.

Our previous study discovered that cell division control protein 42 (CDC42) correlated with decreased disease activity and risk of developing rheumatoid arthritis (RA), along with repressed T helper type 17 cell differentiation. This study aimed to further estimate the longitudinal change of serum CDC42 and its association with treatment outcomes to tumor necrosis factor inhibitor (TNFi) in RA. CDC42 was detected in serum by ELISA at week (W)0, W6, W12, and W24 in 88 RA patients undergoing TNFi treatment, and after enrollment in 20 disease controls (DCs) and 20 healthy controls (HCs). CDC42 was lower in RA patients compared with DCs and HCs (both p < .001); meanwhile, it negatively related to C-reactive protein (p = .011) and DAS28 score (p = .006). Regarding TNFi type, 40.9%, 33.0%, 17.0%, and 9.1% of patients received adalimumab, etanercept, golimumab, and infliximab, respectively. Notably, CDC42 was increased from W0 to W24 in RA patients receiving TNFi treatment (p < .001), also in patients receiving adalimumab (p < .001), etanercept (p < .001), golimumab (p < .001), and infliximab (p = .001). Furthermore, CDC42 at W24 was higher in patients with a clinical response to TNFi treatment compared with those without (p = .023); CDC42 at W12 (p = .027) and W24 (p = .002) was elevated in patients with clinical low disease activity in response to TNFi treatment versus those without; whereas CDC42 at W12 (p = .074) and W24 (p = .068) only showed an increasing trend in patients with clinical remission with TNFi treatment, but did not achieve statistical significance. Circulating CDC42 is elevated during TNFi administration; its increase reflects good 24-week TNFi treatment responses in RA patients.

Neuropathic Pain and Related Factors in Female Patients with Rheumatoid Arthritis

Purpose : Neuropathic pain (Np) can accompany Rheumatoid arthiritis (Ra)like many other diseases. Aim of our study was to investigate the frequency of Np and related factors in female patients with Ra. Methods : Age, disease duration, body mass index (BMI), erythrocyte sedimentation rate (ESR) were recorded. A pain visual analog scale (VAS) was used to record pain intensity and paindetect questionnaire (Pd) was used to record Np score. Ra disease activity was calculated with DAS28 score. Health Assesment Questionnaire (HAQ) was used for functional status. Results : Np scores of the patients were high. A significant correlation was found between Pd and VAS, BMI and HAQ values. The correlation value between Pd and disease duration, age, inflammation, disease activity was not significant Conclusion : All of the patients' pain may not be caused by inflammation. If this is the case, treatment can change. If the pain pattern is questioned and treated, unnecessary use of anti-inflammatory drugs can be prevented.

CCCTC-binding factor: the specific transcription factor of β-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CCCTC-binding factor is the specific transcription factor of β-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.

Psychological assessment using DASS-21 and association of sociodemographic variables with mental health in health-care professionals and general population during COVID-19 pandemic

Background: Millions of people have been impacted by COVID-19 pandemic globally. COVID-19 pandemic has descended people to the realms of uncertainty and isolation which surprisingly are associated with mental distress. Depression, anxiety and stress are one of the prominent psychological factors that might have been significantly impacted by the ongoing pandemic. Aims and Objectives: The present study was conducted predominantly with the aim of assessing psychological impact by COVID-19 in health-care professionals (HCPs) as well as in general population. Materials and Methods: The present study was an observational study conducted in Sher-i-Kashmir Institute of Medical Sciences, Soura, a tertiary level teaching hospital in Union territory of Jammu and Kashmir, India. A total of 250 participants comprising both HCPs and general population were included in the study. Depression, anxiety, stress-scale-21 questionnaire, a validated instrument, was used to assess the depression, anxiety, and stress levels among the participants. Informed consent was taken individually for volunteering in the study and participants were required to fill the questionnaire as per the directed instructions. Results: Out of 250 participants, 54.8%, 68%, and 34.4% were found to have depression, anxiety, and stress, respectively. The prevalence of severe and extremely severe depression corresponded to 9.9% and 6.8% of HCPs, respectively. Severe and extremely severe anxiety existed in 14.9% and 21.1% of HCPs, respectively, followed by 7.5% and 1.2% severe stress and extremely severe stress percentages. About 11.2% and 7.9% participants in community experienced severe and extremely severe depression, respectively. Although 19.1% and 21.3% values corresponded to severe and extremely severe anxiety in community, 5% participants were found to have severe stress, and 4 % had extremely severe stress. A significant positive correlation existed between the levels of depression, anxiety, and stress. No statistically significant association was found between DAS scores and demographic variables except anxiety scores which showed a statistically significant association with HCPs especially nurses, students, and doctors. Conclusion: The findings from this study highlight high prevalence of depression, anxiety and stress experienced during COVID-19 pandemic by all participants. Anxiety in comparison to depression and stress was found to be experienced by majority of participants. Anxiety levels were prominent in nurses, students, and doctors among HCPs.

Physical Function of RA patients Tapering Treatment-A Post Hoc Analysis of the Randomized Controlled RETRO Trial.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.

LAT1 enables T cell activation under inflammatory conditions

The aim of this study was to assess the L-type amino acid transporter-1 (LAT1) as a possible therapeutic target for rheumatoid arthritis (RA). Synovial LAT1 expression in RA was monitored by immunohistochemistry and transcriptomic datasets. The contribution of LAT1 to gene expression and immune synapse formation was assessed by RNA-sequencing and total internal reflection fluorescent (TIRF) microscopy, respectively. Mouse models of RA were used to assess the impact of therapeutic targeting of LAT1. LAT1 was strongly expressed by CD4+ T cells in the synovial membrane of people with active RA and the level of expression correlated with levels of ESR and CRP as well as DAS-28 scores. Deletion of LAT1 in murine CD4+ T cells inhibited the development of experimental arthritis and prevented the differentiation of CD4+ T cells expressing IFN-γ and TNF-α, without affecting regulatory T cells. LAT1 deficient CD4+ T cells demonstrated reduced transcription of genes associated with TCR/CD28 signalling, including Akt1, Akt2, Nfatc2, Nfkb1 and Nfkb2. Functional studies using TIRF microscopy revealed a significant impairment of immune synapse formation with reduced recruitment of CD3ζ and phospho-tyrosine signalling molecules in LAT1 deficient CD4+ T cells from the inflamed joints but not the draining lymph nodes of arthritic mice. Finally, it was shown that a small molecule LAT1 inhibitor, currently undergoing clinical trials in man, was highly effective in treating experimental arthritis in mice. It was concluded that LAT1 plays a critical role in activation of pathogenic T cell subsets under inflammatory conditions and represents a promising new therapeutic target for RA.

Prevalence of periodontitis in patients with rheumatoid arthritis

Background and Aim: Rheumatoid arthritis (RA) patients are more susceptible to the initiation of severe periodontitis which can ultimately intensify their systemic inflammation associated with RA. The present study aimed to determine the incidence of periodontitis in rheumatoid arthritis patients. Materials and Methodology: A cross-sectional analytical study was carried out on 168 rheumatoid arthritis patients in the Department of Dentistry and Internal Medicine of a Tertiary Care Hospital of Lahore, Pakistan from January 2022 to December 2022. All the patients were inquired about their demographic details, medical history and smoking habits. A detailed periodontal examination of full mouth was done and plaque index, clinical attachment level (CAL) and probing pocket depth (PPD) was measured. Rheumatoid factor (RF)’s presence, number of tender and swollen joints, erythrocyte sedimentation rate (ESR); Disease Activity Index (DAS) and hand radiographs were the different RA parameters which were recorded. Periodontal conditions were then associated and correlated with RA parameters. Results: Out of the total 168 RA patients, there were 142 (84.5%) females and 26 (15.5%) male patients. The overall mean age was 48.6 ± 8.64 years. The overall mean DAS score and disease duration was 4.58 ± 1.32 and 9.58 ± 6.8 years respectively.

Multi-omics profiling reveals potential alterations in rheumatoid arthritis with different disease activity levels

BackgroundRheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease, the pathogenesis of which is not clear. Clinical remission, or decreased disease activity, is the aim of treatment for RA. However, our understanding of disease activity is inadequate, and clinical remission rates for RA are generally poor. In this study, we used multi-omics profiling to study potential alterations in rheumatoid arthritis with different disease activity levels.MethodsFecal and plasma samples from 131 rheumatoid arthritis (RA) patients and 50 healthy subjects were collected for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing, and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The PBMCS were also collected for RNA sequencing and whole exome sequencing (WES). The disease groups, based on 28 joints and ESR (DAS28), were divided into DAS28L, DAS28M, and DAS28H groups. Three random forest models were constructed and verified with an external validation cohort of 93 subjects.ResultsOur findings revealed significant alterations in plasma metabolites and gut microbiota in RA patients with different disease activities. Moreover, plasma metabolites, especially lipid metabolites, demonstrated a significant correlation with the DAS28 score and also associations with gut bacteria and fungi. KEGG pathway enrichment analysis of plasma metabolites and RNA sequencing data demonstrated alterations in the lipid metabolic pathway in RA progression. Whole exome sequencing (WES) results have shown that non-synonymous single nucleotide variants (nsSNV) of the HLA-DRB1 and HLA-DRB5 gene locus were associated with the disease activity of RA. Furthermore, we developed a disease classifier based on plasma metabolites and gut microbiota that effectively discriminated RA patients with different disease activity in both the discovery cohort and the external validation cohort.ConclusionOverall, our multi-omics analysis confirmed that RA patients with different disease activity were altered in plasma metabolites, gut microbiota composition, transcript levels, and DNA. Our study identified the relationship between gut microbiota and plasma metabolites and RA disease activity, which may provide a novel therapeutic direction for improving the clinical remission rate of RA.

Can myocardial dysfunction be detected in patients with rheumatoid arthritis with no cardiac symptoms?

The aim of our study was to investigate the role of tissue Doppler and Myocardial Performance Index (MPI) in evaluating cardiac involvement in patients with rheumatoid arthritis (RA) with no cardiac symptoms, to determine whether these measurements differ between healthy controls and RA patients, and whether they can be used to determine the risk of cardiovascular disease and predict prognosis. 50 RA patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA criteria and 50 healthy volunteering controls were included in the study. All patients and controls were assessed using electrocardiography (ECG), echocardiography, conventional Doppler echocardiography and tissue Doppler echocardiography. MPI values were calculated. In addition, RA patients were compared after being divided into two subgroups: seropositive and seronegative RA. Disease activity levels of the patients were determined based on Disease Activity Score in 28 Joints (DAS28). The control group and RA group were compared in terms of PR interval, left atrial diameter, E/A, E/e', and MPI values. Comparisons between the groups yielded statistically significant differences in left atrial diameter, E/A, E/e', and MPI values and no significant difference in PR intervals. These parameters were also compared between seropositive and seronegative patients. Left atrial diameter was significantly higher in seronegative patients than in seropositive patients. There was no significant difference in the other values. DAS28 scores had no correlation with cardiac parameters. Early detection of ventricular dysfunction in RA may be useful in clinical practice when predicting prognosis and optimizing treatment. The present study found that RA patients had impaired tissue Doppler measurements and MPI results compared to controls. MPI and tissue Doppler may be useful in early detection of ventricular dysfunction.

Benefit of Multiple IncobotulinumtoxinA Injections for Pain Reduction in Adult Patients with Limb Spasticity: an Analysis of Pooled Data from Phase 2 and 3 Studies (P12-11.009)

<h3>Objective:</h3> To assess pain relief after multiple incobotulinumtoxinA (incoA) injections in a large sample of patients (pts) with limb spasticity-associated pain (SAP) using pooled data from six phase 2/3 studies (four placebo-controlled). <h3>Background:</h3> Repeated treatment with incoA has shown pain-relieving benefits in pts with limb spasticity in individual studies. <h3>Design/Methods:</h3> Adults with upper limb SAP received up to 4 incoA injections (total dose ≤400U) administered at 12- to 14-week intervals (injection cycles [ICs] 1–4; total observation period up to 56 weeks). Only IC 1 was placebo-controlled. Pain severity was assessed at control visits (CVs; 4 weeks after each injection) using the Disability Assessment Scale (DAS; pain scores ranging from 0 [no pain] to 3 [severe pain]). The proportions of pts with a response (defined as a reduction by ≥1 point in the DAS score from baseline to each CV) and with a complete response (DAS pain score=0) were assessed at every CV. Data were descriptively analyzed. As placebo-treated pts in IC 1 received incoA in subsequent cycles, they contributed data to the appropriate incoA CVs 1–4. <h3>Results:</h3> 515 pts with SAP at baseline were included in this analysis (515, 297, 263, and 181 pts at CVs 1–4, respectively). Response rates increased over time, being 53.0%, 63.3%, 66.9%, and 72.4% at CVs 1–4, respectively. Likewise, the proportion of pts with complete response increased over time, being 27.6%, 38.4%, 39.5%, and 43.6% at CVs 1–4, respectively. <h3>Conclusions:</h3> In pts with upper limb SAP, treatment response rates were sustained and showed a cumulative effect over 56 weeks after multiple incoA injections, with a complete pain relief in &gt;40.0% of pts. Results support the use of incoA in reducing upper limb SAP in affected adults. <b>Disclosure:</b> Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merz. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merz. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ipsen. Jorg Wissel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Dr. Camoes-Barbosa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MERZ, ABBVIE, IPSEN. Dr. Camoes-Barbosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MERZ, ABBVIE, IPSEN. Mr. Comes has received personal compensation for serving as an employee of Merz Pharmaceuticals GmbH. Michael Althaus has received personal compensation for serving as an employee of Merz Pharmaceuticals. Astrid Scheschonka has received personal compensation for serving as an employee of Merz Therapeutics. Dr. Simpson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Simpson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz.