Virtual Scribes and Physician Time Spent on Electronic Health Records.

Importance: Time on the electronic health record (EHR) is associated with burnout among physicians. Newer virtual scribe models, which enable support from either a real-time or asynchronous scribe, have the potential to reduce the burden of the EHR and EHR-related documentation. Objective: To characterize the association of use of virtual scribes with changes in physicians' EHR time and note and order composition and to identify the physician, scribe, and scribe response factors associated with changes in EHR time upon virtual scribe use. Design, Setting, and Participants: Retrospective, pre-post quality improvement study of 144 physicians across specialties who had used a scribe for at least 3 months from January 2020 to September 2022, were affiliated with Brigham and Women's Hospital and Massachusetts General Hospital, and cared for patients in the outpatient setting. Data were analyzed from November 2022 to January 2024. Exposure: Use of either a real-time or asynchronous virtual scribe. Main Outcomes: Total EHR time, time on notes, and pajama time (5:30 pm to 7:00 am on weekdays and nonscheduled weekends and holidays), all per appointment; proportion of the note written by the physician and team contribution to orders. Results: The main study sample included 144 unique physicians who had used a virtual scribe for at least 3 months in 152 unique scribe participation episodes (134 [88.2%] had used an asynchronous scribe service). Nearly two-thirds of the physicians (91 physicians [63.2%]) were female and more than half (86 physicians [59.7%]) were in primary care specialties. Use of a virtual scribe was associated with significant decreases in total EHR time per appointment (mean [SD] of 5.6 [16.4] minutes; P < .001) in the 3 months after vs the 3 months prior to scribe use. Scribe use was also associated with significant decreases in note time per appointment and pajama time per appointment (mean [SD] of 1.3 [3.3] minutes; P < .001 and 1.1 [4.0] minutes; P = .004). In a multivariable linear regression model, the following factors were associated with significant decreases in total EHR time per appointment with a scribe use at 3 months: practicing in a medical specialty (-7.8; 95% CI, -13.4 to -2.2 minutes), greater baseline EHR time per appointment (-0.3; 95% CI, -0.4 to -0.2 minutes per additional minute of baseline EHR time), and decrease in the percentage of the note contributed by the physician (-9.1; 95% CI, -17.3 to -0.8 minutes for every percentage point decrease). Conclusions and Relevance: In 2 academic medical centers, use of virtual scribes was associated with significant decreases in total EHR time, time spent on notes, and pajama time, all per appointment. Virtual scribes may be particularly effective among medical specialists and those physicians with greater baseline EHR time.

The Safety of Outpatient Health Care : Review of Electronic Health Records.

BACKGROUND: Despite considerable emphasis on delivering safe care, substantial patient harm occurs. Although most care occurs in the outpatient setting, knowledge of outpatient adverse events (AEs) remains limited. OBJECTIVE: To measure AEs in the outpatient setting. DESIGN: Retrospective review of the electronic health record (EHR). SETTING: 11 outpatient sites in Massachusetts in 2018. PATIENTS: 3103 patients who received outpatient care. MEASUREMENTS: Using a trigger method, nurse reviewers identified possible AEs and physicians adjudicated them, ranked severity, and assessed preventability. Generalized estimating equations were used to assess the association of having at least 1 AE with age, sex, race, and primary insurance. Variation in AE rates was analyzed across sites. RESULTS: The 3103 patients (mean age, 52 years) were more often female (59.8%), White (75.1%), English speakers (90.8%), and privately insured (70.4%) and had a mean of 4 outpatient encounters in 2018. Overall, 7.0% (95% CI, 4.6% to 9.3%) of patients had at least 1 AE (8.6 events per 100 patients annually). Adverse drug events were the most common AE (63.8%), followed by health care-associated infections (14.8%) and surgical or procedural events (14.2%). Severity was serious in 17.4% of AEs, life-threatening in 2.1%, and never fatal. Overall, 23.2% of AEs were preventable. Having at least 1 AE was less often associated with ages 18 to 44 years than with ages 65 to 84 years (standardized risk difference, -0.05 [CI, -0.09 to -0.02]) and more often associated with Black race than with Asian race (standardized risk difference, 0.09 [CI, 0.01 to 0.17]). Across study sites, 1.8% to 23.6% of patients had at least 1 AE and clinical category of AEs varied substantially. LIMITATION: Retrospective EHR review may miss AEs. CONCLUSION: Outpatient harm was relatively common and often serious. Adverse drug events were most frequent. Rates were higher among older adults. Interventions to curtail outpatient harm are urgently needed. PRIMARY FUNDING SOURCE: Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.

Understanding Differences in Patient Descriptions of Rheumatoid Arthritis Flares Using OMERACT Core Domains.

OBJECTIVE: Recently, there has been consensus on domains that constitute flares in rheumatoid arthritis (RA); however, variations in patients' flare descriptions continue to be observed. This study evaluates how demographic and clinical characteristics influence these differences. METHODS: Participants enrolled in a prospective RA registry completed a qualitative survey that included the open-ended question "What does a flare mean to you?" Responses were categorized into Outcome Measures in Rheumatology (OMERACT) core and research domains. Univariate analyses evaluated demographic and clinical characteristics. Regression analyses determined independent variables associated with flare description variations. RESULTS: Among 645 participants, the median Disease Activity Score in 28 joints (DAS28) with C-reactive protein was 2.1 (IQR 1.6-2.9); 58% of the participants reported at least 1 flare in the past 6 months. Participants reported a median of 3 (IQR 2-5) OMERACT domains when describing flares. Fatigue was more commonly noted among females (odds ratio [OR] 6.12; P < 0.001). Older participants were less likely to report emotional distress (OR 0.97; P = 0.03), swollen joints (OR 0.99; P = 0.04), physical function decrease (OR 0.98; P = 0.02), and a general increase in RA symptoms (OR 0.98; P = 0.005). Participants with a higher DAS28 score were less likely to report symptoms of stiffness (OR 0.70; P = 0.009), and those who experienced a flare within the last 6 months were more likely to describe flares as pain (OR 2.53; P < 0.001) and fatigue (OR 2.00; P = 0.007). CONCLUSION: Variations in patients' flare descriptions can be driven by a patient's disease activity, the experience of a recent flare, as well as different demographic characteristics, such as age and gender. Understanding the interplay of these characteristics can guide a physician's approach to the management of patients' RA flares.

The Safety of Inpatient Health Care.

BACKGROUND: Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted. METHODS: We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events. RESULTS: In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%). CONCLUSIONS: Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).

Serum proteomic profiling of rheumatoid arthritis-interstitial lung disease with a comparison to idiopathic pulmonary fibrosis.

Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets.

Screening for preclinical parenchymal lung disease in rheumatoid arthritis.

OBJECTIVES: Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD). METHODS: RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities. RESULTS: Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures. CONCLUSION: We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.

An analysis of the structure and content of dashboards used to monitor patient safety in the inpatient setting.

The objective of this study is to review and compare patient safety dashboards used by hospitals and identify similarities and differences in their design, format, and scope. We reviewed design features of electronic copies of patient safety dashboards from a representative sample of 10 hospitals. The results show great heterogeneity in the format, presentation, and scope of patient safety dashboards. Hospitals varied in their use of performance indicators (targets, trends, and benchmarks), style of color coding, and timeframe for the displayed metrics. The average number of metrics per dashboard display was 28, with a wide range from 7 to 84. Given the large variation in dashboard design, there is a need for future work to assess which approaches are associated with the best outcomes, and how specific elements contribute to usability, to help customize dashboards to meet the needs of different clinical, and operational stakeholders.

Divergence of Cardiovascular Biomarkers of Lipids and Subclinical Myocardial Injury Among Rheumatoid Arthritis Patients With Increased Inflammation.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury. METHODS: A total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high-sensitivity C-reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin-6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro-brain natriuretic peptide) were measured. RESULTS: Among the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A-I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs-cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs-cTnT levels remained stable despite a reduction in inflammation over follow-up. In both cohorts, hs-cTnT levels were associated with the overall estimated risk of CVD. CONCLUSION: Among RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs-cTnT for CVD risk stratification in RA.

Lifestyle and Clinical Risk Factors for Incident Rheumatoid Arthritis-associated Interstitial Lung Disease.

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.

Rheumatoid arthritis-related lung disease detected on clinical chest computed tomography imaging: Prevalence, risk factors, and impact on mortality.

OBJECTIVE: We aimed to determine the real-world prevalence and investigate risk factors for rheumatoid arthritis (RA)-related lung disease on chest computed tomography (CT) imaging. We also investigated the impact of RA-related lung disease on mortality. METHODS: We studied chest CT imaging abnormalities among RA patients. We determined the presence and type of abnormalities using the chest CT imaging radiologic report. RA-related lung disease was defined as interstitial lung disease (ILD), bronchiectasis, or pleural disease. We examined whether demographics and RA characteristics were associated with RA-related lung disease using logistic regression. RA-related lung disease and mortality was described using survival curves and Cox regression. RESULTS: We analyzed 190 patients who had chest CT imaging performed for clinical indications. Mean age was 64.2 years (SD 11.8), 80.0% were female, and 75.3% were seropositive. RA-related lung disease was detected in 54 patients (28.4%); 30 (15.8%) had ILD, 27 (14.2%) had bronchiectasis, and 18 (9.5%) had pleural disease. RA-related lung disease was reported in both seropositive and seronegative RA (28.7% vs. 27.7%, p = 1.00). Male sex (OR 2.62, 95%CI 1.17-5.88) and current methotrexate use (OR 2.73, 95%CI 1.27-5.61 vs. not current) were associated with RA-related lung disease. Twenty-four (44.4%) patients with RA-related lung disease died during mean 7.0 years of follow-up. RA-related lung disease had HR of 5.35 (95%CI 0.72-39.9) for mortality compared to normal chest CT. CONCLUSIONS: In this real-world study, RA-related lung disease was commonly detected on chest CT imaging regardless of RA serostatus. RA-related lung disease had high mortality, emphasizing the importance in close monitoring of these patients.

Correction to: Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry.

The publisher regrets that the two sections under the Results omitted inadvertently on the original published version of the above article.

Correlates of Successful Rheumatoid Arthritis Flare Management: Clinician-driven Treatment, Home-based Strategies, and Medication Change.

OBJECTIVE: Describe strategies used to manage rheumatoid arthritis (RA) flares that contribute to a successful postflare outcome. METHODS: Data were collected from the BRASS registry, including clinical and patient-reported outcomes, and a survey with a Likert scale assessing postflare symptoms (better, unchanged, or worse). A logistic regression analysis adjusting for age, sex, flare number in the past 6 months, flare pain severity, home management, clinical consultation, and medication change was performed to evaluate factors influencing flare outcome. RESULTS: Of 503 participants, 185 reported at least 1 flare that had resolved in the past 6 months, with median (interquartile range) 28-joint count Disease Activity Score based on C-reactive protein 3 score 2.1 (1.7-2.8). Compared with RA symptoms before the flare, 22 (12%) patients felt worse, 125 (68%) were unchanged, and 38 (20%) felt better. To manage flares, 72% of patients used home-based remedies, 23% sought clinical consultation, and 56% made medication change. Of 103 patients who changed medication, 70% did so without seeking clinical advice. Making a medication change (OR 3.48, 95% CI 1.68-7.21) and having lower flare pain (OR 0.83, 95% CI 0.71-0.97) were associated with better flare outcome. CONCLUSION: Flares occur frequently even in patients with low disease activity. Independent of home-based or clinically guided care, making a medication change and having less severe pain during a flare were associated with better flare outcomes. Of interest, the decision to change medications was frequently made without clinical advice. Future studies might address how best to intervene when patients experience flares and whether patient-initiated medication changes have adverse outcomes.

The Impact of Exercise, Lifestyle, and Clinical Factors on Perceived Cognitive Function in Patients with Rheumatoid Arthritis: Results from a Prospective Cohort Study.

OBJECTIVE: Lifestyle factors, such as inactivity and obesity, contribute to cognitive decline in the general population, but little is known about how these factors may affect individuals with a chronic inflammatory condition such as rheumatoid arthritis (RA). We studied the clinical and functional risk factors related to a worsening of perceived cognitive function in patients with RA. METHODS: We collected clinical and functional questionnaire data over 10 years in a prospective RA cohort including yearly self-reported memory, concentration, and word-finding difficulties graded from "never" to "often." Generalized estimating equation models examined the role of exercise (defined as those meeting the Department of Health and Human Services physical activity guidelines of 75 minutes of vigorous or 150 minutes of moderate aerobic activity per week), body mass index (BMI), sleep, depression (Mental Health Index-Depression), Disease Activity Score (DAS)28-c-reactive protein (CRP)3 score, disease-modifying antirheumatic drug, and corticosteroid use from the previous year as predictors of cognitive complaints that progressed to "often" compared with the previous year (the first year (T i ) progressed to "often" 1 year later (T i+1)). RESULTS: Of 1219 RA subjects, 127 (10.4%) described either poor memory, concentration, or word-finding difficulties as affecting them "often" at study entry. RA patients (n = 1092, mean age = 56.5 years, 82% female, 58% college educated) were less likely to report word-finding difficulties, poor memory, and concentration as "often" if they were physically active (p = 0.0001, P = 0.01, P < 0.0001, respectively). Female RA patients developed more concentration complaints compared with males (P = 0.03); patients taking an anti-tumor necrosis factor therapy were less likely to complain of poor memory (P = 0.01). Sleep, BMI, fatigue, depression, DAS28-CRP3, methotrexate, and corticosteroid use were not independently associated with a worsening of any cognitive complaints. CONCLUSION: RA patients who are physically active are less likely to report cognitive difficulties. Our study suggests potential modifiable risk factors for the prevention of cognitive dysfunction in RA.

Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry.

INTRODUCTION: We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs). METHODS: We studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95% CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics. RESULTS: Among 1272 analyzed subjects, mean age was 56.3 years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared with seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95% CI 1.30-4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95% CI 1.26-4.87), 3.12 (95% CI 1.28-7.61), and 2.30 (95% CI 1.09-4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality OR 1.99, 95% CI 1.21-3.27 for RF+ vs. RF-; OR 1.67, 95% CI 1.03-2.69 for CCP+ vs. CCP-) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend < 0.05). CONCLUSIONS: Seropositive RA patients had two-fold increased risk for abnormalities on PFTs performed for clinical indications compared with seronegative RA. Patients with seropositive RA, particularly those with high-titer RF positivity, may be more likely to have obstructive and restrictive abnormalities, independent of smoking.Key points• Due to the known excess pulmonary morbidity/mortality in RA, we studied the relationship of rheumatoid arthritis (RA)-related autoantibodies with pulmonary function test (PFT) abnormalities using a large RA registry.• We evaluated whether presence and levels of cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were associated with restriction, obstruction, and diffusion abnormalities on PFTs among 1272 subjects with RA.• Seropositivity was associated with two-fold increased risk for any PFT abnormality, independent of confounders including smoking. Higher titers of RF conferred greatest risk for all PFT outcomes: obstruction, restriction, and diffusion abnormality.• These results provide evidence that patients with RA should be closely monitored for pulmonary involvement, particularly those with high-titer RF seropositivity.

The longitudinal effect of biologic use on patient outcomes (disease activity, function, and disease severity) within a rheumatoid arthritis registry.

INTRODUCTION: Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. METHOD: Longitudinal data were examined from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry. Linear regression modeled the effect of biologic exposure on changes in disease activity (Disease Activity Score-28 with C-reactive protein [DAS28-CRP]), functional status (modified Health Assessment Questionnaire [mHAQ]), and RA severity (Routine Assessment of Patient Index Data [RAPID3]). Biologic exposure was the ratio of time on a biologic relative to time participating in the BRASS cohort. RESULTS: The analysis included 1395 RA patients, 82.3% female, with 6783 unique study visits from 2003 to 2015. At the patient's first visit, mean (SD) age was 56.3 (14.2) years and mean (SD) duration of RA was 12.7 (11.9) years. Average follow-up duration was 5.59 years (range, 1-13). Over time, DAS28-CRP, mHAQ, and RAPID3 scores decreased as the biologic exposure ratio increased. In repeated measures regression models, increased biologic exposure was significantly associated with decreased DAS28-CRP score (ß = - 0.647; P < 0.001), decreased mHAQ score (ß = - 0.096; P < 0.001), and decreased RAPID3 score (ß = - 0.724; P < 0.001) during follow-up. Methotrexate use at baseline predicted decreased DAS28-CRP, mHAQ, and RAPID3 scores during follow-up. Biologic use at baseline predicted increased DAS28-CRP or mHAQ during follow-up. CONCLUSIONS: Increased biologic exposure is associated with decreased disease activity, function impairment, and RA severity. Future studies should examine whether earlier initiation of biologics improves patient outcomes in RA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01793103 Key Points • Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. • In this analysis of longitudinal annual population samples of 1395 RA patients in the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry, disease activity, function, and severity scores improved as time on biologic therapy increased. • In repeated measures regression models, time on biologic therapy was a significant predictor of improved outcomes for disease activity, function, and RA severity. • Further studies should examine whether earlier initiation of biologics limits the long-term effect of inflammation on RA outcomes.

Interference of tumor necrosis factor inhibitor treatments on soluble tumor necrosis factor receptor 2 levels in rheumatoid arthritis.

OBJECTIVE: Soluble Tumor Necrosis Factor Receptor II (sTNFR2) is used as a biomarker to study cardiovascular disease (CVD) in diverse populations. TNF inhibitors (TNFi's) are a common treatment for inflammatory conditions. The objective of this study was to examine whether TNFi use impacts measured sTNFR2 levels. METHODS: We studied blood samples from a cohort of RA patients with clinical data and high sensitivity-C-reactive protein (hsCRP) measurements. To assess for interference, we tested the entire cohort for the expected positive correlation between sTNFR2 and TNFi using Pearson correlations. We then performed Pearson correlations between sTNFR2 and TNFi and sequentially removed subjects on adalimumab, etanercept, and infliximab; if interference was occurring, no correlation would be observed between hsCRP and sTNFR2, and correlation would be restored by removing subjects on the treatment causing the interference. RESULTS: We studied 190 subjects, 84.2% female, 73.4% anti-CCP positive. All subjects with sTNFR2 level exceeding measurable level were on etanercept. The expected positive correlation between hsCRP and sTNFR2 was not observed when assessing the entire cohort, r = 0.05, p = 0.51. However, the expected correlation was restored only after excluding subjects on etanercept, r = 0.46, p < 0.0001, and not adalimumab or infliximab. ELISA for sTNFR2 was performed using etanercept only and demonstrated direct binding to sTNFR2. CONCLUSIONS: Our data identified interference between etanercept and the TNFR2 assay. Of the TNFi's, only etanercept has a TNF-binding domain modeled after TNFR2. These data should be considered when designing studies using sTNFR2 in populations where etanercept is a treatment option.

Association of Changes in Anticitrullinated Protein Antibody Levels With Resource Use and Disease Activity Measures in Rheumatoid Arthritis Patients a US Observational Cohort.

PURPOSE: Anticitrullinated protein antibody (ACPA) concentration, beyond ACPA positivity, is indicative of more aggressive radiographic progression in patients with rheumatoid arthritis (RA). However, there is limited information on the association of changes in ACPA with resource use measures and/or disease activity measures. We evaluate associations between changes in levels of ACPA and outcomes, including durable medical equipment (DME) use, hospitalizations, and disease activity, in patients with established RA. METHODS: Patients from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study who had ACPA measurements at baseline and month 12 were included. Changes in ACPA levels from baseline to month 12 were categorized as a decrease (<-10%), no change (-10% to +10%), or increase (>+10%). DME use and hospitalizations were assessed twice yearly using patient questionnaires; disease activity was assessed annually. Binary multivariate logistic regression was used to analyze the association between changes in ACPA levels and DME use and hospitalizations; linear regression was used to assess the association with disease activity. FINDINGS: Of 840 patients included in the analysis, 291 (34.6%), 266 (31.7%), and 283 (33.7%) had a decrease, no change, or increase in ACPA levels, respectively. A decrease in ACPA levels was associated with a reduction in DME use (adjusted odds ratio [aOR] = 0.64; 95% CI, 0.44-0.93; P = 0.02) and hospitalizations (aOR = 0.62; 95% CI, 0.41-0.95; P = 0.03) versus no change or increase. Adjusted mean changes in disease activity score in 28 joints (C-reactive protein), total and swollen joint counts, and pain scores were significantly greater in patients with decreased ACPA levels versus those with no change or increase (P < 0.05). IMPLICATIONS: Among patients with RA, reductions in ACPA levels of >10% were associated with reductions in DME use, hospitalizations, and disease activity. ClinicalTrials.gov identifier: NCT01793103.

Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Prospective Cohort Study.

OBJECTIVE: To evaluate rheumatoid arthritis (RA) disease activity and risk of RA-associated interstitial lung disease (RA-ILD). METHODS: We investigated disease activity and risk of RA-ILD using the Brigham RA Sequential Study (BRASS, 2003-2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA-ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA-ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD, using annually updated DAS28 data, with adjustment for known RA-ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules. RESULTS: Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA-ILD during a mean ± SD follow-up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28-3.82) for RA-ILD compared to the remission/low disease activity group. Risk of RA-ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61-3.28) for low disease activity, 2.08 (95% CI 1.06-4.05) for moderate disease activity, and 3.48 (95% CI 1.64-7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA-ILD increased by 35% (95% CI 14-60%). Results were similar in analyses that included follow-up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules. CONCLUSION: Active articular RA was associated with an increased risk of developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.

Incidence and predictors of dyspnea on exertion in a prospective cohort of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the incidence and predictors of dyspnea on exertion among subjects with rheumatoid arthritis (RA). METHODS: We investigated dyspnea on exertion using a prospective cohort, the Brigham RA Sequential Study (BRASS). Clinically significant dyspnea on exertion was defined as a score of ≥3 (unable to ambulate without breathlessness or worse) on the validated Medical Research Council (MRC) scale (range 0-5). We analyzed subjects with MRC score <3 at BRASS baseline and ≥1 year of follow-up. The MRC scale was administered annually. We determined the incidence rate (IR) of dyspnea on exertion. We used Cox regression to estimate the HR for dyspnea on exertion occurring one year after potential predictors were assessed. RESULTS: We analyzed 829 subjects with RA and no clinically significant dyspnea on exertion during mean follow-up of 3.0 years (SD 1.9). At baseline, mean age was 55.7 years (SD 13.6), 82.4% were female, and median RA duration was 8 years. During follow-up, 112 subjects (13.5%) developed incident dyspnea on exertion during 2,476 person-years of follow-up (IR 45.2 per 1000 person-years). Independent predictors of incident dyspnea on exertion were: older age (HR 1.03 per year, 95%CI 1.01-1.04), female sex (HR 2.22, 95%CI 1.14-4.29), mild dyspnea (HR 2.62, 95%CI 1.60-4.28), and worsened MDHAQ (HR 2.36 per unit, 95%CI 1.54-3.60). Methotrexate use, RA disease activity, and seropositivity were not associated with incident dyspnea on exertion. CONCLUSION: Dyspnea on exertion occurred commonly in patients with RA. Older women with impaired physical function were especially vulnerable to developing dyspnea on exertion.