Comorbidities In Rheumatoid Arthritis Research Articles

Geographic Socioeconomic Influences on Disease Activity in Rheumatoid Arthritis in an Academic and Safety Net Hospital System.

The objective of this study was to analyze the impact of the Area Deprivation Index (ADI) on disease activity and cardiovascular comorbidity in rheumatoid arthritis (RA). A retrospective analysis of adult patients with RA was conducted to highlight differences in academic and safety net hospital clinics. Demographics, RA medication history, patient portal engagement, primary care presence, emergency or inpatient visits, RA disease activity and functional scores, Charlson Comorbidity Index (CCI), and cardiovascular disease (CVD) presence were captured. The ADI rank was assigned using nine-digit zip codes. Patients were stratified by the upper versus lower ADI decile group and matched by age, sex, race, ethnicity, insurance, and CCI using propensity score analysis. Patients with RA from the academic practice (n = 542) and the safety net hospital (n = 496) were assessed. In the academic cohort, those with high ADI scores (>8, more deprivation) had higher RA disease activity scores (Routine Assessment of Patient Index Data 3 mean ± SD: high 13.83 ± 6.94 vs low 11.17 ± 7.37, P < 0.0001; Clinical Disease Activity Index mean ± SD: high 11.97 ± 11.74 vs low 9.40 ± 7.97, P < 0.05), more functional impairment (Multidimensional Health Assessment Questionnaire mean ± SD: high 2.99 ± 2.29 vs low 2.34 ± 2.23, P < 0.01), lower MyChart use (P < 0.001), and different smoking history (P < 0.01) compared to those with low ADI scores (<3, less deprivation). In the safety net cohort, there was a statistically significant difference only in smoking status (P < 0.05). CVD was not significantly different in either cohort. The absence of differences in RA disease activity and functional impairment in patients suggests that the ADI may not be as effective at predicting RA disease activity specifically in a safety net health care context. Identifying the discrepancies between the two systems may elucidate areas of improvement for patient care.

The kynurenine pathway in patients with rheumatoid arthritis during tumor necrosis factor α inhibitors treatment.

The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis (RA). The aim of the study was to evaluate the effect of treatment with tumor necrosis factor α (TNF-α) inhibitors on the activity of the kynurenine pathway in patients with RA. This was an investigator-initiated, prospective, observational study. The study was performed on 30 RA patients (Caucasian, 11 male, 19 female; mean age 45 ±16 years) treated with TNF-α inhibitors. All patients were assessed before and after 6 months of therapy. As a control group, age- and sex-matched, 20 healthy volunteers were recruited. Disease activity was evaluated by the Modified Disease Activity Score with 28-joint count (DAS28). Inflammatory markers were assessed routinely by the hospital central laboratory. Serum concentrations of kynurenine, serotonin and tryptophan were measured with specific immunoassays. To estimate indoleamine 2,3-dioxygenase (IDO) activity, kynurenine-to-tryptophan ratio was calculated. The results of our study showed changes in tryptophan metabolism in RA patients, compared with healthy controls. Surprisingly, RA patients had statistically significant decreased kynurenine-to-tryptophan ratio (p = 0.003), which could indicate diminished IDO activation in RA. Moreover, we found no significant changes in kynurenine-to-tryptophan ratio after treated with TNF-α inhibitors (p = 0.490), despite disease remission. Additionally, tryptophan metabolism activity did not correlate with objective markers of inflammation. The RA patients had altered tryptophan metabolism, compared with healthy controls. The mechanisms affecting tryptophan metabolism in RA may be complex. We believe that continuing elucidation of pathophysiological pathways relevant in RA offer substantial hope for the development of specific pharmacotherapy for treatment of RA - especially for comorbidity of RA and depression.

Disease activity of rheumatoid arthritis and kidney function decline: a large prospective registry study

IntroductionChronic kidney disease (CKD) is a common comorbidity of rheumatoid arthritis (RA). The association of longitudinal RA disease activity with long-term kidney function has remained uncertain.MethodWe analysed a multicentre prospective...

Disease and treatment-related comorbidities in rheumatoid arthritis

Disease and treatment-related comorbidities in rheumatoid arthritis

γδT Cells Induce the Inflammatory Response of Human Fibroblast-Like Synoviocytes Directly or by Stimulating B Cells to Activate IL-17/STAT3 Signaling Pathway

Introduction: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. Methods: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1β, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. Results: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1β, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1β and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1β and TNF-α were also decreased significantly. Conclusion: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.

Analysis of potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression immunologic indicators

ObjectiveDepression can impact the severity of rheumatoid arthritis (RA). This study aimed to investigate the relationship between Th1, Th2, Th17, Treg cell subsets, and their associated cytokines (e.g., IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α), and the occurrence of RA both with and without comorbid depression. The objective is to identify potential biological markers, therapeutic targets, and the therapeutic effects of RA with comorbid depression. Results53 RA patients,46 RA with comorbid depression patients and 51 healthy subjects were included in the RA,RD and HC group from August 2021 and October 2022. Among RA patients, 46.46 % were comorbid with depression. IL-6 concentrations were significantly higher in RD group than in RA group.Comparison between the HC and RA and RD groups revealed that Th1 %, Th17 %, Th1, Th17, Th1/Th2, Th17/Treg and Th1/Treg were significantly higher in the RA and RD groups, and conversely, Th2 %, Treg%, Th2 and Treg were significantly lower than in the HC group.The RA group compared to the RD group found that Th17 %, Th17 and Th17/Treg were significantly higher in the RD group than in the RA group, however, Th1 %, Treg and Th2/Treg were significantly lower than in the RA group. The total HAMD score had a medium strength positive correlation with IL-6. ConclusionThese findings suggest that elevated the autoimmunity status was overactivated in RA with or without depression activates patients, IL-6 may be a predictor of the severity of RA with comorbid depression, IL-6 concentrations and an imbalance in the Th17/Treg may underlie the comorbidity of RA and depression, offering potential targets for therapeutic intervention, prompting further evaluation of the role of indirect inflammatory markers in RA with comorbid depression, highlighting the need for additional research to clarify the complex relationship between inflammation and psychological health.

Rheumatoid Arthritis and Risk of Depression in South Korea

Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. To investigate the risk of depression following RA diagnosis among patients in South Korea. This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Newly diagnosed depression (ICD-10 codes F32 or F33). The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Redefining comorbidity understanding in rheumatoid arthritis through novel approaches using real-world data

Rheumatoid arthritis (RA) is a prevalent chronic disease that is associated with numerous comorbidities. Accurate assessment of these coexisting conditions, as reported by clinicians, is critical for an improved understanding of the impact of the disease and patient care. This perspective aims to evaluate the utility of real-world data (RWD) for enhancing the understanding of comorbidities in RA and to assess its potential in reshaping clinical management. RWD approaches, specifically the use of structured databases or data extracted from electronic health records, offer promising alternatives to overcome the limitations of traditional methodologies. Structured databases provide a systematic approach to data analysis, utilizing diagnosis codes to study large patient cohorts, revealing the prevalence of conditions, and demonstrating the potential for long-term disease trend analysis. Meanwhile, natural language processing (NLP) and artificial intelligence (AI) image analysis can bridge the gap between structured and unstructured data, by extracting meaningful information from unstructured fields such as free text or imaging. NLP has proven effective in the identification of RA patients and research outcomes, while AI image analysis has enabled the discovery of hidden findings in cardiovascular assessments, establishing a basis for the assessment of comorbidities in RA. However, while the benefits of using RWD are substantial, challenges remain. Ensuring comprehensive data capture, managing missing data, and improving data detection are key areas requiring attention. The involvement of clinicians and researchers in rheumatology is crucial in unlocking the potential of RWD studies, offering the promise of significant improvements in disease characterization and patient health outcomes.

A stronger association of depression with rheumatoid arthritis in presence of obesity and hypertriglyceridemia.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic and systemic inflammation. Recent research underscores the role of chronic inflammation in multiple common RA comorbidities such as depression, obesity, and cardiovascular diseases (CVDs), suggesting a potential overlap of the pathogenic mechanisms for RA. However, it is not well understood how the coexistence of these comorbid conditions impacts the risk of RA and whether any such association relates to body's inflammatory state. We used data from the 2007-2010 United States National Health and Nutrition Examination Survey (NHANES) database and compared RA prevalence between subsamples with the presence of any two conditions among depression, obesity, and hypertriglyceridemia (HTG). Each subsample was further divided into three categories based on the serum level of the inflammatory marker C-reactive protein (CRP) and analyzed for statistically significant differences using three-way χ2 tests of independence. The study was conducted on 4,136 patients who fulfilled the inclusion criteria (representing 163,540,241 individuals after adjustment for sampling weights). Rates of depression, obesity, and HTG were found to be significantly higher (P < 0.001) among the subjects with RA compared with the control population with no arthritis. The presence of depression along with obesity or HTG showed a noticeably higher RA prevalence but such an association was not observed for the combination of obesity and HTG. The synergistic effect of HTG with depression was found to be most prominent at a medium CRP level (1-3 mg/L), while for obesity, the effect was observed across all CRP levels examined. These findings were further confirmed by the three-way χ2 test for independence. The presence of obesity or HTG in subjects suffering from depression might pose an increased risk of RA. Inflammatory mechanisms potentially play an important underlying role as suggested by the strong dependency of the association to CRP level. Identification of synergistic associations between RA risk conditions could provide useful information to predict the development and progress of RA.

Comorbidities and chance of remission in patients with early rheumatoid arthritis receiving methotrexate as first-line therapy: a Swedish observational nationwide study

ObjectivesThis study aims to examine whether comorbidities affect the likelihood of reaching primary remission on methotrexate monotherapy as the first disease-modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA).MethodsWe used...

Association of serum chemerin levels with complications and comorbidity in rheumatoid arthritis

Introduction. Rheumatoid arthritis (RA) is a systemic autoimmune disease as well as a typical inflammatory process. Chemerin is a fat tissue cytokine, which specific receptors were discovered on the surface of the innate immune cells. It is of interest to study the association of chemerin with the complications and comorbidity in RA.Aim. To study the association between serum chemerin levels with complications and comorbidity in rheumatoid arthritis.Materials and methods. 88 women with RA were enrolled in our study. ll patients undergone standard clinical and laboratory examination. Serum chemerin, high-sensitive C-reactive protein (hsCRP), anti-citrullinated protein antibodies, insulin and C-peptide levels were determined using ELISA. X-ray absorptiometry was performed. Statistical analysis was performed using conventional methods with a software package Statistica 10.0.Results. Median chemerin concentration was 463.5 [366–576.5] ng/ml. Chemerin concentration correlated with the age (ρ = 0.232; р = 0.030), weight (ρ = 0.254; р = 0.017) and body mass index (BMI) (ρ = 0.212; р = 0.047), but wasn’t associated with the RA classification criteria. Positive correlation between chemerin concentration and number of painful joints (NPJ) (ρ = 0.213; р = 0.046) and hsCRP (ρ = 0.273; р = 0.010) was observed. Patients with type 2 diabetes mellitus (DM2) had higher chemerin concentration (598.0 ng/ml vs 479.5 ng/ml, Z = -2.68; p = 0.007) and patients with cholecystectomy in anamesis had lower (359.0 ng/ml vs 479.0 ng/ml, Z = 2.02; p = 0.043). Chemerin concentration correlated with systolic and diastolic blood pressure (BP) (ρ = -0.41; р &lt; 0.001 and ρ = -0.27; р = 0.028, respectively).Conclusions. Chemerin concentration in women with RA correlates with age, weight, BMI, NPJ and hsCRP. Chemerin concentration in patients with comorbid DM2 was higher and in patients comorbid with cholecystectomy in anamnesis was lower. Chemerin concentration correlates negatively with a systolic and diastolic BP.

Associations between Rheumatoid Arthritis and Various Comorbid Conditions in Germany—A Retrospective Cohort Study

Aims: The aim of the present study was to estimate the prevalence of physical and mental health comorbidities in patients with rheumatoid arthritis (RA) in Germany, in order to better understand the complex clinical picture and its consequences. Methods: This retrospective cohort study was based on data from the IQVIA Disease Analyzer database and included individuals aged ≥ 16 years with an initial documented diagnosis of RA between 2015 and 2021 (index date). RA patients were matched 1:1 with non-RA individuals using nearest neighbor propensity score matching. The study investigated associations between RA and various disorders documented within 365 days after the index date. The cumulative incidence of defined disorders was calculated for individuals with and without RA. Multivariable logistic regression models were used to study these associations. Results: Data were available for a total of 49,713 patients with and 49,713 patients without RA (mean age: 60.4 (SD: 15.5) years; 66.7% female). A significant and clinically relevant positive association was observed between RA and seven disorders: soft tissue disorders (Odds Ratio (OR): 1.47; 95% Confidence Interval (CI): 1.42–1.52), renal failure (OR: 1.36; 95% CI: 1.26–1.47), anemia (OR: 1.32; 95% CI: 1.24–1.40), liver diseases (OR: 1.32, 95% CI: 1.23–1.41), osteopathies and chondropathies (OR: 1.28; 95% CI: 1.22–1.3), diseases of the esophagus, stomach and duodenum (OR: 1.18; 95% CI: 1.14–1.22), and nutritional deficiencies (OR: 1.17; 95% CI: 1.10–1.24). Conclusions: We observed significant associations between RA and several comorbidities, which have clinical relevance for the care of RA patients not only in general practices but also in specialist settings.

Assessing clusters of comorbidities in rheumatoid arthritis: a machine learning approach

BackgroundComorbid conditions are very common in rheumatoid arthritis (RA) and several prior studies have clustered them using machine learning (ML). We applied various ML algorithms to compare the clusters of comorbidities derived and to assess the value of the clusters for predicting future clinical outcomes.MethodsA large US-based RA registry, CorEvitas, was used to identify patients for the analysis. We assessed the presence of 24 comorbidities, and ML was used to derive clusters of patients with given comorbidities. K-mode, K-mean, regression-based, and hierarchical clustering were used. To assess the value of these clusters, we compared clusters across different ML algorithms in clinical outcome models predicting clinical disease activity index (CDAI) and health assessment questionnaire (HAQ-DI). We used data from the first 3 years of the 6-year study period to derive clusters and assess time-averaged values for CDAI and HAQ-DI during the latter 3 years. Model fit was assessed via adjusted R2 and root mean square error for a series of models that included clusters from ML clustering and each of the 24 comorbidities separately.Results11,883 patients with RA were included who had longitudinal data over 6 years. At baseline, patients were on average 59 (SD 12) years of age, 77% were women, CDAI was 11.3 (SD 11.9, moderate disease activity), HAQ-DI was 0.32 (SD 0.42), and disease duration was 10.8 (SD 9.9) years. During the 6 years of follow-up, the percentage of patients with various comorbidities increased. Using five clusters produced by each of the ML algorithms, multivariable regression models with time-averaged CDAI as an outcome found that the ML-derived comorbidity clusters produced similarly strong models as models with each of the 24 separate comorbidities entered individually. The same patterns were observed for HAQ-DI.ConclusionsClustering comorbidities using ML algorithms is not computationally complex but often results in clusters that are difficult to interpret from a clinical standpoint. While ML clustering is useful for modeling multi-omics, using clusters to predict clinical outcomes produces models with a similar fit as those with individual comorbidities.

Are diet and exercise associated with depression in rheumatoid arthritis patients?

Abstract Background Although depression is a common comorbidity of rheumatoid arthritis (RA), little is known about a potential treatment strategy. Current studies of dietary improvement for depression have recently emerged in the general population, but have hardly any coverage in RA. Also, less exercise increases the number of people experiencing depression, and current studies showed that most RA patients are physically inactive. Thus, our study aimed to identify the potential factors associated with depression in RA patients. Methods We included 157 RA patients (84.7% female; mean age 56.43±13.9 years; mean disease duration 19.53±9.54 years). All participants completed the General Health Questionnaire - 28, the Visual Analogue Scale Pain, the 36-item Short Form Health Survey, the Physical Activity Scale, and the Food Frequency Questionnaire. Correlations and multiple linear regressions were used to analyse the data. Results Bivariate analyses showed a significant association between disease activity (.25; p ≤ 0.01), functional disability (.22; p ≤ 0.01), pain (.35; p ≤ 0.001), fatigue (-.45; p ≤ 0.001), physical inactivity (-.19; p ≤ 0.05), frequent consumption of fried foods (-.22; p ≤ 0.01) and depression. No other foods were associated with depression in RA. The multiple regression analyses showed that disease activity, fatigue, and fried foods consumption were significantly associated with depression in the final model. However, the association between physical activity and depression was no longer significant using multivariate models. Explained variance in the final regression model was 27.6%. Conclusions It appears that frequent consumption of fried foods is associated with depression in RA when controlled for sociodemographic and clinical variables. Further research on specific dietary habits and underlying mechanisms in the gut-brain axis may help to develop treatment options for the prevention of psychological distress in RA. (Grant: VEGA: 1/0748/22; APVV-15-0719) Key messages • Non-pharmacological intervention for reducing depression should target the patient's diet. • Frequent consumption of fried food may influence depression more significantly than physical inactivity.

Integrating Chinese Herbal Medicine into Conventional Care Was Related to Lower Risk of Sarcopenia Among Rheumatid Arthritis Patients: A Retrospective, Population-Based Study.

Sarcopenia is a frequently observed comorbidity of rheumatoid arthritis (RA) due to the chronic activation of the innate immune system. Accumulating evidence has indicated that Chinese herbal medicine (CHM) safely suppresses proinflammatory pathways and controls inflammation-associated disease, but its effect in reducing the risk of developing sarcopenia among RA subjects has not been established. We conducted a population-level cohort study to compare the sarcopenia risk in patients with RA who use or do not use CHM. Using claims from a nationwide insurance database, we recruited patients with newly diagnosed RA and without sarcopenia between 2002 and 2010. Propensity score matching was applied to randomly select sets of CHM users and non-CHM users to compare the sarcopenia risk until the end of 2013. The risk of new-onset sarcopenia was assessed using the Cox proportional hazards model. As compared to non-CHM users, those receiving CHM treatment had a lower incidence of sarcopenia (7.69 vs 9.83 per 1000 person-years). CHM was correlated with a decreased chance of sarcopenia after controlling for potential covariates. Notably, use of CHM for more than two years may diminish the risk of getting sarcopenia by about 47% when taken as prescribed. Prescriptions of several herbal formulae may benefit the reduction of sarcopenia risk, such as Yan-Hu-Suo, Bei-Mu, Da-Huang, Huang Qin, Ping-Wei-San (PWS), Shu-Jing-Huo-Xue-Tang (SJHXT) and Chuan-Xiong-Cha-Tiao-San (CXCTS). This study produced new evidence as it is the first to show that the longer duration of CHM use was correlated to reduced risk of sarcopenia in a dose-dependent manner, implying that CHM treatment could be embraced as a routine care strategy for preventing sarcopenia.

Inflammatory Cytokines in Rheumatoid Arthritis: Diagnostic Challenges, Pathogenic Mechanisms and their Role in Depression and Management.

Depression being a common comorbidity of rheumatoid arthritis (RA) is found to be responsible for the reduction in the lifespan of the sufferer along with the compromised quality of life. The study quoted below highlights the pathogenic pathways, the frequency of RA along with its impact on patients, thus, raising awareness about the concerned topic. It is found that the chances and frequency of developing depression are 2-3 times higher in patients with RA in comparison to the general population. For such studies, self-reported questionnaires along with proper screening of inclusion and exclusion criteria have been employed which helped in a better comparative study of the topic. As per a report from a meta-analysis, 16.8% of patients with RA have been observed to develop severe depression. According to recent research in the related field, the hypothesis of the role of immune-mediated processes and their role in brain networks and inflammation has been found to be engaged in the progression and pathophysiology of depression in patients with RA. Autoimmune mechanisms and cytokines are found to play an essential role in coordination for initiating and sustaining the disorder. Involvement of IL-1, IL-6 and TNF-α has been studied and analysed widely. A number of studies have shown a connection between depression and RA-related physical impairment, fatigue, and increased pain. Higher mortality, reduced treatment compliance, and more comorbidities effects increased suicide risk. It is also found that depression along with RA leads to hospitalizations, which in turn increase the cost of care for the patient. Hence, it could be stated that the study of depression in RA can be an important marker for the progression of RA and its prognosis. The latest treatment strategies for RA include management of symptoms and early disorder treatment The current review aims to investigate and bring the links between RA and its symptoms into the limelight, including the psycho-social, physiological, and neurological aspects along with their molecular mechanism, for a better discernment of the topic for the readers.

Disparities in multimorbidity and comorbidities in rheumatoid arthritis by sex across the lifespan.

Multimorbidity is burdensome for people with RA. We investigated differences in multimorbidity and comorbidities by sex and age in the RA population. This cross-sectional analysis used national administrative claims (OptumLabs® Data Warehouse) from people with RA and non-RA comparators (matched on age, sex, race, census region, index year and length of baseline insurance coverage) from 2010-2019. RA was determined using a validated algorithm. Multimorbidity was defined as ≥2 (MM2+) or ≥5 (MM5+) comorbidities from a validated set of 44 chronic conditions. We used logistic regression to assess associations between characteristics and multimorbidity. The sample included 154 391 RA patients and 154 391 non-RA comparators. For people aged 18-50 years, RA women (vs RA men) had 7.5 and 4.4 (vs 3.2 and 0.9 in non-RA women vs non-RA men) percentage point increases for MM2+ and MM5+, respectively. For people aged 51+ years, RA women (vs RA men) had 2.1 and 2.5 (vs 1.2 and 0.3 in non-RA women vs non-RA men) percentage point increases for MM2+ and MM5+, respectively. Interactions revealed that differences in multimorbidity between women and men were exacerbated by RA (vs non-RA) (P < 0.05), with more pronounced effects in people aged 18-50. Men had more cardiovascular-related conditions, whereas RA women had more psychological, neurological and general musculoskeletal conditions. Other comorbidities varied by sex and age. Multimorbidity disproportionately impacts women with RA. Research, clinical and policy agendas for rheumatic diseases should acknowledge and support the variation in care needs by sex and gender across the lifespan.

Effects of Tofacitinib on Muscle Remodeling in Experimental Rheumatoid Sarcopenia.

Sarcopenia is a frequent comorbidity of rheumatoid arthritis (RA). Clinical trials have shown that JAK inhibitors (JAKi) produce an asymptomatic increase in serum creatine kinase (CK) in RA, suggesting an impact on muscle. We evaluated the effect of JAKi in muscle remodeling in an experimental RA model. Antigen-induced arthritis (experimental RA, e-RA) was performed in 14 rabbits. Seven rabbits received tofacitinib (TOFA, orally 10 mg/kg/day). Animals were euthanized one day after the last ovalbumin injection, and muscles were prepared for histology, RT-PCR, and WB. C-reactive protein (CRP) and Myostatin (MSTN) serum concentration were determined by ELISA. Creatine and creatine kinase (CK) were analyzed. An increase in body weight as well as tibialis anterior cross-sectional area and diameter was observed in e-RA+TOFA vs. e-RA. e-RA decreased type II fibers and increased the myonuclei number, with all reverted by TOFA. TOFA did not modify CRP levels, neither did MSTN. TOFA significantly reduced IL-6, atrogin-1, and MuRF-1 compared with e-RA. e-RA+TOFA showed higher CK and lower creatine levels compared with e-RA. No differences in PAX-7 were found, while TOFA prevented the increase in MyoD1 in e-RA. Our model reflects the features of rheumatoid sarcopenia in RA. JAKi increased muscle mass through attenuating IL-6/JAK/STAT activation, decreasing atrogenes, and restoring muscle differentiation markers. These data together with an increase in CK support the role of CK as a valuable marker of muscle gain following JAKi treatment.

Hemodynamic effects of antihypertensive therapy in patients with hypertension and rheumatoid arthritis comorbidity

Hemodynamic effects of antihypertensive therapy in patients with hypertension and rheumatoid arthritis comorbidity

Are comorbidities associated with the cytokine/chemokine profile of persistent apical periodontitis?

This study aimed to identify disease-related markers in persistent apical periodontitis (PAP) biopsies and examine whether these were associated with comorbidities like rheumatoid arthritis (RA) and cardiovascular diseases (CVD). The levels of the cytokines/chemokines GM-CSF, IFN-γ, IL-2, IL-6, IL-9, IL-10, IL-13, IL-15, IL-17E/IL-25, IL-21, IL-23, IL-27, IL-28A/IFN -λ2, IL-33, MIP-3α/CCL20, and TNF-α were determined in lesions from patients with PAP (n = 20) and compared to healthy bone samples (n = 20). We identified eleven cytokines to be differently expressed, and among them, IL-2, IL-6, IL-17E, IL-21, and IL-27 appeared to drive the discrepancy between the disease and healthy groups. The levels of T follicular helper (Tfh) cell promoting cytokines (IL-21, IL-6, IL-27) were enhanced while T helper (Th) 1 cell promoting cytokine (IL-2), Th2 cell promoting cytokine (IL-13), and Th17 cell promoting cytokine (IL-17E) were reduced in the PAP group. The data also indicate that Tfh cell differentiation (IL-21), along with Th1 (GM-CSF, IFNγ), Th2 (IL-13), and Th17 (GM-CSF) cell differentiation, might be increased in the subpopulation of patients suffering from RA, whereas no differences were found in patients with CVD. Levels of cytokines/chemokines in PAP were identified, and cluster analyzes indicated that these markers may be associated with the differentiation of different T cell populations. Patients with PAP and RA comorbidities showed elevated levels of markers reinforcing this association. Molecular analyses of PAP may result in identification of prognostic markers.