Rheumatoid Arthritis Disease Activity Research Articles

Using the derived 28-joint disease activity score patient-reported components (DAS28-P) index as a discriminatory measure of response to disease-modifying anti-rheumatic drug therapy in early rheumatoid arthritis

BackgroundThe 28-joint disease activity score (DAS28) is a widely used measure to assess disease activity in rheumatoid arthritis (RA). The DAS28-P index, a derived proportion of the patient-reported components (joint tenderness and patient global assessment) within the DAS28, has been utilized as a discriminatory measure of non-inflammatory pain mechanisms in RA. This study aimed to evaluate the use of the DAS28-P index as a predictor of treatment response in early RA.MethodsPatients with early RA enrolled in a supplemental fish oil clinical trial received a combination of disease-modifying anti-rheumatic drugs (DMARDs) according to a ‘treat-to-target’ protocol. First, consecutive measures of the DAS28-P index, derived from the DAS28-erythrocyte sedimentation rate (DAS28-ESR), at each visit over a 1-year period were estimated for each patient. Then, distinct subgroups of treatment responders based on the trajectories of the DAS28-P indices were identified using bivariate k-means cluster analysis. Data on baseline predictors as well as longitudinal outcomes of disease impact and DMARD use over a 1-year period and radiographic progression over a 3-year period were collected and analyzed using a random intercept, population-averaged generalized estimating equation model.Results121 patients were included (74% female; mean age of 57; median of 16 weeks of active disease) and a 3-cluster model was identified—the ‘Responders’ group (n = 58; 48%), the ‘Partial Responders’ group (n = 32; 26%), and the ‘Non-Responders’ group (n = 31; 26%). The ‘Partial Responders’ group had consistently higher proportions of the DAS28-P index throughout the study period and had minimal radiographic progression over time, with the lowest joint erosion score of 0.9 [95% confidence interval (CI) 0.2, 1.6], observed at the 3-year follow-up. At 52 weeks, the methotrexate dose was higher for both ‘Partial Responders’ and ‘Non-Responders’ groups (18.5 mg [95% CI 15.5, 21.5] and 18.6 mg [95% CI 15.3, 21.8] respectively), when compared with the ‘Responders’ group (12.8 mg [95% CI 14.7, 20.9]).ConclusionsPersistently high DAS28-P index scores are useful to distinguish poor patient global assessment and excessive treatment escalation in early RA, suggestive of underlying non-inflammatory pain contributing to higher disease activity score. Early identification of patients with discordant subjective and objective components of composite disease activity measures may allow better tailoring of treatment in RA.

CD169+ Monocyte and Regulatory T Cell Subsets Are Associated with Disease Activity in Rheumatoid Arthritis.

Disease activity in rheumatoid arthritis (RA) is influenced by activation of circulating and synovial immune cells. Regulatory T cells (Tregs) and monocytes are key cells that drive inflammation in RA. This study investigated if a relationship exists between disease activity in RA and circulating Treg and monocyte numbers and phenotypes. A potential sialic acid (Sia) mediated link between Tregs and monocytes was also probed in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patient (n = 62) and healthy control (n = 21) blood using density gradient separation. Flow cytometry was used to count and phenotype Treg and monocyte subsets, and to sort healthy control Tregs for Sia cell culture experiments. The effects of Sia on activated Treg FoxP3 and NFκB expression was assessed by flow cytometry and concentrations of secreted TNFα, IL-10 and IFNγ determined by ELISA. High disease activity RA patients who were unresponsive to disease modifying anti-rheumatic drugs (n = 31), have significantly lower relative numbers (percentages) of CD4+CD25+CD127- Tregs (p < 0.01) and memory CD45RA-FoxP3+ Tregs (p < 0.01), compared to low disease activity responders (n = 24). Relative numbers of non-classical CD169+ monocytes are associated with disease activity in RA (p = 0.012). Sia reduced Treg expression of FoxP3, NFκB and cytokines in vitro. A strong association has been identified between non-classical CD169+ monocytes and post-treatment disease activity in RA. This study also indicates that Sia can reduce Treg activation and cytokine release. We postulate that such a reduction could be mediated by interaction with sialyted proteins captured by CD169+ monocytes.

Evaluation of thiol/disulfide homeostasis in rheumatoid arthritis and disease activity

BackgroundIt has been suggested that the deterioration in the antioxidant defense system due to thiols may cause the pro-oxidant/antioxidant imbalance seen in rheumatoid arthritis (RA). This study was conducted to evaluate thiol/disulfide (−SH/−SS) homeostasis in patients with RA compared to healthy controls, and to validate the limited number of studies examining the relationship between Disease Activity Score-28 (DAS28) and thiol parameters. MethodA total of 100 individuals (mean age: 46.3 ± 12.03) consisting of 86 females and 14 males were included in the RA group, and a total of 100 individuals (mean age: 43.3 ± 10.96 years) consisting of 78 females and 22 males were included in the control group. DAS28 was used to assess RA disease activity. −SH/−SS homeostasis parameters were measured using the automated spectrophotometric method described by Erel and Neselioğlu. ResultsWhile native thiol (−SH) (p:0.001), total thiol (−SH + −SS) (p < 0.0001) levels and −SH\\(−SS + −SH) ratio (p: 0.018) were lower in the RA group compared to the healthy controls, disulfide (−SS) level (p: 0.005)), −SS\\−SH (p: 0.001) and −SS\\(−SS + -SH) (p: 0.002) ratios were found to be higher. In the control group and the group in remission (defined by DAS28 < 2.6), the median values of –SH (p:0.002) and −SS + −SH (p:0.0008) were found to be significantly higher, and the median value of –SS (p: 0.001) was found to be lower compared to the other DAS28 groups. While a negative correlation was found between DAS28 and –SH (r: −0.243, p: 0.007), a positive correlation was found between DAS28 and −SS (r: 0.316, p: 0.0003), −SS\\−SH (r:0.229, p: 0.002) and −SS\\(−SS + −SH) (r: 0.285, p: 0.0009). ConclusionsThe plasma thiol antioxidant pool was decreased in RA compared to healthy controls and those with active disease compared to those in remission.

Abstract 11968: Association Between Reduction in Inflammation and Change in Cardiovascular Risk: Results From the Liira Study

Background: Coronary microvascular disease (CMD) is associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Studies suggest that higher RA disease activity is associated with a higher degree of CMD, as measured by coronary flow reserve (CFR). However, it is not known whether reducing inflammation results in improvement in CMD or other CV correlates. The objective of this study was to determine the association between reducing inflammation with changes in CV risk. Methods: The Lipids, Inflammation and CV risk in RA (LiiRA) study recruited RA patients age ≥18 yrs with active RA about to initiate a TNFi as part of clinical care. All subjects underwent a stress myocardial perfusion PET scan to quantify CFR at baseline and after 24 weeks. A lower CFR in the absence of obstructive CAD is indicative of CMD, CFR&lt; 2.5 defined CMD. Inflammatory markers and hs-cTnT were performed at baseline and 24 weeks. Primary and secondary outcomes was change in CFR and hs-cTnT, respectively, and tested by Spearman correlations. Results: A total of 66 subjects completed the study, 80% female, mean RA duration 7.7 yrs. Baseline estimated ASCVD risk was 5.6%, yet 47% had evidence of CMD. We observed a significant reduction in all inflammatory markers between baseline and follow-up, along with improvements in RA disease activity; however, no change in the mean CFR or hs-cTnT was observed. A reduction in hsCRP and IL-1beta was associated with a reduction in hs-cTnT. A non-significant trend for correlation of reduced IL-1beta with higher CFR was observed among subjects with CMD at baseline (Figure). Conclusion: There was a high prevalence of CMD at baseline, but CFR did not significantly improve. Reducing inflammation was correlated with improvements in measures of CV risk, mainly in the subset of patients with detectable hs-cTnT, particularly via the IL-1beta pathway. These data suggest that hs-cTnT may be a useful marker when considering targeting inflammation to reduce CV risk in RA.

To eat or not to eat-an exploratory randomized controlled trial on fasting and plant-based diet in rheumatoid arthritis (NutriFast-Study).

Fasting is beneficial in many diseases, including rheumatoid arthritis (RA), with lasting effects for up to 1 year. However, existing data dates back several decades before the introduction of modern therapeutic modalities. This exploratory RCT compares the effects of a 7-day fast followed by a plant-based diet (PBD) to the effects of the dietary recommendations of the German society for nutrition (Deutsche Gesellschaft für Ernährung, DGE) on RA disease activity, cardiovascular (CV) risk factors, and well-being. In this RCT we randomly assigned 53 RA patients to either a 7-day fast followed by an 11-week PBD or a 12-week standard DGE diet. The primary endpoint was the group change from baseline to 12 weeks on the Health Assessment Questionnaire Disability Index (HAQ-DI). Further outcomes included other disease activity scores, body composition, and quality of life. Of 53 RA patients enrolled, 50 participants (25 per group) completed the trial and were included into the per-protocol analysis. The primary endpoint was not statistically significant. However, HAQ-DI improved rapidly in the fasting group by day 7 and remained stable over 12 weeks (Δ-0.29, p = 0.001), while the DGE group improved later at 6 and 12 weeks (Δ-0.23, p = 0.032). DAS28 ameliorated in both groups by week 12 (Δ-0.97, p < 0.001 and Δ-1.14, p < 0.001; respectively), with 9 patients in the fasting but only 3 in the DGE group achieving ACR50 or higher. CV risk factors including weight improved stronger in the fasting group than in the DGE group (Δ-3.9 kg, p < 0.001 and Δ-0.7 kg, p = 0.146). Compared with a guideline-based anti-inflammatory diet, fasting followed by a plant-based diet showed no benefit in terms of function and disability after 12 weeks. Both dietary approaches had a positive effect on RA disease activity and cardiovascular risk factors in patients with RA. https://clinicaltrials.gov/ct2/show/NCT03856190, identifier: NCT03856190.

PSTPIP2 regulates synovial macrophages polarization and dynamics via ERβ in the joint microenvironment

BackgroundThe cytoskeletal protein, PSTPIP2, is associated with inflammation and is predominantly expressed in macrophages. Previous data have shown that PSTPIP2 inhibits articular bone damage in arthritic rats. The aim of this study is to explore the molecular mechanism of PSTPIP2’s resistance to bone erosion.MethodsIn the current study, peripheral blood and surgically excised synovial tissue from RA patients, DBA/1 mice, Pstpip2CreR26-ZsGreen reporter mice, and Esr2fl/fl/Adgre-Cre tool mice were used for in vivo studies. Adeno-associated viral vector was used to overexpress PSPTIP2 protein in vivo.ResultsWe found that The level of PSTPIP2 in synovial macrophages is negatively correlated with RA disease activity, which is mediated by synovial macrophages polarization. PSTPIP2hi synovial macrophages form a tight immunological barrier in the lining layer. Notably, the ability of PSTPIP2 to regulate synovial macrophages polarization is dependent on ERβ. Additionally, PSTPIP2 regulates the dynamics of synovial macrophages via ERβ.ConclusionsTogether, this study reveals that PSTPIP2 regulates synovial macrophages polarization and dynamics via ERβ to form an immunological barrier (F4/80+PSTPIP2hi cell-enriched zone) for the joints. Thus, local modulation of PSTPIP2 expression in the joint microenvironment may be a potential strategy for controlling bone erosion in rheumatoid arthritis.Graphical PSTPIP2 regulates synovial macrophages polarization and dynamics via ERβ to form F4/80+PSTPIP2hi cellular barrier in joint microenvironment.

The Correlation of IL-6 Levels With the Degree of Rheumatoid Arthritis Disease Activity at Dr. Mohammad Hoesin Palembang

Rheumatoid arthritis (RA) is an autoimmune disease that requires careful management and regular evaluation of the degree of disease activity. AR is known for its pathophysiology and is strongly influenced by the increase of proinflammatory cytokines, especially IL-6. This study was conducted to determine the correlation of IL-6 levels with the degree of disease activity in AR patients at Dr. Mohammad Hoesin Palembang. A cross-sectional study was conducted on RA patients at the Rheumatology Polyclinic, Department of Internal Medicine, Dr. Moh Hoesin Palembang, who met the inclusion criteria consecutively in October 2021. The degree of RA disease activity was assessed using the Disease Activity Score (DAS 28). Statistical analysis was performed using SPSS version 24.0. A total of 34 subjects participated in the study, with most being women and a median age of 49.5 years. The majority of subjects had a moderate-high degree of RA activity. There is no significant correlation between IL-6 levels with DAS 28 CRP (r=0.256, p=0.072) and DAS 28 LED (r= 0.056, p=0.376). There was no significant correlation between serum IL-6 levels and disease activity in Rheumatoid Arthritis patients at Dr. Mohammad Hoesin Palembang.

Red Cell Distribution Width and Absolute Lymphocyte Count Associate With Biomarkers of Inflammation and Subsequent Mortality in Rheumatoid Arthritis.

Morbidity and mortality in rheumatoid arthritis (RA) is partly mitigated by maintaining immune and hematologic homeostasis. Identification of those at risk is challenging. Red cell distribution width (RDW) and absolute lymphocyte count (ALC) associate with cardiovascular disease (CVD) and mortality in the general population, and with disease activity in RA. How these variables relate to inflammation and mortality in RA was investigated. In a retrospective single Veterans Affairs (VA) Rheumatology Clinic cohort of 327 patients with RA treated with methotrexate (MTX)+/- a tumor necrosis factor (TNF) inhibitor (TNFi), we evaluated RDW and ALC before and during therapy and in relation to subsequent mortality. Findings were validated in a national VA cohort (n = 13,914). In a subset of patients and controls, we evaluated inflammatory markers. In the local cohort, high RDW and low ALC prior to MTX treatment was associated with subsequent mortality over 10 years (both P < 0.001). The highest mortality was observed in those with both high RDW and low ALC. This remained after adjusting for age and comorbidities and was validated in the national RA cohort. In the immunology cohort, soluble and cellular inflammatory markers were higher in patients with RA than in controls. ALC correlated with age, plasma TNF receptor II, natural killer HLA-DR mean fluorescence intensity, and CD4CM/CD8CM HLA-DR/CD38%, whereas RDW associated with age and ALC. MTX initiation was followed by an increase in RDW and a decrease in ALC. TNFi therapy added to MTX resulted in an increase in ALC. RDW and ALC before disease-modifying antirheumatic drug therapy are associated with biomarkers of monocyte/macrophage inflammation and subsequent mortality. The mechanistic linkage between TNF signaling and lymphopenia found here warrants further investigation.

Gaming for Adherence to Medication using Ehealth in Rheumatoid arthritis (GAMER) study: a randomised controlled trial

ObjectiveTo examine the effect on adherence to disease modifying anti-rheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) of a serious game that targeted implicit attitudes toward medication.MethodsA multicentre randomised...

Locomotive syndrome in rheumatoid arthritis patients during the COVID-19 pandemic.

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories "GLFS-5" and "Social activities" were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in "Social activities" and that of "GLFS-5." Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00-1.22]) and CDAI (OR: 1.08 [95%CI: 1.00-1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

Development of a Natural Language Processing System for Extracting Rheumatoid Arthritis Outcomes From Clinical Notes Using the National Rheumatology Informatics System for Effectiveness Registry.

To accelerate the use of outcome measures in rheumatology, we developed and evaluated a natural language processing (NLP) pipeline for extracting these measures from free-text outpatient rheumatology notes within the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry. We included all patients in RISE (2015-2018). The NLP pipeline extracted scores corresponding to 8 measures of rheumatoid arthritis (RA) disease activity (DA) and functional status (FS) documented in outpatient rheumatology notes. Score extraction performance was evaluated by chart review, and we assessed agreement with scores documented in structured data. We conducted an external validation of our NLP pipeline using data from rheumatology notes from an academic medical center that is not included in the RISE registry. We processed over 34 million notes from 854,628 patients, 158 practices, and 24 electronic health record (EHR) systems from RISE. Manual chart review revealed a sensitivity, positive predictive value (PPV), and F1 score of 95%, 87%, and 91%, respectively. Substantial agreement was observed between scores extracted from RISE notes and scores derived from structured data (κ=0.43-0.68 among DA and 0.86-0.98 among FS measures). In the external validation, we found a sensitivity, PPV, and F1 score of 92%, 69%, and 79%, respectively. We developed an NLP pipeline to extract RA outcome measures from a national registry of notes from multiple EHR systems and found it to have good internal and external validity. This pipeline can facilitate measurement of clinical- and patient-reported outcomes for use in research and quality measurement.

Artificial Intelligence and Deep Learning for Rheumatologists.

Deep learning has emerged as the leading method in machine learning, spawning a rapidly growing field of academic research and commercial applications across medicine. Deep learning could have particular relevance to rheumatology if correctly utilized. The greatest benefits of deep learning methods are seen with unstructured data frequently found in rheumatology, such as images and text, where traditional machine learning methods have struggled to unlock the trove of information held within these data formats. The basis for this success comes from the ability of deep learning to learn the structure of the underlying data. It is no surprise that the first areas of medicine that have started to experience impact from deep learning heavily rely on interpreting visual data, such as triaging radiology workflows and computer-assisted colonoscopy. Applications in rheumatology are beginning to emerge, with recent successes in areas as diverse as detecting joint erosions on plain radiography, predicting future rheumatoid arthritis disease activity, and identifying halo sign on temporal artery ultrasound. Given the important role deep learning methods are likely to play in the future of rheumatology, it is imperative that rheumatologists understand the methods and assumptions that underlie the deep learning algorithms in widespread use today, their limitations and the landscape of deep learning research that will inform algorithm development, and clinical decision support tools of the future. The best applications of deep learning in rheumatology must be informed by the clinical experience of rheumatologists, so that algorithms can be developed to tackle the most relevant clinical problems.

Impact of specialty pharmacy collaboration with rheumatology clinics to improve the achievement of treat-to-target goals in patients with rheumatoid arthritis: a pilot study

In rheumatoid arthritis, the use of Routine Assessment of Patient Index Data 3 (RAPID3) assessments to meet treat-to-target goals is endorsed by the 2021 American College of Rheumatology guidelines. In November 2020, the Baylor Scott & White specialty pharmacy implemented a new service that included more frequent collection of RAPID3 scores and standardized provider communication for patients co-managed by a Baylor Scott & White rheumatology clinic. The objective was to evaluate the impact of this new service on rheumatoid arthritis disease activity. Before the new service started, patients followed a protocol of RAPID3 assessments that occurred every 6 months; once the service began, patients were followed using an algorithm in which patients with higher disease activity were contacted more frequently. Eighty-six percent of patients in the pre-intervention group (n = 7) compared with 100% of patients in the post-intervention group (n = 10) had high to moderate disease activity at baseline. Within a 6-month follow-up period in both groups, the percentage of high to moderate disease activity patients decreased by 30% in the post-intervention group and remained the same in the pre-intervention group. These results support the positive impact increased specialty pharmacy services may have on clinical outcomes; therefore, the continued expansion of these services should be considered.

Oral health-related quality of life in rheumatoid arthritis: a comparative analysis

BackgroundCompared to the healthy population, the psychological impact of rheumatoid arthritis(RA) on patients' lives could dramatically lower their oral health-related quality of life (OHRQoL). Our goal is to analyze OHRQoL in RA patients and look into the role of disease activity, dental health index, and Temporomandibular disorders score in maintaining their oral health.MethodsIn a cross-sectional comparative study, we compared a sample of 40 RA patients with 40 age- and gender-matched healthy controls in terms of oral health and OHRQoL. Temporomandibular disorders (TMD), number of decayed, filled, or missing teeth (DMFT), and Oral Health Impact Profile (OHIP) were among the oral health factors studied (OHIP-14). This study also looked at the link between the RA disease activity score (DAS28) and oral health factors.ResultsRA patients had a significantly higher mean (poorer OHRQol) than healthy controls in total oral function, total psychosocial impact, OHIP-14 sum score, OHIP-14 extent score, TMD score and the number of missed teeth (Mann–Whitney U test, P-value < 0.05). After adjustment for DMFT, only the oral function score of OHIP-14 had a significant correlation with disease activity (Mann–Whitney U test, P-value < 0.05). The TMD sum score significantly correlated with disease activity regardless of adjustment for DMFT (Spearman's Correlation test, P-value < 0.05 for both). The number of decayed teeth and missed teeth showed a positive correlation with increased disease activity (Coefficient = 0.239 and 0.245, P-value < 0.05 for both).ConclusionsPatients with RA are less satisfied with their oral health than healthy controls. In RA patients, the number of missing teeth and temporomandibular disorders was substantially greater, and the number of missing teeth and temporomandibular diseases increased significantly with increased disease activity. Although OHRQoL was inversely connected with RA activity, after correcting for decaying, missing, and filled teeth, only the oral function score of OHIP-14 exhibited a slight connection to DAS28.

Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review.

ObjectiveRheumatoid arthritis (RA) is an autoimmune disorder. Multiple studies have investigated the risk of thyroid dysfunction in patients with RA but have reached conflicting conclusions. This systematic review aimed to determine whether patients with RA are at higher risk of thyroid dysfunction.MethodsWe comprehensively reviewed online literature databases, including PubMed, Scopus, Embase, and the Cochrane Library, from their respective inception dates to March 25, 2022. Studies that provided data on at least one case of thyroid dysfunction in RA patients and their controls were included. Based on these data, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for thyroid dysfunction in RA and non-RA patients.ResultsTwenty-nine studies met the inclusion criteria, involving a total of 35,708 patients with RA. The meta-analysis showed that, compared with non-RA patients, RA patients had an increased risk of developing thyroid dysfunction, particularly hypothyroidism (OR 2.25, 95% CI 1.78–2.84). Subgroup analysis suggested that study type and sample source of control group were the source of heterogeneity.ConclusionsPatients with RA are at increased risk of developing thyroid dysfunction, especially hypothyroidism. Routine biochemical examination of thyroid function in RA patients should be strengthened. Larger prospective studies are needed to explore the causal relationship between RA and thyroid dysfunction, and to investigate the impact of thyroid dysfunction on RA disease activity, drug efficacy, and medication safety.Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022331142.

Examining the potential direct cardiovascular benefit of tumor-necrosis factor inhibitor in rheumatoid arthritis: Natural and controlled direct effect analyses.

Tumor necrosis factor inhibitors (TNFi) may have a direct benefit on cardiovascular (CV) disease beyond reducing rheumatoid arthritis (RA) disease activity measured by the Clinical Disease Activity Index (CDAI). We compared TNFi initiators and methotrexate (MTX) monotherapy initiators from the CorEvitas RA registry. Two approaches to the "direct effect" of TNFi beyond CDAI were used. In the natural direct effect (NDE) analysis, the potential CV benefit of TNFi was partitioned into NDE and the natural indirect effect (NIE) mediated by CDAI during the first 6 months. We also estimated the controlled direct effects (CDE), corresponding to the direct benefit of TNFi when CDAI trajectories were hypothetically equalized between the initiators of TNFi and MTX monotherapy at a constant value. Estimates were given on the hazard ratio scale. We identified 5764 initiators of TNFi and 3588 initiators of MTX monotherapy. TNFi initiators were younger (58 vs. 64 years) with a shorter disease duration. Our total effect estimates (TNFi vs. MTX [reference]) were protective in direction (0.76-0.91). The NDE estimate was 0.76 [95% confidence interval (CI) 0.59, 0.98], whereas the NIE estimate was 1.00 [95%CI 1.00, 1.00]. In the CDE analyses accounting for longitudinal CDAI, the CDE estimates was 1.27 [95%CI 0.60, 2.69]. We could not convincingly demonstrate a direct benefit of TNFi outside its impact on CDAI. At present, the emphasis should be on the stringent control of RA disease activity, a known important CV risk factor, regardless of medication choice.

Association Between Rheumatoid Arthritis Disease Activity and Periodontitis Defined by Tooth Loss: Longitudinal and Cross-Sectional Data From Two Observational Studies.

To analyze the effect of tooth loss/periodontitis on disease activity in early and established rheumatoid arthritis (RA). Participants of the Course And Prognosis of Early Arthritis (CAPEA) early arthritis cohort reported their number of teeth at baseline. The number of teeth had been validated as a predictor of periodontitis. Clinical end points, including disease activity score (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [ESR]), swollen joint count (SJC), ESR, and C-reactive protein level were collected at baseline, 3, 6, 12, 18, and 24 months. We used linear mixed regression models to estimate the association between tooth loss and clinical end points over time in early arthritis. For established RA, we analyzed cross-sectional data from the German National Database (NDB). All models accounted for age, sex, smoking, seropositivity, education level, and disease duration (only NDB). Among 1,124 CAPEA participants with early arthritis, those with higher tooth loss were older, more often male, smokers, and seropositive, and they had higher disease activity and inflammation markers at baseline. Tooth loss was associated with higher disease activity and ESR values over time. Inflammatory markers decreased comparably across tooth loss categories. Glucocorticoid use was higher among those with more tooth loss, whereas dose reduction was similar across tooth loss categories. Among 7,179 NDB participants with longstanding RA, disease activity and inflammation markers but not SJC were significantly higher in patients with more tooth loss. Although we observed an association between tooth loss and disease activity scores and inflammation markers in early and established RA, longitudinal results suggest that tooth loss does not hamper treatment response.

Machine Learning Applied to Patient-Reported Outcomes to Classify Physician-Derived Measures of Rheumatoid Arthritis Disease Activity.

Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated. Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data. A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%. ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are.

Autonomous motivation to reduce sedentary behaviour is associated with less sedentary time and improved health outcomes in rheumatoid arthritis: a longitudinal study

BackgroundThis longitudinal study investigated whether changes in autonomous and controlled motivation to reduce sedentary behaviour were associated with variability in sedentary, standing and stepping time and, in turn, disease activity, systemic inflammation, pain and fatigue in rheumatoid arthritis (RA).MethodsPeople with RA undertook assessments at baseline (T1, n = 104) and 6 months follow-up (T2, n = 54) to determine autonomous and controlled motivation to reduce sedentary behaviour (Behavioural Regulation in Exercise Questionnaire-2), free-living sedentary, standing and stepping time (7 days activPAL3μ wear), Disease Activity Score-28 (DAS-28), systemic inflammation (c-reactive protein [CRP]), pain (McGill Pain Questionnaire) and fatigue (Multidimensional Assessment of Fatigue Scale). N = 52 participants provided complete data at T1 and T2. Statistical analyses: In a series of models (A and B), path analyses examined sequential associations between autonomous and controlled motivation to reduce sedentary behaviour with activPAL3μ-assessed behaviours and, in turn, RA outcomes.ResultsModels demonstrated good fit to the data. Model A (sedentary and stepping time): autonomous motivation was significantly negatively associated with sedentary time and significantly positively related to stepping time. In turn, sedentary time was significantly positively associated with CRP and pain. Stepping time was not significantly associated with any health outcomes. Model B (standing time): autonomous motivation was significantly positively associated with standing time. In turn, standing time was significantly negatively related to CRP, pain and fatigue.ConclusionsAutonomous motivation to reduce sedentary behaviour is associated with sedentary and standing time in RA which may, in turn, hold implications for health outcomes.

Increased prevalence of Staphylococcus aureus nasal carriage in rheumatoid arthritis patients with moderate/high disease activity

BackgroundStaphylococcus aureus (S. aureus) nasal carriage is a well-known risk factor for surgical site infection (SSI) after total joint arthroplasty. This study aimed to compare the prevalence of S. aureus nasal carriage between patients with osteoarthritis (OA), a degenerative joint disease, and those with rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, who underwent total joint arthroplasty, and to investigate the influence of RA disease activity on nasal carriage rate. MethodsThis retrospective study targeted 508 OA and 107 RA patients who underwent S. aureus nasal screening prior to primary total knee and/or hip arthroplasty. RA patients were divided into two groups based on disease activity: the remission/low disease activity (REM/LDA) group and the moderate/high disease activity (MDA/HDA) group. Factors associated with S. aureus nasal carriage were assessed with multivariate logistic regression models. ResultsOf all 615 patients, 155 (25%) carried S. aureus in their nares. Compared to OA patients, RA patients had a significantly higher rate of S. aureus nasal carriage (24% vs. 33%, p = 0.049). Compared to the REM/LDA group (n = 39), the MDA/HDA group (n = 58) had a significantly higher rate of S. aureus nasal carriage (21% vs. 41%, p = 0.032). Multivariate analysis revealed that the MDA/HDA group, but not the REM/LDA group, had a significantly higher odds of S. aureus nasal carriage compared to the OA group (odds ratio: 2.76, 95% confidence interval: 1.07–7.12). ConclusionPreoperative nasal screening for S. aureus is beneficial, especially in RA patients with moderate/high disease activity.