Rheumatoid Arthritis Disease Activity Research Articles

Association between dietary inflammatory index scores and the increased disease activity of rheumatoid arthritis: a cross-sectional study

BackgroundDiet plays an important role in regulating inflammation, which is a hallmark of rheumatoid arthritis (RA). Our aim was to investigate the association between the Dietary Inflammatory Index (DII) scores and RA activity.MethodsThis cross-sectional study was conducted on 184 patients with RA in rheumatology clinic in Kermanshah city, Iran, in 2020. RA was diagnosed according to the criteria of the 2010 American College of Rheumatology/ European League against Rheumatism. The overall inflammatory potential of the diet was extracted from a validated 168-item food frequency questioner (FFQ) using the DII. RA disease activity was assessed using Disease Activity Score 28 (DAS-28) scores. Logistic regression and one-way ANOVA/ ANCOVA were conducted.ResultsIndividuals in the highest DII quartile had the significantly higher odds of positive C-reactive protein than those in the lowest quartile of the DII scores (OR 4.5, 95% CI 1.16 – 17.41, P = 0.029). A statistically significant downward linear trend in fat-free mass and weight were observed with increasing the DII quartiles (P = 0.003, P = 0.019, respectively). Patients in the highest DII quartile had higher DAS-28 scores than those in the first quartile (Mean difference: 1.16, 95% CI 0.51 – 1.81, P < 0.001) and second quartile of the DII scores (Mean difference: 1.0, 95% CI 0.34 – 1.65, P < 0.001).ConclusionOur results indicated that reducing inflammation through diet might be one of the therapeutic strategies to control and reduce the disease activity in RA patients.

Articular 18Fluorodeoxyglucose Uptake Is Associated With Clinically Assessed Swollen Joint Count in Patients With Rheumatoid Arthritis.

Examination and conventional radiography of joints are unable to precisely evaluate and measure disease activity in rheumatoid arthritis (RA). We quantified joint inflammation using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in people with RA to determine if PET-derived uptake variables were correlated with RA disease activity measures. We cross-sectionally studied 34 patients with RA in a substudy of the Rheumatoid Arthritis Study of the Myocardium (RHYTHM). All patients underwent 18F-FDG-PET scanning with CT for attenuation correction and anatomic co-registration. Linear regression was used to model the associations of disease activity scores with articular FDG uptake, calculated as standardized uptake values (SUVs). Weighted joint volume SUVs (wjSUV) representing 25%, 50%, 75%, and maximum (100%) uptake (wj25SUV, wj50SUV, wj75SUV, and wjMaxSUV, respectively) were calculated as global variables of the total volume of joint inflammation in each patient. Calculated wj25SUV (Spearman ρ = 0.39, P = 0.04), wj50SUV (ρ = 0.39, P = 0.04), and wj75SUV (ρ = 0.37, P = 0.045) measures were significantly correlated with the number of swollen joints. Similar significant correlations were found for the Simplified Disease Activity Index but not Clinical Disease Activity or Disease Activity Score in 28 joints. No associations were found between articular FDG uptake and nonarticular RA-related variables (ie, disease duration, seropositivity, or RA treatments). Articular FDG uptake in patients with RA was significantly correlated with the number of swollen joints but not with biochemical measures of inflammation.

Predictors of flare in rheumatoid arthritis patients with persistent clinical remission/low disease activity: Data from the TARAC cohort.

To identify predictors of rheumatoid arthritis (RA) disease activity flare in RA patients who achieved low disease activity (LDA) or persistent remission from the observational Thai Army Rheumatoid Arthritis Cohort study.RA patients with persistent clinical remission, defined by disease activity score 28 (DAS28) < 2.6 and LDA defined by DAS28 ≤ 3.2 for 3 consecutive months, were recruited and followed-up for at least 2 years. The flare was defined by an escalation of DAS28 ≥ 1.2 plus their physicians’ decision to enhance RA treatment. Differences between sustained remission/LDA and flare groups were analyzed, by Chi-square test and unpaired Student t test. Multivariate Cox proportional hazard regression analysis was conducted to determine flare predictors.From 199 RA patients, female were 82.9%. Anticitrullinated peptide antibodies (ACPA) or Rheumatoid factor (RF) were found in 69.8% of patients. Flares occurred in 69 patients (34.9%). Multivariate analysis found that the timescale from symptoms emergence to DMARD commencement, the timescale from DMARD commencement to when RA patients showed remission/LDA, the occurrence of RF or ACPA, LDA (in contrast to remission) and the increased DAS28 score when remission/LDA was achieved and tapering DMARDs promptly when persistent remission/LDA was achieved were predictors of RA flares with hazard ratios of (95% confidence interval [CI]) of 1.017 (1.003–1.030), 1.037 (1.015–1.059), 1.949 (1.035–3.676), 1.926 (0.811–4.566), 2.589 (1.355–4.947), and 2.497 (1.458–4.276), respectively.These data demonstrated that early and aggressive DMARDs treatment approach could maintain remission espcially in seropositive patients. Tapering should be applied minimally 6 months after reaching remission.

Ultrasound joint examination by an automated system versus by a rheumatologist: from a patient perspective

BackgroundThe Arthritis Ultrasound Robot (ARTHUR) is an automated system for ultrasound scanning of the joints of both hands and wrists, with subsequent disease activity scoring using artificial intelligence. The objective was to describe the patient’s perspective of being examined by ARTHUR, compared to an ultrasound examination by a rheumatologist. Further, to register any safety issues with the use of ARTHUR.MethodsTwenty-five patients with rheumatoid arthritis (RA) had both hands and wrists examined by ultrasound, first by a rheumatologist and subsequently by ARTHUR. Patient-reported outcomes (PROs) were obtained after the examination by the rheumatologist and by ARTHUR. PROs regarding pain, discomfort and overall experience were collected, including willingness to be examined again by ARTHUR as part of future clinical follow-up. All ARTHUR examinations were observed for safety issues.ResultsThere was no difference in pain or discomfort between the examination by a rheumatologist and by ARTHUR (p = 0.29 and p = 0.20, respectively). The overall experience of ARTHUR was described as very good or good by 92% (n = 23), with no difference compared to the examination by the rheumatologist (p = 0.50). All (n = 25) patients were willing to be examined by ARTHUR again, and 92% (n = 23) would accept ARTHUR as a regular part of their RA clinical follow up. No safety issues were registered.ConclusionsJoint ultrasound examination by ARTHUR was safe and well-received, with no difference in PRO components compared to ultrasound examination by a rheumatologist. Fully automated systems for RA disease activity assessment could be important in future strategies for managing RA patients.Trial registration: The study was evaluated by the regional ethics committee (ID: S-20200145), which ruled it was not a clinical trial necessary for their approval. It was a quality assessment project, as there was no intervention to the patient. The study was hereafter submitted and registered to Odense University Hospital, Region of Southern Denmark as a quality assessment project and approved (ID: 20/55294).

Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis

SummaryWe aimed to evaluate the association between adipose tissue (AT) dysfunction, autoimmunity, and disease activity in rheumatoid arthritis (RA). A cross-sectional study including 150 RA patients and 50 healthy donors and longitudinal study with 122 RA patients treated with anti-tumor necrosis factor (TNF)-α, anti-interleukin 6 receptor (IL6R) or anti-CD20 therapies for 6 months were carried out. In vitro experiments with human AT and adipocyte and macrophage cell lines were performed. A collagen-induced arthritis mouse model was developed. The insulin resistance and the altered adipocytokine profile were associated with disease activity, the presence of anti-citrullinated proteins anti-bodies (ACPAs), and worse response to therapy in RA. AT in the context of arthritis is characterized by an inflammatory state alongside the infiltration of macrophages and B/plasmatic cells, where ACPAs can have a direct impact, inducing inflammation and insulin resistance in macrophages and promoting a defective adipocyte differentiation, partially restored by biologicals.

Increased Circulating Pentraxin 3 Levels in Patients with Rheumatoid Arthritis: A Meta-analysis.

Pentraxin 3 (PTX3), a soluble pattern recognition molecule, not only acts as a promising indicator reflecting the disease activity of rheumatoid arthritis (RA) patients but exerts essential pathogenic roles in the progression of RA and serves as a potential therapeutic target for RA patients. Our study intends to systematically evaluate the circulating PTX3 levels and their potential influencing factors in RA patients. Articles regarding the circulating PTX3 levels of RA patients were identified in Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases. Standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were calculated and further illustrated by the forest plot. Egger's regression test and sensitivity analysis were conducted to assess the publication bias and stability of the results, respectively. Twenty articles with 21 individual studies were recruited in our meta-analysis. The overall results revealed that compared to healthy controls, RA patients had significantly higher circulating PTX3 levels (pooled SMD = 0.97, 95% CI: 0.48 to 1.45). Subgroup analyses further demonstrated that compared to healthy controls, RA patients of age ≤ 50 years, 2.6 < disease activity score in 28 joints (DAS28) ≤ 3.2, 3.2 < DAS28 ≤ 5.1, DAS28 > 5.1, C-reactive protein (CRP) levels > 10 mg/L, erythrocyte sedimentation rate (ESR) > 20 mm/h, and disease duration > 5 years had significantly higher circulating PTX3 levels, respectively; whereas RA patients of age > 50 years, DAS28 ≤ 2.6, CRP levels ≤ 10 mg/L, ESR ≤ 20 mm/h and disease duration ≤ 5 years had no significantly altered circulating PTX3 levels, respectively. Additionally, no matter whether the patients were of Caucasian ethnicity or not, circulating PTX3 levels were significantly increased in RA patients. Compared to healthy controls, circulating PTX3 levels are significantly increased in RA patients, which are influenced by age, disease activity, CRP levels, ESR, and disease duration.

Red cell distribution width and mean platelet volume in rheumatoid arthritis patients: Its association with disease activity

IntroductionHemogram parameters have been recently proposed as markers of inflammation in various studies from different parts of the world. Two of these hemogram parameters are red cell distribution width (RDW) and mean platelet volume (MPV). AimTo evaluate the relation between RDW and MPV with disease activity of rheumatoid arthritis. To assess whether RDW and MPV can be used to follow disease activity in RA patients. MethodsThis is an observational cross-sectional study that was carried out on 60 rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were subjected to full history taking, clinical examination, and laboratory investigations; differential complete blood picture (CBC), acute phase reactants (CRP and ESR), rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (anti-CCP) antibodies. Disease activity was measured by disease activity score 28 (DAS28). ResultsThe cut-off levels of RDW and MPV were 14.85 and 11.25. Patients with RDW>14.85 had higher Disease Activity Score 28 (DAS28; p=0.0003), ESR (p=0.0001) and CRP (p=0.0001). RDW was positively correlated with disease activity markers (ESR, CRP and DAS28) in rheumatoid arthritis patients. But, DAS28 was not different between patients with MPV>11.25 and <11.25. ConclusionRDW was strongly correlated with disease activity. Also, RDW was better than ESR and CRP in detecting RA disease activity. According to these findings we suggest that RDW can be used in clinics to follow disease activity. In addition, RDW is widely available; as it's usually included in routine complete blood picture and there will be no need for further cost.

Immature platelet fraction in rheumatoid arthritis with interstitial lung disease

BackgroundPlatelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD. MethodsThe study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany. ResultsiPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity. ConclusionsOur results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.

Immature Platelet Fraction in Rheumatoid Arthritis with Interstitial Lung Disease.

Platelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD. The study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany. iPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity. Our results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.

Inflammatory Arthritis Facilitators and Barriers (IFAB) for physical activity questionnaire: cross-cultural adaptation into Turkish and evaluation of its psychometric properties

Purpose We aimed to conduct the translation and cross-cultural adaptation of the Inflammatory arthritis Facilitators and Barriers (IFAB) questionnaire into Turkish language for patients with axial spondyloarthritis (axSpA) and analyze the psychometric properties of the IFAB-Turkish version (IFAB-Tr). Methods Data from ninety-three patients with axSpA were analyzed who completed the IFAB-Tr, Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS) and Bath Ankylosing Spondylitis Functional Index (BASFI). Internal consistency, test-retest reliability, convergent validity, floor and ceiling effect, measurement error were examined. Exploratory factor analysis (EFA) and confirmatory factor analysis were conducted. Results Small modification was needed in the translation and cultural adaptation process. Internal consistency of the IFAB-Tr total score was 0.71 and test-retest reliability was excellent for IFAB-Tr (ICC = 0.90). A moderate negative correlation was found between IFAB-Tr total score and HAQ, HADS, BASFI scores. No floor and ceiling effect was detected. Minimal detectable change was 10.34 points. EFA revealed two factors which accounted for 55% of the variance. Conclusions The IFAB was successfully translated into the Turkish language and seems suitable for evaluating barriers and facilitators for physical activity in rheumatic diseases and could be used in clinical settings before designing a physical activity intervention. IMPLICATIONS FOR REHABILITATION The Turkish version of the Inflammatory arthritis FAcilitators and Barriers (IFAB) is a valid and reliable tool to assess barriers and facilitators to physical activity for patients with axial spondyloarthritis. More work is needed to assess all psychometric properties of the IFAB questionnaire in other inflammatory rheumatic disorders. The Inflammatory arthritis FAcilitators and Barriers questionnaire in Turkish is an easy and quick way to determine potential barriers to physical activity in clinical and research settings.

MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in rheumatoid arthritis

ObjectiveMALT1 regulates immunity and inflammation in multiple ways, while its role in rheumatoid arthritis (RA) is obscure. This study aimed to investigate the relationship of MALT1 with disease features, treatment outcome, as well as its effect on Th1/2/17 cell differentiation and underlying molecule mechanism in RA.MethodsTotally 147 RA patients were enrolled. Then their blood Th1, Th2, and Th17 cells were detected by flow cytometry. Besides, PBMC MALT1 expression was detected before treatment (baseline), at week (W) 6, W12, and W24. PBMC MALT1 in 30 osteoarthritis patients and 30 health controls were also detected. Then, blood CD4+ T cells were isolated from RA patients, followed by MALT1 overexpression or knockdown lentivirus transfection and Th1/2/17 polarization assay. In addition, IMD 0354 (NF-κB antagonist) and SP600125 (JNK antagonist) were also added to treat CD4+ T cells.ResultsMALT1 was increased in RA patients compared to osteoarthritis patients and healthy controls. Meanwhile, MALT1 positively related to CRP, ESR, DAS28 score, Th17 cells, negatively linked with Th2 cells, but did not link with other features or Th1 cells in RA patients. Notably, MALT1 decreased longitudinally during treatment, whose decrement correlated with RA treatment outcome (treatment response, low disease activity, or disease remission). In addition, MALT1 overexpression promoted Th17 differentiation, inhibited Th2 differentiation, less affected Th1 differentiation, activated NF-κB and JNK pathways in RA CD4+ T cells; while MALT1 knockdown exhibited the opposite effect. Besides, IMD 0354 and SP600125 addition attenuated MALT1’s effect on Th2 and Th17 differentiation.ConclusionMALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in RA.

Correlation of CRP genotypes with serum CRP levels and the risk of rheumatoid arthritis in Chinese Han population.

C-reactive protein (CRP) is an important index for evaluating the disease activity of rheumatoid arthritis (RA). CRP may play a direct role in bone destruction in RA. Studies have demonstrated that serum CRP levels had a close correlation with tissue inflammation scores in patients with RA. In addition, genetic factors play a crucial role in the development of RA. In this study, we aimed to investigate the relationship between the CRP gene variants (rs1205 polymorphism) and the risk of RA in Chinese Han population. 502 RA patients and 581 controls were included in this study. The associations between CRP gene variants and CRP levels and RA risk were investigated. We found that TT/ TT + CT genotype was significantly related with an increased risk of RA (TT vs CC: OR, 1.56, 95%CI, 1.01-2.40, P = 0.045; TT + CT vs CC: OR, 1.30, 95%CI, 1.02-1.65, P = 0.032). In addition, T allele was shown to associate with an elevated risk of RA. After subgroup analysis, we found that rs1205 polymorphism was significantly related with an enhanced risk of RA among females, individuals lower than 60years, and subjects with a BMI > 25kg/m2. Furthermore, data showed that the CRP gene rs1205 polymorphism correlated with CRP and ESR levels. Furthermore, the TT genotype was significantly associated with a reduction of CRP levels compared with CT or CC genotype. To sum up, this study reveals that rs1205 polymorphism of the CRP gene is related with an increased risk of RA and CRP levels in Chinese Han population. Key Points • The CRP gene rs1205 polymorphism is related with a higher risk of RA. • The CRP gene rs1205 polymorphism correlates with CRP and ESR levels. • The TT genotype of rs1205 polymorphism is linked with a reduction of CRP levels.

Safety and Biological Activity of Rozibafusp alfa, a Bispecific Inhibitor of Inducible Costimulator Ligand and B Cell Activating Factor, in Patients With Rheumatoid Arthritis: Results of a Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study.

ObjectiveTo assess the safety and biological activity of rozibafusp alfa, a first‐in‐class bispecific antibody–peptide conjugate targeting inducible costimulator ligand (ICOSL) and B cell activating factor (BAFF), in patients with rheumatoid arthritis (RA).MethodsThis phase 1b, double‐blind, placebo‐controlled, multiple ascending dose study included 34 patients (18–75 years; 82.4% female) with active RA (Disease Activity Score of 28 joints–C‐reactive protein [DAS28‐CRP] >2.6, on stable methotrexate) randomized 3:1 to receive rozibafusp alfa (n = 26, in four ascending dose cohorts of 70, 140, 210, and 420 mg) or a placebo (n = 8) subcutaneously once every 2 weeks for 10 weeks (six total doses), with 24 weeks of follow‐up. The primary end point was the incidence of treatment‐emergent adverse events (TEAEs). Additional assessments included serum pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and RA disease activity measures (DAS28‐CRP, Patient Global Assessment of Disease, and Physician Global Assessment of Disease).ResultsTEAEs occurred in 96.2% and 87.5% of patients receiving rozibafusp alfa and the placebo, respectively; most were mild or moderate in severity. Two (7.7%) patients treated with rozibafusp alfa reported serious TEAEs; none were considered treatment related. Multiple doses of rozibafusp alfa showed nonlinear PK (mean t 1/2 = 4.6–9.5 days) and dose‐related, reversible PD (>90% ICOSL receptor occupancy in 210‐ and 420‐mg cohorts; reduction in naïve B cells and increase in memory B cells in all cohorts). Five (20%) patients developed anti–rozibafusp alfa antibodies, with no apparent impact on safety. RA disease activity showed greater numerical improvement from baseline with rozibafusp alfa versus the placebo in the 210‐ and 420‐mg cohorts.ConclusionMultiple ascending doses of rozibafusp alfa were well tolerated, with PK and PD reflecting dual ICOSL and BAFF blockade. Findings support further clinical evaluation of rozibafusp alfa in autoimmune disease.

NR4A1-3 nuclear receptor activity and immune cell dysregulation in rheumatic diseases.

The development and progression of immune-mediated rheumatic disease (IMRD) involves dysfunction of innate and adaptive immune cell populations leading to altered responses including inflammasome activation, dysregulated cytokine networks, increased immune cell numbers and multifaceted cell-cell communication. Several rheumatic diseases are further characterized by the presence of autoantibodies, immune complex mediated complement activation and the deficit of peripheral immune tolerance due to reduced regulatory T-lymphocyte cell function. Ultimately, in rheumatic disease the loss in cellular and tissue homeostasis culminates in the advancement of chronic inflammation. The three members of the NR4A subfamily of nuclear receptors are immediate early genes, and act as potent transcriptional responders to changes in the cellular and tissue microenvironment. Subfamily members are rapidly expressed in diseases characterized by inflammation and function to control the differentiation and activity of innate and adaptive immune cells in a cell-type and cell-context specific manner. Rheumatic disease including rheumatoid-, psoriatic-, osteo-arthritis and systemic sclerosis display altered NR4A1-3 activity in controlling immune cell migration and function, production of paracrine signaling molecules, synovial tissue hyperplasia, and regulating cartilage turn-over in vivo. Additionally, NR4A1-3 activities mediate cytokine, prostanoid and growth factor signaling to control angiogenesis, modulate the regulatory functions of mesenchymal stromal cells, alter the activation status of dendritic cells, influence the generation of peripheral myeloid and T-lymphocyte lineages and promote the maintenance of functional regulatory T-cells. Further reports uncover the potential of moderating NR4A 1-3 receptors as therapeutic targets in altering immune tolerance, pathological angiogenesis and controlling inflammation in several models of disease.

Treatment resistance of rheumatoid arthritis relates to infection of periodontal pathogenic bacteria: a case–control cross-sectional study

Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case–control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (≥ 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA.

Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

Background: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. Methods: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7–9, n-3 and n-6 FAs (patterns ω7–9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. Results: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). Conclusions: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

The Economic Benefit of Remission for Patients with Rheumatoid Arthritis.

IntroductionIn patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy.MethodsThis retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010–3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted.ResultsOf 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher.ConclusionsCost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00473-6.

Regulatory T Cells from Patients with Rheumatoid Arthritis Are Characterized by Reduced Expression of Ikaros Zinc Finger Transcription Factors.

Regulatory T (Treg) cells play an important role in immune tolerance and contribute to the prevention of autoimmune diseases, including rheumatoid arthritis (RA). The differentiation, function and stability of Treg cells is controlled by members of the Ikaros zinc finger transcription factor family. In this study, we aimed to reveal how the expression of Ikaros transcription factors is affected by disease activity in RA. Therefore, we analyzed the ex vivo expression of Ikaros, Helios, Aiolos and Eos in Treg cells, Th17 cells and Th1 cells from RA patients by flow cytometry. We found significantly reduced expression of Helios, Aiolos and Eos in Treg cells from RA patients as compared to healthy controls. Moreover, Helios and Aiolos levels correlated with disease activity, as assessed by DAS28-CRP. In addition, Ikaros, Helios and Aiolos were significantly downregulated in Th1 cells from RA patients, while no difference between healthy individuals and RA was observed in Th17 cells. In summary, Helios and Aiolos expression in Treg cells correlates with disease activity and the expression levels of Ikaros transcription factors are diminished in Treg cells from RA patients. This observation could explain the reduced stability of Treg cells in RA.

Comparison of Hand Features in Systemic Sclerosis and Rheumatoid Arthritis Patients by Diagnostic Ultrasound and its Correlation to Disease Activity, Clinical and Radiological Findings

Introduction and Aim: Imaging evaluation of the rheumatoid arthritis and systemic sclerosis represents a significant part in disease evaluation and follow up. However, it had many limitations and new tools are introduced continuously. The current work aimed to compare ultrasound characteristics of the hand involvement in systemic sclerosis (SSc) and rheumatoid arthritis (RA).&#x0D; Patients and methods: The study included 30 SSc and 40 RA patients. All were evaluated by the full history taking, detailed clinical examination, disease activity scores and the health assessment questionnaires were completed. All necessary laboratory investigations were performed. Finally, radiological examination (plain X-rays and ultrasound for joints of hands and wrist) was performed.&#x0D; Results: Patient age ranged from 22 to 58 years, and RA patients were significantly older, with female sex predominance. SSc was of diffuse (30%) and (70%) were of limited type. The disease activity of RA ranged from 2 to 9, while disease activity of SSc ranged between 1.3 to 3.5. In the SSc group, 56.7% had active disease compared to 40% in RA groups. Patients in the SSc group had a degree of disability, while 82.5% of patients in the RA group had mild- to- moderate disability. Ultrasound examination revealed that, synovitis was significantly increased in RA when compared to the SSc group (55.0% vs 23.3%). The sclerosing pattern of tenosynovitis was significantly increased in SSc than the RA group (92.3% vs 0.0% respectively). Results of ultrasound completely coincides with results of MRI. Finally, there was statistically significant, moderate, proportional correlation between ultrasound and each of erythrocyte sedimentation rate (ESR), and disease activity scores.&#x0D; Conclusion: Ultrasound hand examination in scleroderma and RA is more accurate than separate clinical or X-ray examinations. However, it could not completely substitute clinical examination. But it is a suitable add on especially in detection of early disease activity.

Clinical Significance of Prolactin Level in the Assessment of Rheumatoid Arthritis Disease Activity and Severity

Clinical Significance of Prolactin Level in the Assessment of Rheumatoid Arthritis Disease Activity and Severity