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Objective. Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. This study aimed to examine how different diagnostic dementia definitions perform in patients with RA compared to individuals without RA. Methods. The study population included 2050 individuals (1025 with RA) from a retrospective, population-based cohort in southern Minnesota and compared the performance of 3 code-based dementia diagnostic algorithms with medical record review diagnosis of dementia. For the overall comparison, each patient’s complete medical history was used, with no time frames. Sensitivity analyses were performed using 1-, 2-, and 5-year windows around the date that dementia was identified in the medical record (reference standard). Results. Algorithms performed very similarly in persons with and without RA. The algorithms generally had high specificity, negative predictive values, and accuracy, regardless of the time window studied (> 88%). Sensitivity and positive predictive values varied depending on the algorithm and the time window. Sensitivity values ranged 56.5-95.9%, and positive predictive values ranged 55.2-83.1%. Performance measures declined with more restrictive time windows. Conclusion. Routinely collected electronic health record (EHR) data were used to define code-based dementia diagnostic algorithms with good performance (vs diagnosis by medical record review). These results can inform future studies that use retrospective databases, especially in the same or a similar EHR infrastructure, to identify dementia in individuals with RA. [ABSTRACT FROM AUTHOR]

Objective. The World Health Organization fracture risk assessment tool (FRAX) algorithm for risk prediction of major osteoporotic and hip fractures accounts for several risk factors, including rheumatoid arthritis (RA), since individuals with RA have an excess burden of fractures. FRAX has not been validated in population-based RA cohorts in the US. We aimed to determine the accuracy of FRAX predictions for individuals with RA in the US. Methods. This retrospective population-based cohort study included residents of Olmsted County, Minnesota, who were followed until death, migration, or last medical record review. Each patient with RA (1987 American College of Rheumatology criteria met in 1980-2007, age 40-89 years) was matched 1:1 on age and sex to an individual without RA from the same underlying population. Ten-year predictions for major osteoporotic and hip fractures were estimated using the FRAX tool. Fractures were ascertained through follow-up, truncated at 10 years. Standardized incidence ratios (SIRs) and 95% CI were calculated to compare observed and predicted fractures. Results. The study included 662 patients with RA and 658 non-RA comparators (66.8% vs 66.9% female and a mean age of 60.6 vs 60.5 years, respectively). Among patients with RA, 76 major osteoporotic fractures and 21 hip fractures were observed during follow-up (median follow-up: 9.0 years) compared to 67.0 predicted major osteoporotic fractures (SIR 1.13, 95% CI 0.91-1.42) and 23.3 predicted hip fractures (SIR 0.90, 95% CI 0.59-1.38). The observed and predicted major osteoporotic and hip fracture risks were similar for patients with RA and non-RA comparators. Conclusion. The FRAX tool is an accurate method for estimating major osteoporotic and hip fracture risk in patients with RA. [ABSTRACT FROM AUTHOR]

Objective. To assess trends in the incidence of heart failure (HF) in patients with incident rheumatoid arthritis (RA) from 1980 to 2009 and to compare different HF definitions in RA. Methods. The study population comprised Olmsted County, Minnesota residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009). All subjects were followed until death, migration, or April 30, 2019. Incident HF events were defined as follows: (1) meeting the Framingham criteria for HF, (2) diagnosis of HF (outpatient or inpatient) by a physician, or (3) International Classification of Diseases, 9th revision (ICD-9), or ICD, 10th revision (ICD-10), codes for HF. Patients with HF prior to the RA incidence/index date were excluded. Cox proportional hazards models were used to compare incident HF events by decade, adjusting for age, sex, and cardiovascular risk factors. HF definitions 2 and 3 were compared to the Framingham criteria. Results. The study included 905 patients with RA (mean age 55.9 years; 68.6% female; median follow-up 13.4 years). The 10-year cumulative incidence of HF events by any chart-reviewed method in the RA cohort in the 1980s was 11.66% (95% CI 7.86-17.29), in the 1990s it was 12.64% (95% CI 9.31-17.17), and in the 2000s it was 7.67% (95% CI 5.36-10.97). The incidence of HF did not change across the decades of RA incidence using any of the HF definitions. Physician diagnosis of HF and ICD-9/10 code-based definitions of HF performed well compared to the Framingham criteria, showing moderate to high sensitivity and specificity. Conclusion. The incidence of HF in patients with incident RA in the 2000s vs the 1980s was not statistically significantly different. Physician diagnosis of HF and ICD-9/10 codes for HF performed well against the Framingham criteria. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA−), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA− RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA− RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA− RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA− RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA− RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients' ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics. [ABSTRACT FROM AUTHOR]

Objective. Growing evidence suggests that patients with rheumatoid arthritis (RA) have increased risk for dementia. We assessed risk factors for incident dementia in an inception cohort of patients with RA. Methods. This retrospective population-based cohort study included residents of 8 counties in Minnesota who were = 50 years of age when they met 1987 American College of Rheumatology criteria for incident RA between 1980 and 2014 and were followed until death/migration or December 31, 2019. Patients with dementia before RA incidence were excluded. Incident dementia was defined as 2 relevant International Classification of Diseases, 9th or 10th revision codes at least 30 days apart. Data on sociodemographics, disease characteristics, cardiovascular/cerebrovascular disease (CVD) risk factors, and comorbidities were abstracted from medical records. Results. The study included 886 patients with RA (mean age 65.1 yrs, 65.2% female). During the follow-up period (median 8.5 yrs), 103 patients developed dementia. After adjusting for age, sex, and calendar year of RA incidence, older age at RA incidence (HR 1.14 per 1 year increase, 95% CI 1.12-1.17), rheumatoid nodules (HR 1.76, 95% CI 1.05-2.95), hypertension (HR 1.84, 95% CI 1.19-2.85), presence of large joint swelling (HR 2.03, 95% CI 1.14-3.60), any CVD (HR 2.25, 95% CI 1.38-3.66), particularly ischemic stroke (HR 3.16, 95% CI 1.84-5.43) and heart failure (HR 1.82, 95% CI 1.10-3.00), anxiety (HR 1.86, 95% CI 1.16-2.97), and depression (HR 2.63, 95% CI 1.76-3.93) were associated with increased risk of dementia. After adjusting for CVD risk factors and any CVD, all covariates listed above were still significantly associated with risk of dementia. Conclusion. Apart from age, hypertension, depression, and anxiety, all of which are universally recognized risk factors for dementia, clinically active RA and presence of CVD were associated with an elevated risk of dementia incidence among patients with RA. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggested that dementia risk in patients with rheumatoid arthritis (RA) is higher than in the general population.Objective: To examine the associations of RA with cognitive decline and dementia, and neuroimaging biomarkers of aging, Alzheimer's disease, and vascular pathology in adult participants in the Mayo Clinic Study of Aging (MCSA).Methods: Participants with RA were matched 1:3 on age, sex, education, and baseline cognitive diagnosis to participants without RA. RA cases with MRI were also matched with non-cases with available MRI. All available imaging studies (i.e., amyloid and FDG PET, sMRI, and FLAIR) were included. The study included 104 participants with RA and 312 without RA (mean age (standard deviation, SD) 75.0 (10.4) years, 33% male and average follow-up (SD) 4.2 (3.8) years).Results: Groups were similar in cognitive decline and risk of incident dementia. Among participants with neuroimaging, participants with RA (n = 33) and without RA (n = 98) had similar amyloid burden and neurodegeneration measures, including regions sensitive to aging and dementia, but greater mean white matter hyperintensity volume relative to the total intracranial volume (mean (SD)% : 1.12 (0.57)% versus 0.76 (0.69)% of TIV, p = 0.01), and had higher mean (SD) number of cortical infarctions (0.24 (0.44) versus 0.05 (0.33), p = 0.02).Conclusion: Although cognitive decline and dementia risk were similar in participants with and without RA, participants with RA had more abnormal cerebrovascular pathology on neuroimaging. Future studies should examine the mechanisms underlying these changes and potential implications for prognostication and prevention of cognitive decline in RA. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether specific respiratory tract diseases are associated with increased rheumatoid arthritis (RA) risk.Methods: This case-control study within the Mass General Brigham Biobank matched newly diagnosed RA cases to 3 controls on age, sex, and electronic health record history. We identified RA using a validated algorithm and confirmed by medical record review. Respiratory tract disease exposure required 1 inpatient or 2 outpatient codes at least 2 years before the index date of RA clinical diagnosis or matched date. Logistic regression models calculated ORs for RA with 95% CIs, adjusting for confounders. We then stratified by serostatus ("seropositive" was positive rheumatoid factor and/or anticitrullinated protein antibodies) and smoking.Results: We identified 741 RA cases and 2223 controls (both median age 55, 76% female). Acute sinusitis (OR 1.61, 95% CI 1.05-2.45), chronic sinusitis (OR 2.16, 95% CI 1.39-3.35), and asthma (OR 1.39, 95% CI 1.03-1.87) were associated with increased risk of RA. Acute respiratory tract disease burden during the preindex exposure period was also associated with increased RA risk (OR 1.30 per 10 codes, 95% CI 1.08-1.55). Acute pharyngitis was associated with seronegative (OR 1.68, 95% CI 1.02-2.74) but not seropositive RA; chronic rhinitis/pharyngitis was associated with seropositive (OR 2.46, 95% CI 1.01-5.99) but not seronegative RA. Respiratory tract diseases tended towards higher associations in smokers, especially > 10 pack-years (OR 1.52, 95% CI 1.02-2.27, P = 0.10 for interaction).Conclusion: Acute and chronic sinusitis, pharyngitis, and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence and incidence of multimorbidity (MM) in a population-based cohort of patients with rheumatoid arthritis (RA) compared to subjects without RA.Methods: Between 1999-2013, residents of Olmsted County, Minnesota with incident RA who met the 1987 American College of Rheumatology criteria were compared to age- and sex-matched non-RA subjects from the same population. Twenty-five chronic comorbidities from a combination of the Charlson, Elixhauser, and Rheumatic Disease Comorbidity Indices were included, excluding rheumatic comorbidities. The Aalen-Johansen method was used to estimate the cumulative incidence of MM (MM2+; ≥ 2 chronic comorbidities) or substantial MM (MM5+; ≥ 5), adjusting for the competing risk of death.Results: The study included 597 patients with RA and 594 non-RA subjects (70% female, 90% White, mean age 55.5 yrs). At incidence/index date, the prevalence of MM2+ was higher in RA than non-RA subjects (38% RA vs 32% non-RA, P = 0.02), whereas prevalence of MM5+ was similar (5% RA vs. 4% non-RA, P = 0.68). During follow-up (median 11.6 yrs RA, 11.3 yrs non-RA), more patients with RA developed MM2+ (214 RA vs 188 non-RA; adjusted HR 1.39, 95% CI 1.14-1.69). By 10 years after RA incidence/index, the cumulative incidence of MM2+ was 56.5% among the patients with RA (95% CI 56.5-62.3%) compared with 47.9% among the non-RA (95% CI 42.8-53.7%). Patients with RA showed no evidence of increase in incidence of MM5+ (adjusted HR 1.17, 95% CI 0.93-1.47).Conclusion: Patients with RA have both a higher prevalence of MM at the time of RA incidence as well as increased incidence thereafter. [ABSTRACT FROM AUTHOR]

Objective: Both erectile dysfunction (ED) and rheumatoid arthritis (RA) are associated with increased cardiovascular (CV) risk. It is unknown if these diagnoses are associated or if their combination confers additional CV risk. We aimed to define the incidence of ED in RA, and to determine if ED correlates with increased CV risk in RA.Methods: Medical information concerning RA, ED, and CV diagnoses for men with RA (n = 260) diagnosed in Olmsted County, Minnesota, and age-matched male comparators was extracted from a comprehensive medical record system.Results: ED incidence was similar between the RA cohort and comparators (HR 0.80, 95% CI 0.55-1.16). In men with RA, ED diagnosis was associated with a trend toward an increase in peripheral arterial disease (HR 2.22, 95% CI 0.98-5.03) and a significantly decreased rate of myocardial infarction (HR 0.26, 95% CI 0.07-0.90), heart failure (HR 0.49, 95% CI 0.25-0.94), and death (HR 0.56; 95% CI 0.36-0.87). In men with RA and ED, phosphodiesterase-5 inhibitor use was associated with a decreased risk of death (HR 0.35, 95% CI 0.16-0.79), with a trending decreased risk of some CV diagnoses.Conclusion: Incidence of ED was not statistically increased in RA. Although patients with both RA and ED had a similar overall CV risk to those with RA alone, men with both RA and ED had decreased risk of heart failure, myocardial infarction, and death, as well as an increased risk of peripheral arterial disease. Further studies are needed to clarify these associations and their implications for pathogenesis and therapeutics. [ABSTRACT FROM AUTHOR]

Objective: To assess trends in incidence of cardiovascular disease (CVD) and mortality following incident CVD events in patients with rheumatoid arthritis (RA) onset in 1980-2009 vs non-RA subjects.Methods: We studied Olmsted County, Minnesota residents with incident RA (aged > 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009) and non-RA subjects from the same source population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2016. Incident CVD events included myocardial infarction and stroke. Patients with CVD before RA incidence/index date were excluded. Cox models were used to compare incident CVD events by decade, adjusting for age, sex, and CVD risk factors.Results: The study included 905 patients with RA and 904 non-RA subjects. Cumulative incidence of any CVD event was lower in patients with incident RA in the 2000s vs the 1980s. The HR for any incident CVD in the 2000s vs 1980s was 0.53 (95% CI 0.31-0.93). The strength of association attenuated after adjustment for anti-rheumatic medication use (HR 0.64, 95% CI 0.34-1.22). Patients with RA in the 2000s had no excess in CVD over non-RA subjects (HR 0.71, 95% CI 0.42-1.19). Risk of death after a CVD event was somewhat lower in patients with RA after the 1980s with an HR of 0.54 (95% CI 0.33-0.90) in the 1990s vs 1980s and 0.68 (95% CI 0.33-1.41) in the 2000s vs 1980s.Conclusion: The incidence of major CVD events in RA has declined in recent decades. The gap in CVD occurrence between patients with RA and the general population is closing. Mortality after CVD events in RA may be improving. [ABSTRACT FROM AUTHOR]

We aimed to assess the incidence of dementia over time in patients with incident rheumatoid arthritis (RA) as compared to non-RA referents. This population-based, retrospective cohort study included Olmsted County, Minnesota residents with incident RA by ACR 1987 criteria, diagnosed between 1980 and 2009. We matched non-RA referents 1:1 on age, sex, and calendar year and followed all individuals until 12/31/2019. Incident dementia was defined as two codes for Alzheimer's disease and related dementias (ADRD) at least 30 days apart. Cumulative incidence of ADRD was assessed, adjusting for the competing risk of death. Cox proportional hazards models calculated hazard ratios (HR) with 95% confidence intervals (CI) for incident ADRD by decade. After excluding individuals with prior dementia, we included 897 persons with incident RA (mean age 56 years; 69% female) and 885 referents. The 10-year cumulative incidence of ADRD in individuals diagnosed with RA during the 1980s was 12.7% (95%CI:7.9–15.7%), 1990s was 7.2% (95%CI:3.7–9.4%), and 2000s was 6.2% (95%CI:3.6–7.8%). Individuals with RA diagnosed in 2000s had insignificantly lower cumulative incidence of ADRD than those in the 1980s (HR 0.66; 95%CI:0.38–1.16). The overall HR of ADRD in individuals with RA was 1.37 (vs. referents; 95%CI:1.04–1.81). When subdivided by decade, however, the risk of ADRD in individuals diagnosed with RA was higher than referents in the 1990s (HR 1.72, 95%CI:1.09–2.70) but not 2000s (HR 0.86, 95%CI:0.51–1.45). The risk of dementia in individuals with RA appears to be declining over time, including when compared to general population referents. [ABSTRACT FROM AUTHOR]

• Morbidities are associated with serious infection risk in rheumatoid arthritis. • Bipolar disorder, dementia, and vitamin D deficiency pose the greatest risk. • Highest risk morbidities are associated with a 3–6-fold risk of serious infection. • Serious infection risk increases by 16 % per morbidity. • The risk of many morbidities is not fully accounted for in 2 common risk models. To assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA). This study evaluated SI risk associated with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score. 911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11–16 % per morbidity in the three models. Several morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between novel lifestyle factors on risk of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), define the threshold at which smoking increases RA-ILD risk, and calculate the degree to which known lifestyle and clinical factors predict RA-ILD.Methods: This nested case-control study matched incident RA-ILD cases to RA non-ILD controls on age, sex, RA duration, rheumatoid factor, and time from exposure assessment to RA-ILD. Exposures included education, BMI, smoking, anticyclic citrullinated peptide antibodies, race, joint erosions, rheumatoid nodules, C-reactive protein (CRP), disease activity score, functional status, disease-modifying antirheumatic drug use, and glucocorticoid use. OR for each exposure on risk of RA-ILD were obtained from logistic regression models. Area under the curve (AUC) was calculated based on all lifestyle and clinical exposures.Results: We identified 84 incident RA-ILD cases and 233 matched controls. After adjustment, obesity, high-positive CRP (≥ 10 mg/L), and poor functional status (multidimensional Health Assessment Questionnaire [MDHAQ] ≥ 1) were associated with increased risk of RA-ILD (OR 2.42, 95% CI 1.11-5.24 vs normal BMI; OR 2.61, 95% CI 1.21-5.64 vs CRP < 3 mg/L; OR 3.10, 95% CI 1.32-7.26 vs MDHAQ < 0.2). Smoking 30 pack-years or more was strongly associated with risk of RA-ILD compared to never smokers (OR 6.06, 95% CI 2.72-13.5). Together, lifestyle and clinical risk factors for RA-ILD had an AUC of 0.79 (95% CI 0.73-0.85).Conclusion: Obesity, CRP, functional status, and extensive smoking may be novel risk factors for RA-ILD that may be useful for RA-ILD risk assessment and prevention. The overall ability to predict RA-ILD remains modest. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to evaluate the relationships between multimorbidity and overall fatigue as well as fatigue subdomains in patients with rheumatoid arthritis (RA). Methods: A cross-sectional study of a population-based cohort of patients with RA was performed. Fatigue was assessed using the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Patients' medical records were reviewed for 25 chronic comorbidities prior to the BRAF-MDQ. Linear and logistic regression models were used to estimate the differences in BRAF-MDQ total and subdomain (physical, living, cognitive, and emotional) scores associated with multimorbidity, adjusting for age, sex, disease duration, obesity, smoking, C-reactive protein, and RA autoantibodies. Higher BRAF-MDQ scores indicate greater fatigue severity. Results: The cohort included 192 patients, median age 62 years, and median RA duration 13 years. Multimorbidity was common with 93 (48%) having ≥ 2 comorbidities, and 27 (14%) having ≥ 4 comorbidities. The median BRAF-MDQ total score was 9 (interquartile range 3–18), with higher scores indicating greater fatigue. Patients with ≥ 4 comorbidities had higher total BRAF-MDQ scores (median 16.5, interquartile range: 6.8–24.8) than patients with < 4 comorbidities (7.5, 2.8–16.0; p = 0.014). Each additional comorbidity was associated with a 2.33 (95% confidence interval [CI] 1.10–3.56) unit increase in total BRAF-MDQ score (p < 0.001), and the presence of ≥ 4 comorbidities was associated with a 9.33 (95% CI 3.92–14.7) unit increase in total BRAF-MDQ score. Multimorbidity was significantly associated with all four fatigue subdomains in adjusted models. Conclusions: Multimorbidity is associated with increased fatigue in patients with RA. The findings suggest that interventions targeting multimorbidity could help alleviate treatment-refractory fatigue in patients with RA and other rheumatic diseases. [ABSTRACT FROM AUTHOR]

• Current evidence suggests similar risk of rheumatoid arthritis (RA) statin users vs non-users. • Risk of RA may be decreased with higher statin treatment persistence or intensity. • Studies evaluating cumulative statin exposure on the risk of RA are warranted. Anti-inflammatory and immune-modulating effects of statins suggest that they may play a role in the risk of rheumatoid arthritis (RA). We aimed to perform a systematic review and meta-analysis of studies assessing the risk of RA in statin-users versus non-users. We searched Medline from inception to 01/22/2019 and Embase from 1988 to Week 03 2019 for studies that examined the association between statin use and RA without restrictions on language. We identified 1,161 references; of them 8 studies (5 cohort studies and 3 case-control studies) were included in the systematic review. Four cohort studies comparing statin-users versus non-users were included in the meta-analysis. The pooled risk ratio (RR) was 1.01; 95%CI 0.93–1.10; I 2 = 17%. Case-control studies showed highly heterogeneous results (I 2 = 92%) and were not included in the meta-analysis. One cohort study and one case-control study assessing persistence with or intensity of treatment with statins showed lower risk of RA with higher versus lower treatment persistence or intensity of statin use (pooled RR 0.66; 95%CI 0.5–0.87; I 2 = 83%). The certainty in the evidence was low. In this systematic review and meta-analysis, we observed no difference in risk of RA in statin users vs non-users. Risk of RA may be lower in patients with higher versus lower statin treatment persistence or intensity. Future observational studies with guards against selection bias and confounding are needed to further elucidate the impact of statin use on the risk of RA, considering potential differences by dosage, duration of use, study population and other factors. [ABSTRACT FROM AUTHOR]

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: "T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3" (n = 9) and "T1IFN detectable but IFNβ/α ≤ 1.3" (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: "T1IFN ND," "T1IFN detected and IFNβ/α ≤ 1.3," and "IFNβ/α >1.3." Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNβ/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNβ/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi. [ABSTRACT FROM AUTHOR]

To compare the frequency of and trends in hospitalizations after heart failure (HF) diagnosis in patients with and without rheumatoid arthritis (RA) during 1987–2015. The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age≥18 years, 1987 ACR criteria) and a cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF diagnosis. Hospitalizations at the time of HF diagnosis were excluded. All subjects were followed until death, migration, or 12/31/2015. The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean age at HF diagnosis 78.6 years; 68% female). The hospitalization rate after HF diagnosis was higher in RA vs non-RA (rate ratio [RR] 1.17; 95%CI 1.08-1.26). Hospitalization rates in both groups have been declining since 2005 and the difference between patients with and without RA may be decreasing after 2010. The magnitude of the increase was similar in both sexes and across all ages. Patients with RA were more likely to be hospitalized for non-cardiovascular causes (RR 1.26; 95%CI 1.14-1.39), but not for HF or other cardiovascular causes compared to non-RA patients. The hospitalization rate following HF diagnosis was higher in RA versus non-RA patients regardless of sex and age. Increased hospitalization risk in patients with RA was driven by increased rates of non-cardiovascular hospitalization. [ABSTRACT FROM AUTHOR]

Multiple data sources are preferred in adverse drug event (ADEs) surveillance owing to inadequacies of single source. However, analytic methods to monitor potential ADEs after prolonged drug exposure are still lacking. In this study we propose a method aiming to screen potential ADEs by combining FDA Adverse Event Reporting System (FAERS) and Electronic Medical Record (EMR). The proposed method uses natural language processing (NLP) techniques to extract treatment outcome information captured in unstructured text and adopts case-crossover design in EMR. Performances were evaluated using two ADE knowledge bases: Adverse Drug Reaction Classification System (ADReCS) and SIDER. We tested our method in ADE signal detection of conventional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis patients. Findings showed that recall greatly increased when combining FAERS with EMR compared with FAERS alone and EMR alone, especially for flexible mapping strategy. Precision (FAERS + EMR) in detecting ADEs improved using ADReCS as gold standard compared with SIDER. In addition, signals detected from EMR have considerably overlapped with signals detected from FAERS or ADE knowledge bases, implying the importance of EMR for pharmacovigilance. ADE signals detected from EMR and/or FAERS but not in existing knowledge bases provide hypothesis for future study. [ABSTRACT FROM AUTHOR]

To examine time trends in glucocorticoid (GC) use among patients diagnosed with rheumatoid arthritis (RA) during the biologic era. A population-based inception cohort of RA patients diagnosed during 1999 – 2018 was followed longitudinally through their medical records until death, migration or 12/31/2020. All patients fulfilled 1987 American College of Rheumatology classification criteria for RA. GC start and stop dates were collected along with dosages in prednisone equivalents. The cumulative incidence of GC initiation and discontinuation adjusted for the competing risk of death was estimated. Cox models adjusted for age and sex were used to compare trends between time periods. The study population included 399 patients (71% female) diagnosed in 1999 – 2008 and 430 patients (67% female) diagnosed in 2009 – 2018. GC use was initiated within 6 months of meeting RA criteria in 67% of patients in 1999-2008 and 71% of patients in 2009-2018, corresponding to a 29% increase in hazard for initiation of GC in 2009-2018 (adjusted hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.09-1.53). Among GC users, similar rates of GC discontinuation within 6 months after GC initiation were observed in patients with RA incidence in 1999 – 2008 and 2009 – 2018 (39.1% versus 42.9%, respectively), with no significant association in adjusted Cox models (HR: 1.11; 95% CI: 0.93-1.31). More patients are initiating GCs early in their disease course now compared to previously. The rates of GC discontinuation were similar, despite the availability of biologics. [ABSTRACT FROM AUTHOR]

To assess transition probability between different levels of functional disability (FD) and time spent with FD in patients with versus without rheumatoid arthritis (RA) after RA incidence/index date. This retrospective population-based cohort study included Olmsted County, Minnesota residents (1987 ACR criteria met in 1999–2013) and comparators without RA from the same area with similar age, sex and RA incidence/index date. Activities of Daily Living (ADL) were obtained by self-report questionnaires annually since 1999. FD was defined as having difficulty with ≥1 ADL. Multistate modeling was used to estimate the probability of transitioning between FD states. Five hundred fifty-eight patients with RA and 457 comparators completed ≥2 questionnaires and were included. Patients with RA had increased risk of transitioning from no FD to FD: Hazard Ratio (HR) 2.4; 95%CI:1.9–3.0. Each additional FD at RA onset reduced the probability of returning to no FD by 14%. However, the probability of having ≥1 FD was stable between RA incidence and 10-year follow-up. In the first 15 years of disease, patients with RA spent on average 10.1 years without FD and 3.4 years with ≥1 FD versus 11.6 years and 2.0 years (p <0.001) in comparators. Patients with RA remain functionally disadvantaged compared to individuals without RA. The likelihood of returning to no FD in RA decreases with each additional preexisting FD. However, the probability of FD does not increase within 10 years of RA onset, potentially reflective of the benefits of disease-modifying treatments in RA. [ABSTRACT FROM AUTHOR]

The article compares the clinical presentation, management as well as outcome of heart failure in patients with rheumatoid arthritis (RA) with non-RA subjects. Methodology-wise, the researchers conducted a community-based cohort study. Based on the results, they concluded that the findings emphasize the importance of more vigilant screening in patients with RA for early signs of the disease.

The article discusses a study on the mortality trends among rheumatoid arthritis (RA) patients compared with those in the general population. The mortality rates for female and male RA patients were 2.4 and 2.5 per 100 person-years, respectively, between 1965 and 2005. It found that the difference between the observed and expected mortality rates increased in more recent years, which resulted in a wider mortality gap. The findings indicate that RA patients have not experienced improvements in survival over the period.

The article presents a study which examined the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA). Results showed that rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events. According to the authors, the findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA.

To identify associations between immunostimulated cytokine production and disease characteristics, peripheral blood lymphocytes were collected from 155 adult patients with rheumatoid arthritis (RA) before and after a 5-year interval. The lymphocytes were activated in vitro with T-cell stimulants, cytosine-phosphate-guanine (CpG) oligonucleotide, and medium alone (negative control). Expression of 17 cytokines was evaluated with immunoassays, and factor analysis was used to reduce data complexity and identify cytokine combinations indicative of cell types preferentially activated by each immunostimulant. The findings showed that the highest numbers of correlations were between cytokine levels and rheumatoid factor (RF) positivity and between cytokine levels and disease duration. Scores for cytokines driven by CpG and medium alone were negatively associated with RF positivity and disease duration at baseline but positively associated with both at 5 years. Our findings suggest that RF expression sustained over time increases activation of B cells and monocytes without requirements for T-cell functions. • Cytokines were associated with rheumatoid factor and rheumatoid arthritis duration. • Cytokine profiles switched from T-cell to B-cell cytokines over 5 years. • Cytosine-phosphate-guanine response profiles suggested an innate immune response. • Sustained rheumatoid factor expression likely activates B cells and monocytes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the risk of subsequent development of chronic obstructive pulmonary disease (COPD) in patients with rheumatoid arthritis (RA).Methods: We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence interval (CI), comparing risk of incident COPD in patients with RA versus non-RA participants. Pooled risk ratio and 95% CI were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird.Results: Four retrospective cohort studies with 32,675 patients with RA and 122,204 controls were included in the data analysis. The pooled risk ratio of incident COPD in patients with RA versus control was 1.99 (95% CI, 1.61-2.45). The statistical heterogeneity was high with an I2 of 81%.Conclusion: Our study demonstrated a statistically significant increased risk of subsequent development of COPD among patients with RA. [ABSTRACT FROM AUTHOR]