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Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.

ObjectiveRecently, 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.MethodsParticipants 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.ResultsAmong 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).ConclusionVariations 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.

Background. Although physical therapy is a proven and recommended intervention for managing rheumatoid arthritis (RA), few studies have explored correlates of physical therapy service use among people with RA. Objective. The purposes of this study were: (1) to describe physical therapy use among people with RA and (2) to identify biopsychosocial factors associated with physical therapy use. It was expected that use of physical therapy services would be lower than previously reported, considering recent medical advancements, and that including contextual factors may lead to identification of new factors associated with physical therapy use. Design. This was a cohort study. Methods. Of 1,032 patients prospectively recruited from a large hospital registry, 772 completed baseline and laboratory assessments, received a physical examination, and completed a 1-year follow-up survey regarding physical therapy service use. Measures included: demographics (ie, age, sex, marital status, race, employment, disability status, insurance, income, comorbidities, and education), disease duration, RA medications, serf-efficacy (assessed with the Arthritis Serf-Efficacy Scale), social support (assessed with the Berkman-Syme Social Network Index), function (assessed with the Multi-Dimensional Health Assessment Questionnaire), and disease activity (assessed with the Rheumatoid Arthritis Disease Activity Index). Self-reported use of physical therapy (yes/no) was assessed at the 1-year follow-up. A staged regression approach, based on a theoretical model, was used to select and enter variables into the regression to develop a parsimonious set of predictors. Results. The patients were well educated and had modestly high incomes, and most had health insurance. Approximately 15.3% of the patients used physical therapy services during the designated follow-up period. Using multivariable modeling, the most significant predictors of physical therapy service use were moderate to high disease activity (odds ratio [OR] = 1.4, 95% confidence interval [CI] = 1.1-1.8), less than a college education (OR=0.5, 95% CI=0.2-0.8), greater social networks (OR=2.1, 95% CI=1.3-3.5), and being on disability (OR=2.4, 95% CI=1.5-4.6). Limitations. The limitations of this study were use of a convenience sample and the potential for misclassification of physical therapy service use. Conclusions. Patients with less than college education were less likely to receive physical therapy services, and those with more active disease, those who were on disability, and those who had greater social networks were more likely to receive physical therapy services., Rheumatoid arthritis (RA), a systemic autoimmune inflammaory disease, affects 1.3 million adults in the United States annually, as reported in 2003, (1) and results in persistent inflammation of synovial tissue. [...]

A treat‐to‐target (TTT) approach improves outcomes in rheumatoid arthritis (RA). In prior work, we found that a learning collaborative (LC) program improved implementation of TTT. We conducted a shorter virtual LC to assess the feasibility and effectiveness of this model for quality improvement and to assess TTT during virtual visits. We tested a 6‐month virtual LC in ambulatory care. The LC was conducted during the 2020–2021 COVID‐19 pandemic when many patient visits were conducted virtually. All LC meetings used videoconferencing and a website to share data. The LC comprised a 6‐hour kickoff session and 6 monthly webinars. The LC discussed TTT in RA, its rationale, and rapid cycle improvement as a method for implementing TTT. Practices provided de‐identified patient visit data. Monthly webinars reinforced topics and demonstrated data on TTT adherence. This was measured as the percentage of TTT processes completed. We compared TTT adherence between in‐person visits versus virtual visits. Eighteen sites participated in the LC, representing 45 rheumatology clinicians. Sites inputted data on 1,826 patient visits, 78% of which were conducted in‐person and 22% of which were held in a virtual setting. Adherence with TTT improved from a mean of 51% at baseline to 84% at month 6 (Pfor trend < 0.001). Each aspect of TTT also improved. Adherence with TTT during virtual visits was lower (65%) than during in‐person visits (79%) (P< 0.0001). Implementation of TTT for RA can be improved through a relatively low‐cost virtual LC. This improvement in TTT implementation was observed despite the COVID‐19 pandemic, but we did observe differences in TTT adherence between in‐person visits and virtual visits.

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.

Patients with rheumatoid arthritis (RA) experience inflamed and damaged joints. RA is an autoimmune disease where proteins called autoantibodies in the blood of patients with RA target the patient’s own joint tissue and organs by mistake. This causes inflammation. Patients with certain autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), may experience worse symptoms. There are certain genetic risk factors that may mean a person is more likely to develop RA. One example of a genetic risk factor is having the shared epitope (SE).

Objective.To investigate demographic, lifestyle, and serologic risk factors for isolated rheumatoid arthritis (RA)–associated bronchiectasis (RA-BR) that is not a result of interstitial lung disease (ILD).Methods.We performed a case-control study using patients with RA from the Mass General Brigham Biobank. We reviewed the records of all patients with RA meeting the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria with computed tomography (CT) chest imaging to identify RA-BR cases and controls with RA and RA-related lung disease. For each patient, the CT chest imaging that was performed closest to enrollment was independently reviewed by 2 radiologists for the presence of RA-related lung diseases. Cases had clinical and radiologic evidence of RA-BR without interstitial lung abnormalities on imaging. Controls had RA and no evidence of bronchiectasis or ILD. We examined the associations between demographic, lifestyle, and serologic factors with RA-BR using multivariable logistic regression.Results.We identified 57 cases of isolated RA-BR and 360 RA controls without RA-related lung disease. In multivariable models, RA-BR was associated with older age at RA onset (OR 1.37 per 10 years, 95% CI 1.02–1.82), lower BMI at RA diagnosis (OR 0.94 per kg/m2, 95% CI 0.89–0.99), seropositive RA (OR 3.96, 95% CI 1.84–8.53), positive rheumatoid factor (OR 4.40, 95% CI 2.14–9.07), and positive anticyclic citrullinated peptide (OR 3.47, 95% CI 1.65–7.31). Higher titers of RA-related autoantibodies were associated with higher odds of RA-BR.Conclusion.Seropositivity, older age at RA diagnosis, and lower BMI at RA onset were associated with isolated bronchiectasis in RA that was not a result of ILD. These findings expand the list of potential risk factors for RA-BR and suggest a pathogenic link between airway inflammation and RA-related autoantibodies.

Background: Cardiac involvement is common in acute Lyme disease, and case reports suggest that cardiac abnormalities might also occur years after the primary infection. Objective: To determine the prevalence of cardiac abnormalities in persons with previously treated Lyme disease. Design: Population-based, retrospective cohort study with controls. Setting: Nantucket Island, Massachusetts. Participants: From among 3703 adult respondents to a total-population (n = 6046) mail survey, 336 (176 case-patients and 160 controls) were randomly selected for clinical evaluation. Measurements: Current cardiac symptoms and major or minor abnormal electrocardiographic features, including heart rate; rhythm; axis; PR, QRS, and QT intervals; QRS structure; atrioventricular blocks; and ST-segment and T-wave changes. Results: Persons with Lyme disease (case-patients, n = 176) (mean duration from disease onset to study evaluation, 5.2 years) and persons without evidence of previous Lyme disease (controls, n = 160) did not differ significantly in their patterns of current cardiac symptoms and electrocardiographic findings, including heart rate (P [is greater than] 0.2), PR interval (P = 0.15), QRS interval (P [is greater than] 0.2), QT interval (P [is greater than] 0.2), axis (P [is greater than] 0.2), presence of arrhythmias (P [is greater than] 0.2), firstdegree heart block (P = 0.12), bundle-branch block (P [is greater than] 0.2), and ST-segment abnormalities (P [is greater than] 0.2). In multivariate analyses that adjusted for age, sex, and previous heart disease, a history of previously treated Lyme disease was not associated with either major (odds ratio, 0.78; P [is greater than] 0.2) or minor (odds ratio, 1.09; P [is greater than] 0.2) electrocardiographic abnormalities. Conclusion: Persons with a history of previously treated Lyme disease do not have a higher prevalence of cardiac abnormalities than persons without a history of Lyme disease., Patients with a history of treated Lyme disease seem no more likely to develop heart abnormalities than patients with no history of Lyme disease. Lyme disease is a bacterial infection carried by ticks. Researchers evaluated heart symptoms and ECG findings of 176 patients treated for Lyme disease and 160 healthy individuals. There were no significant differences in ECG findings or heart symptoms between both groups.

To increase the utility of administrative databases, it has been recommended that they include disease-specific, patient-centered outcome measures. This paper reviews practical and theoretical considerations and the critical evidence to support this recommendation. The strengths and weaknesses of the recommended approach are illustrated by examples of disease-specific measures for arthritis and musculoskeletal diseases. Current experience suggests that routine capture of these measures in administrative databases has formidable practical problems and would be unlikely to affect patient care. They could be used as gross indicators of a population's experience but would be insensitive to clinically meaningful improvement on the level of the individual patient. By themselves' these measures are unlikely to identify actionable strategies to improve outcomes, but they could improve efficiency. Overall, implementing this type of disease management improvement strategy would have little value in direct patient care and would be costly., It is unlikely that the addition of disease-specific information to electronic databases would be a practical, valuable, or cost-effective way to guide individual patient care. Complications associated with using database-derived information for analyses on patients with arthritis are highlighted. The patient's co-existing conditions, age, or treatment expectations can complicate evaluations for one specific disease. Information on specific diseases may be valuable, however, when following general trends for that disease.

Idiopathic multicentric Castleman disease (iMCD) is a poorly understood hematologic disorder involving cytokine-induced polyclonal lymphoproliferation, systemic inflammation, and potentially fatal multiorgan failure. Although the etiology of iMCD is unknown, interleukin-6 (IL-6) is an established disease driver in approximately one-third of patients. Anti–IL-6 therapy, siltuximab, is the only US Food and Drug Administration–approved treatment. Few options exist for siltuximab nonresponders, and no validated tests are available to predict likelihood of response. We procured and analyzed the largest-to-date cohort of iMCD samples, which enabled classification of iMCD into disease categories, discovery of siltuximab response biomarkers, and identification of therapeutic targets for siltuximab nonresponders. Proteomic quantification of 1178 analytes was performed on serum of 88 iMCD patients, 60 patients with clinico-pathologically overlapping diseases (human herpesvirus-8–associated MCD, N = 20; Hodgkin lymphoma, N = 20; rheumatoid arthritis, N = 20), and 42 healthy controls. Unsupervised clustering revealed iMCD patients have heterogeneous serum proteomes that did not cluster with clinico-pathologically overlapping diseases. Clustering of iMCD patients identified a novel subgroup with superior response to siltuximab, which was validated using a 7-analyte panel (apolipoprotein E, amphiregulin, serum amyloid P-component, inactivated complement C3b, immunoglobulin E, IL-6, erythropoietin) in an independent cohort. Enrichment analyses and immunohistochemistry identified Janus kinase (JAK)/signal transducer and activator of transcription 3 signaling as a candidate therapeutic target that could potentially be targeted with JAK inhibitors in siltuximab nonresponders. Our discoveries demonstrate the potential for accelerating discoveries for rare diseases through multistakeholder collaboration.

* Objective: To ascertain the prevalence of and risk factors for long-term sequelae from acute Lyme disease. * Design: Population-based, retrospective cohort study. * Setting: A coastal region endemic for Lyme disease. * Participants: Patients with a history of Lyme disease who were previously treated with antibiotics were compared with randomly selected controls. * Measurements: A standardized physical examination, health status measure (Short Form 36), psychometric test battery, and serologic analysis. * Results: Compared with the control group (n = 43), the Lyme group (n = 38; mean duration from disease onset to study evaluation, 6.2 years) had more arthralgias (61% compared with 16%; P < 0.0001); distal paresthesias (16% compared with 2%; P = 0.03); concentration difficulties (16% compared with 2%; P =0.03); and fatigue (26% compared with 9%; P = 0.04), and they had poorer global health status scores (P = 0.04). The Lyme group also had more abnormal joints (P = 0.02) and more verbal memory deficits (P = 0.01) than did the control group. Overall, 13 patients (34%; 95% Cl, 19% to 49%) had long-term sequelae from Lyme disease (arthritis or recurrent arthralgias [n = 6], neurocognitive impairment [n = 4], and neuropathy or myelopathy [n = 3]). Compared with controls, patients who had long-term sequelae had higher IgG antibody titers to the spirochete (P = 0.03) and received treatment later (34.5 months compared with 2.7 months; P < 0.0001). * Conclusions: Persons with a history of Lyme disease have more musculoskeletal impairment and a higher prevalence of verbal memory impairment when compared with those without a history of Lyme disease. Our findings suggest that disseminate Lyme disease may be associated with long-term morbidity., Patients who have had Lyme disease may have long-term effects such as joint pain and neurologic deficits. Lyme disease is a bacterial infection transmitted by ticks. Researchers studied 38 people who had had Lyme disease in the early 1980s and 43 people from the same area who had not (controls). Many of the previous Lyme disease patients had been infected for some time before treatment, and the antibiotics given were not the drugs now known to be most effective. Sixty-one percent of the patients with a history of Lyme disease reported joint pain, compared with 16% of controls. Neurological problems, such as burning or tingling sensations, concentration difficulties and memory loss, were also more common in those who had had Lyme disease. The previous Lyme disease patients also experienced more fatigue and poorer health in general than the controls. These findings may not apply to patients who are treated early with effective antibiotics.

Background Physician burnout has reached epidemic proportions. Although burnout is rooted in systems, practices for physician wellbeing and community can address exhaustion, burnout, and isolation. Inspired by the Japanese practice shinrin-yoku, forest therapy/bathing (FT) is a nature immersion practice that improves wellbeing in a group setting.Objective This program offered guided FT experiences to frontline faculty physicians in the Department of Medicine and evaluated potential for impact on burnout, resilience, and community.Methods Faculty physicians were recruited via email invitations to a free Forest Therapy group experience in the Arnold Arboretum in Boston, MA. Participants completed pre-and post-course surveys and evaluated its value as a community experience. Surveys measured burnout, resilience, and qualitative feedback on the experience.Results Twenty-seven faculty completed the baseline survey, twenty-three faculty participated, with 19 survey respondents. At baseline, 85% reported feeling burned out at least once a month. 46% reported feeling burned out more than a few times a month. 83% of participants responded that forest therapy could help them with the feeling of being burned out from work. Post-intervention, 100% of participants rated the experience as very or extremely valuable. 96% of participants reported they were interested in more frequent forest therapy sessions. 100% of participants would recommend this practice to other faculty. 70% of respondents reported the program could help them with burnout. Despite high baseline resilience, 94% of participants reported that forest therapy could help with stressful events and setbacks. Post-intervention, participants reported feeling relaxed, at peace, and calm.Conclusion This pilot demonstrates feasibility and acceptability for physicians of FT. Participants would consider recommending FT to their colleagues, and agreed that FT can help with wellbeing, and expressed enthusiasm for the community experience. This program may also be successfully incorporated into programs for leadership, teambuilding, and support after adverse events.

To use unbiased, data‐driven, principal component (PC) and cluster analysis to identify patient phenotypes of rheumatoid arthritis (RA) that might exhibit distinct trajectories of disease progression, response to treatment, and risk for adverse events. Patient demographic, socioeconomic, health, and disease characteristics recorded at entry into a large, single‐center, prospective observational registry cohort, the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS), were harmonized using PC analysis to reduce dimensionality and collinearity. The number of PCs was established by eigenvalue >1, cumulative variance, and interpretability. The resulting PCs were used to cluster patients using a K‐means approach. Longitudinal clinical outcomes were compared between the clusters over 2 years. Analysis of 142 variables from 1,443 patients identified 41 PCs that accounted for 77% of the cumulative variance in the data set. Cluster analysis distinguished 5 patient clusters: 1) less RA disease activity/multimorbidity, shorter RA duration, lower incidence of comorbidities; 2) less RA disease activity/multimorbidity, longer RA duration, more infections, psychiatric comorbidities, health care utilization; 3) moderate RA disease activity/multimorbidity, more neurologic comorbidity; 4) more RA disease activity/multimorbidity, shorter RA duration, more metabolic comorbidity, higher body mass index; 5) more RA disease activity/multimorbidity, longer RA duration, more hepatic, orthopedic comorbidity and RA‐related surgeries. The clusters exhibited differences in clinical outcomes over 2 years of follow‐up. Data‐driven analysis of the BRASS registry identified 5 distinct phenotypes of RA. These results illustrate the potential of data‐driven patient profiling as a tool to support personalized medicine in RA. Validation in an independent data set is ongoing.

BackgroundHemodynamic stress, conditioned by the morphology of the surrounding vasculature, plays an important role in aneurysm formation. Our goal was to identify image-based location-specific parameters that are associated with posterior communicating artery (PCoA) aneurysms.MethodsThree-dimensional morphological parameters obtained from CT angiography or digital subtraction angiography from 187 patients with unilateral PCoA aneurysms, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. In order to control for genetic and clinical risk factors, we chose the contralateral unaffected PCoA as a control group. We examined diameters and angles of the surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small aneurysms (≤5 mm) only and an unmatched analysis of 432 PCoA aneurysms and 197 control patients without PCoA aneurysms were also performed.ResultsIn a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 1.45×10−5, 95% CI 1.12×10−7to 1.88×10−3) and larger daughter-daughter angle (OR 1.04, 95% CI 1.02 to 1.07) were significantly associated with PCoA aneurysm presence after correcting for other variables. In subgroup analyses of small aneurysms (≤5 mm) and in an unmatched analysis the significance and direction of these results were preserved.ConclusionsLarger daughter-daughter angles and smaller diameter size ratio are significantly associated with the presence of PCoA aneurysms. These simple parameters can be utilized to guide the risk assessment for the formation of PCoA aneurysms in high risk patients.

ObjectiveTo compare the Clinical Disease Activity Index (CDAI) with the Routine Assessment of Patient Index Data 3 (RAPID3) from 2 large United States registries.MethodsUsing a cross section of clinic visits within 2 registries, we determined whether the outcome of each metric would place the patient in remission (REM), low (LDA), moderate (MDA), or high disease activity (HDA) using the CDAI, with the assumption that a patient in MDA or HDA would be a candidate for acceleration of treatment.ResultsWe identified significant disparities between the 2 indices in final disease categorization using each index system. For patients identified in LDA by CDAI, RAPID3 identified 20.4% and 28.3% as LDA in Corrona and the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS), respectively. For patients identified as MDA by CDAI, RAPID3 identified 36.2% and 31.1% as MDA in Corrona and BRASS, respectively, with the greatest disparities within each system identified for LDA and MDA activity by the CDAI (20.4% and 36.2% agreement of RAPID3 with CDAI, respectively, in Corrona and 28.3% and 31.1% agreement in BRASS). Overall comparison between CDAI and RAPID3 in the 4 disease categories resulted in estimated κ = 0.285 in both. The RAPID3 scores indicated the potential for treat-to-target acceleration in 34.4% of patients in REM or LDA based on CDAI in Corrona and 27.7% in BRASS, respectively.ConclusionThe RAPID3, based on patient-reported outcomes, shows differences with CDAI categories of disease activity. The components of CDAI are not highly correlated with RAPID3, except for patient global assessment. These differences could significantly affect the decision to advance treatment when using a treat-to-target regimen.

ObjectiveTo 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.MethodsThis 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.ResultsWe 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).ConclusionObesity, 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.

Seropositivity for anti–citrullinated protein antibody (ACPA)/rheumatoid factor (RF) in rheumatoid arthritis (RA) is associated with increased overall mortality; however, the association between antibody titers and mortality is not well established. Investigating relationships between antibody titers and mortality may clarify their role in RApathogenesis. This study was undertaken to evaluate the association of antibody titers with mortality and its modification by disease‐modifying antirheumatic drugs (DMARDs). Eligible patients with established RAwere identified through administrative claims data linked to laboratory results (2005–2016). Patients were categorized by positivity status for ACPA,RF, or both. Patients were further divided into groups by autoantibody titers. DMARD‐exposed patients were categorized into biologic DMARD(bDMARD) and conventional DMARD(cDMARD) subcohorts. Crude mortality rates/1,000 patient‐years and Kaplan‐Meier curves were compared between antibody categories. Adjusted Cox proportional hazards regression and sensitivity (propensity‐matched patients) analyses were conducted. Overall, 53,849 and 79,926 patients had evaluable ACPAand RFstatus, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA‐ and RF‐positive patients, respectively; P< 0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPAhazard ratio [HR] 1.60 [95% confidence interval (95% CI]) 1.45–1.76]; RF HR1.78 [95% CI1.66–1.91]). In cDMARD‐exposed patients, HRs were higher in seropositive versus seronegative cohorts; in bDMARD‐exposed patients, there was no difference in mortality by serostatus. Elevated ACPA/RFtiters were independently associated with increased mortality among patients with RAand persisted in patients treated with cDMARDs but not with bDMARDs.

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.

Background: Many patients with rheumatoid arthritis (RA) require a trial of multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) to control their disease. With the availability of several bDMARD options, the history of bDMARDs may provide an alternative approach to understanding subphenotypes of RA. The objective of this study was to determine whether there exist distinct clusters of RA patients based on bDMARD prescription history to subphenotype RA. Methods: We studied patients from a validated electronic health record-based RA cohort with data from January 1, 2008, through July 31, 2019; all subjects prescribed ≥ 1 bDMARD or targeted synthetic (ts) DMARD were included. To determine whether subjects had similar b/tsDMARD sequences, the sequences were considered as a Markov chain over the state-space of 5 classes of b/tsDMARDs. The maximum likelihood estimator (MLE)-based approach was used to estimate the Markov chain parameters to determine the clusters. The EHR data of study subjects were further linked with a registry containing prospectively collected data for RA disease activity, i.e., clinical disease activity index (CDAI). As a proof of concept, we tested whether the clusters derived from b/tsDMARD sequences correlated with clinical measures, specifically differing trajectories of CDAI. Results: We studied 2172 RA subjects, mean age 52 years, RA duration 3.4 years, and 62% seropositive. We observed 550 unique b/tsDMARD sequences and identified 4 main clusters: (1) TNFi persisters (65.7%), (2) TNFi and abatacept therapy (8.0%), (3) on rituximab or multiple b/tsDMARDs (12.7%), (4) prescribed multiple therapies with tocilizumab predominant (13.6%). Compared to the other groups, TNFi persisters had the most favorable trajectory of CDAI over time. Conclusion: We observed that RA subjects can be clustered based on the sequence of b/tsDMARD prescriptions over time and that the clusters were correlated with differing trajectories of disease activity over time. This study highlights an alternative approach to consider subphenotyping of patients with RA for studies aimed at understanding treatment response.

Background: To evaluate baseline hemoglobin (Hb) and radiographic progression over time in patients enrolled in the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS) registry. Methods: The BRASS is a prospective observational registry of patients with rheumatoid arthritis. BRASS Hb data and total sharp score data were matched with the main BRASS patients. Hb at baseline was categorized per the World Health Organization guidelines. Mean Hb, mean total sharp score, and mean changes over time from baseline to month 120 were summarized (overall, by low/normal Hb, and by current medication at baseline). All analyses were descriptive. Results: Out of the total (N= 1114) rheumatoid arthritis patients included in the analysis, patients with low Hb at baseline (n= 224 [20%]) had longer disease duration and higher disease activity and reported more pain compared with patients with normal Hb at baseline (n= 890 [80%]). Patients with low Hb at baseline continued to have lower Hb than patients with normal Hb throughout 10 years; although, on average, patients in the low Hb subgroup exhibited a steady increase in Hb levels. A larger increase in total sharp score over time was observed for patients with low Hb than for patients with normal Hb. No meaningful differences potentially attributable to medication at baseline were detected. Conclusions: Patients with low Hb levels at baseline tended to have increased radiographic progression as measured by total sharp score compared with patients with rheumatoid arthritis having normal Hb levels. Patients with low Hb experienced sustained improvements in Hb levels over time, regardless of the class of medication used. Trial registration: ClinicalTrials.gov NCT01793103.

Background: Vaccination against Lyme disease appears to be safe and effective; however, the cost per quality-adjusted life-year (QALY) gained with vaccination is unknown. Methods: We developed a decision-analytic model to evaluate the cost-effectiveness of vaccination compared with no vaccination in individuals living in endemic areas of Lyme disease. Our analysis encompassed a 10-year time horizon including a 2-year vaccination schedule with an additional year of vaccine effectiveness. The costs and probabilities of vaccination risk, compliance and efficacy, and Lyme disease clinical sequelae and treatment were estimated from the literature. Health-related quality-of-life weights of the various clinical sequelae of Lyme disease infection were obtained from a sample of 105 residents from Nantucket Island, Massachusetts. Results: Vaccinating 10 000 residents living in endemic areas with a probability of Lyme disease per season of 0.01 averted 202 cases of Lyme disease during a 10-year period. The additional cost per QALY gained compared with no vaccination was $62 300. Vaccination cost $12 600/QALY gained for endemic areas with an attack rate of 2.5% per season, and $145 200/QALY gained for an attack rate of 0.5%. Vaccinating individuals over an accelerated 2-month vaccination schedule improved the cost-effectiveness to $53 700/QALY gained. If a yearly booster shot is required for persisting efficacy, the marginal cost-effectiveness ratio increases to $72 700/ QALY. The cost-effectiveness of vaccination was most sensitive to the Lyme disease treatment efficacy and assumptions about the persistence of vaccination effect. Conclusion: Vaccination against Lyme disease appears only to-be economically attractive for individuals who have a seasonal probability of Borrelia burgdorferi infection of greater than 1%. Arch Intern Med. 2001;161:554-561

Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2– or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti–SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs.

Background: Previous follow-up studies of patients with Lyme disease suggest that disseminated infection may be associated with long-term neurologic and musculoskeletal morbidity. Objective: To determine clinical and functional outcomes in persons who were treated for Lyme disease in the late 1980s. Design: Population-based, retrospective cohort study. Setting: Nantucket Island, Massachusetts. Participants: 186 persons who had a history of Lyme disease (case-patients) and 167 persons who did not (controls). Measurements: Standardized medical history, physical examination, functional status measure (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]), mood state assessment (Profile of Mood States), neurocognitive tests, and serologic examination. Results: The prevalence of Lyme disease among adults on Nantucket Island was estimated to be 14.3% (95% CI, 9.3% to 19.1%). In multivariate analyses, persons with previous Lyme disease (mean time from infection to study evaluation, 6.0 years) had more joint pain (odds ratio for having joint pain in any joint, 2.1 [CI, 1.2 to 3.5]; P = 0.007), more symptoms of memory impairment (odds ratio for having any memory problem, 1.9 [CI, 1.1 to 3.5]; P = 0.003), and poorer functional status due to pain (odds ratio for 1 point on the SF-36 scale, 1.02 [CI, 1.01 to 1.03]; P [is less than] 0.001) than persons without previous Lyme disease. However, on physical examination, case-patients and controls did not differ in musculoskeletal abnormalities, neurologic abnormalities, or neurocognitive performance. Persons with previous Lyme disease who had persistent symptoms after receiving treatment (n = 67) were more likely than those who had completely recovered to have had fever, headache, photosensitivity, or neck stiffness during their acute illness (87% compared with 13%; odds ratio, 2.4 [CI, 1.0 to 5.5]; P = 0.045); however, the performance of the two groups on neurocognitive tests did not significantly differ. Conclusions: Because persons with previous Lyme disease exhibited no sequelae on physical examination and neurocognitive tests a mean of 6.0 years after infection, musculoskeletal and neurocognitive outcomes seem to be favorable. However, long-term impairment of functional status can occur., People with Lyme disease who are treated may have some recurring symptoms but will not develop serious musculoskeletal or neurologic problems. This was the conclusion of researchers who compared functional status and intellectual function in 186 people with a history of Lyme disease and 167 people who did not. There was no difference in intellectual function or musculoskeletal problems in the two groups. However, Lyme patients who were not successfully treated still had occasional symptoms such as fever, headache, photosensitivity or neck stiffness.

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Previous cross‐sectional studies have shown that rheumatoid arthritis (RA) patients with fibromyalgia (FM) have higher disease activity, greater medical costs, and worse quality of life compared to RApatients without FM. We determined the impact of FMon 2‐year changes in the functional status of RApatients in a prospective study. Subjects included participants in the Brigham Rheumatoid Arthritis Sequential Study who were enrolled in a substudy of the effects of pain in RA. Subjects completed questionnaires, including the Multi‐Dimensional Health Assessment Questionnaire (MDHAQ) and Polysymptomatic Distress (PSD) scale, semiannually, and underwent physical examination and laboratory tests yearly. Of the 156 included RAsubjects, 16.7% had FM, while 83.3% did not. In a multivariable linear regression model adjusted for age, sex, race, baseline MDHAQscore, disease duration, rheumatoid factor/cyclic citrullinated peptide antibody seropositivity, disease activity, and psychological distress, RApatients with FMhad a 0.14 greater 2‐year increase in MDHAQscore than RApatients without FM(P= 0.021). In secondary analyses examining the association between continuous PSDscale score and change in MDHAQ, higher PSDscale scores were significantly associated with greater 2‐year increases in MDHAQscore (β coefficient 0.013, P= 0.011). Both the presence of FMand increasing number of FMsymptoms predicted worsening of functional status among individuals with RA. Among individuals with RAand FM, the magnitude of the difference in changes in MDHAQwas 4‐ to 7‐fold higher than typical changes in MDHAQscore among individuals with established RA.

Patients with rheumatoid arthritis (RA) often ask whether specific foods, popularized as inflammatory or antiinflammatory, can improve or worsen their RA. Patients with RAtook a survey on diet and RAsymptoms, and the survey data were collected and analyzed. A dietary survey was mailed to 300 subjects in a single‐center RAregistry at a large academic center. Subjects were asked about their consumption of 20 foods and whether these foods make their RAsymptoms better, worse, or unchanged. Semiannual registry data include demographics, medications, comorbidities, and disease activity scores. Fisher's exact test and Wilcoxon's rank sum tests evaluated associations between subject characteristics from the most recent registry assessment and changes in RAsymptoms from specific foods. Of the 217 subjects (72% response rate), 83% were female; the median RAduration was 17 years (interquartile range 9–27 years), and 58% were taking a biologic disease‐modifying antirheumatic drug. Twenty‐four percent of subjects reported that foods affect their RAsymptoms, with 15% reporting improvement and 19% reporting worsening. Blueberries and spinach were the foods most often reported to improve RAsymptoms, while soda with sugar and desserts were those most often reported to worsen RAsymptoms. Younger age and noting that sleep, warm room temperature, and vitamin/mineral supplements improve RAwere each associated with reporting that foods affect RAsymptoms. Medication use, sex, body mass index, smoking, disease duration, disease activity scores, and self‐reported RAflares were not associated with reporting that foods affect RA. Nearly one‐quarter of RAsubjects with longstanding disease reported that diet had an effect on their RAsymptoms.

Patient registry data serves an increasing role in drug safety and comparative effectiveness research, but registry databases often do not contain confounder information measured at the same time that treatments begin. This study evaluated a set of approaches for estimating confounder values at treatment initiation using actual data from a rheumatoid arthritis (RA) registry to examine the risk of infection associated with different biologic DMARDs (bDMARDs). We examined the risk of infection associated with starting a TNF inhibitor (TNFi) versus any of the other non-TNFi bDMARDs. Different confounder assessment approaches were tested. All approaches were tested in Cox proportional hazard regression models that used a propensity score (PS). The confounder of interest was the disease activity score (DAS28-CRP). The confounder assessment approaches utilized different temporal relationships between the DAS28-CRP measurement and the start of the treatments of interest. We included 219 subjects with RA with 269 initiations of either a TNFi or a different bDMARD or both. Among this group, 305 infections were reported and confirmed through chart review. The hazard ratio (HR) for the risk of infection associated with use of a non-TNFi bDMARD ranged from 1.17 to 3.03 using 13 different approaches; only the approach with the highest HR produced results significantly different than one, but this approach included the fewest subjects and infections. The relative risk of infection for TNFi and other non-TNFi bDMARDs was similar using various approaches regarding which DAS28-CRP score should be used as the baseline measure in adjusted analyses.

To characterize physical activity participation (moderate‐to‐vigorous physical activity [MVPA], ≥150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week), to examine associations between disease activity and MVPA, and to identify MVPA correlates in adults with rheumatoid arthritis (RA) over 3 years. This study included 573 RA patients (94% white, 83% female, mean age 61 years, mean RA duration 19.5 years) with ≥1 annual registry visit and who completed the physical activity questionnaire. Baseline and annual measures included demographics/medical history, self‐efficacy for disease management, quality of life, patient/physician global assessment, physical function, and self‐reported physical activity. A logistic repeated‐measures model using the generalized estimating equation examined the relationship between disease activity and MVPA. Average disease activity (from the 3‐variable Disease Activity Score in 28 joints using the C‐reactive protein level) was mean ± SD 3.1 ± 1.4, 36% were physically inactive, and 29% met MVPA recommendations. There was a negative borderline association with disease activity (odds ratio [OR] 0.89 [95% confidence interval (95% CI) 0.79–1.00]). Correlates of meeting MVPA recommendations, adjusting for disease activity, were being white (OR 2.95 [95% CI 1.29–6.75]), older age (ages >69 years OR 0.58 [95% CI 0.36–0.92]), poor mental health (OR 0.63 [95% CI 0.41–0.95]), poor physical function (OR 0.59 [95% CI 0.34–1.01]), overweight/obese (body mass index [BMI] >25–30 OR 0.69 [95% CI 0.50–0.95], BMI >30–39.9 OR 0.60 [95% CI 0.41–0.88], and BMI ≤40 OR 0.24 [95% CI 0.08–0.74]), and patient global assessment (≥10–20 OR 0.57 [95% CI 0.39–0.83]). A small proportion of patients met MVPA recommendations despite well‐controlled disease. Disease activity was negatively associated with physical activity over time. Physical activity correlates were linked to lifestyle, mental health, and patient perceptions of disease, suggesting physical activity interventions that address patient perspectives may facilitate RA management.

Patient registries have contributed substantially to progress in clinical research in rheumatic diseases. However, not much is known about how to optimize the patient experience in such registries. We assessed patient views, motivations, and potential barriers towards participation in registry research to better understand how registries can be improved to maximize patient engagement. Focus groups were held with 23 patients (mean ± SD age 59 ± 13 years) from the Boston area and led by a bilingual moderator trained in focus group methodology, using a semistructured moderator guide. Three separate focus groups were conducted to thematic saturation: patients with rheumatoid arthritis (RA) who had registry experience, patients with any chronic illness, and Spanish‐speaking patients with RA or osteoarthritis. Patients in the latter 2 groups had no prior registry experience. Focus groups were audiotaped and transcribed. Four researchers independently analyzed transcripts using open data coding to identify themes. A normative group process was used to consolidate and refine themes. Seven major themes were identified, including personalization/convenience of data collection, trust and confidentiality, camaraderie, learning about yourself and your disease, altruism, material motivators, and capturing mental health and other elements of the lived experience. We observed distinct differences in the discussion content of the Spanish‐speaking patients compared to the English‐speaking patients. This study identified patient attitudes towards registry research among those with and without prior experience in a registry. The results provide insight into strategies for registry design to maximize patient engagement, which can lead to more robust registry data.

To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P= 0.0100) and CDAI ≤2.8 (−0.073; P= 0.0003) but not DAS28‐CRP <2.6 (−0.022; P= 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P< 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P< 0.0500) and 23–45% less likely to utilize DME (P< 0.0100). Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients.

We conducted an external validation study to examine the correlation of a previously published claims-based index for rheumatoid arthritis severity (CIRAS) with disease activity score in 28 joints calculated by using C-reactive protein (DAS28-CRP) and the multi-dimensional health assessment questionnaire (MD-HAQ) physical function score. Patients enrolled in the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) and Medicare were identified and their data from these two sources were linked. For each patient, DAS28-CRP measurement and MD-HAQ physical function scores were extracted from BRASS, and CIRAS was calculated from Medicare claims for the period of 365 days prior to the DAS28-CRP measurement. Pearson correlation coefficient between CIRAS and DAS28-CRP as well as MD-HAQ physical function scores were calculated. Furthermore, we considered several additional pharmacy and medical claims-derived variables as predictors for DAS28-CRP in a multivariable linear regression model in order to assess improvement in the performance of the original CIRAS algorithm. In total, 315 patients with enrollment in both BRASS and Medicare were included in this study. The majority (81%) of the cohort was female, and the mean age was 70 years. The correlation between CIRAS and DAS28-CRP was low (Pearson correlation coefficient = 0.07, P= 0.24). The correlation between the calculated CIRAS and MD-HAQ physical function scores was also found to be low (Pearson correlation coefficient = 0.08, P= 0.17). The linear regression model containing additional claims-derived variables yielded model R2of 0.23, suggesting limited ability of this model to explain variation in DAS28-CRP. In a cohort of Medicare-enrolled patients with established RA, CIRAS showed low correlation with DAS28-CRP as well as MD-HAQ physical function scores. Claims-based algorithms for disease activity should be rigorously tested in distinct populations in order to establish their generalizability before widespread adoption.

Objective.To investigate the associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis (RA).Methods.We conducted a prospective study consisting of 662 patients with RA who were followed up to 7 years from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study. Smoking and alcohol consumption were assessed through yearly questionnaires. The disease activity and functional status were measured annually by the Disease Activity Score examined in 28 commonly affected joints using C-reactive protein (DAS28-CRP3) and the Modified Health Assessment Questionnaire (MHAQ). Linear mixed models were developed to assess the longitudinal effects of smoking and alcohol consumption on DAS28-CRP3 and MHAQ after adjustment for potential confounders. The HLA-DRB1 shared epitope (HLA-SE) by smoking and alcohol interactions were also evaluated in the analysis.Results.The median followup time of the cohort was 4 years. Current smoking was not associated with DAS28-CRP3 in our study, but was associated with a higher MHAQ than nonsmokers with seropositive RA (p = 0.05). Alcohol consumption showed an approximate J-shaped relationship with MHAQ, with the minima occurring at 5.1–10.0 g/day. Compared to no alcohol use, alcohol consumption of 5.1–10.0 g/day was associated with a significant decrease of MHAQ (p = 0.02). When stratified by HLA-SE, the effect of alcohol consumption appeared to be stronger in HLA-SE–positive RA than HLA-SE–negative RA.Conclusion.We found that current smoking was associated with a worse functional status, while moderate alcohol consumption was associated with a better functional status in RA. Replications of these findings in other prospective studies are needed.

Objective.To describe the frequency, duration, and management of flares as reported by patients with rheumatoid arthritis (RA).Methods.Data were collected in a prospective observational study of patients with RA recruited from a single academic center and treated according to the rheumatologists’ discretion. Every 6 months, patients reported the number and duration of RA flares and described how these were managed in terms of adding or changing medication and use of nonpharmacologic strategies.Results.Of patients who reported flares at least once during the study, 74% reported having flares 6 months prior to study entry and 59% reported flares prior to the first 6-month visit. At subsequent visits, 54–57% reported having > 1 flare. Thirty percent of patients in remission reported flares. Flare duration lasted ≥ 2 weeks in 30%, 1–2 weeks in 13%, and < 1 week in 57%. Forty percent reported medication changes at the time of their flare; 16% changed medication and used nonpharmacologic strategies and 26% of patients reported no changes in treatment as a result of flares. Longer duration of flare was associated with changes in disease-modifying therapy.Conclusion.Patients with RA experienced flares more often when noted to be in higher disease activity states than when in remission and reported changes in disease-modifying antirheumatic drugs or biologics more frequently when flares were of longer duration. There is a need to prospectively study symptom intensity and duration of flare in relation to disease activity and consider self-management strategies in the development of a measure of flare.

Objective.Current recommendations advocate treatment with disease-modifying antirheumatic drugs (DMARD) in all patients with active rheumatoid arthritis (RA). We investigated the frequency of and reasons for inconsistent DMARD use among patients in a clinical rheumatology cohort.Methods.Patients in the Brigham Rheumatoid Arthritis Sequential Study were studied for DMARD use (any or none) at each semiannual study timepoint during the first 2 study years. Inconsistent use was defined as DMARD use at ≤ 40% of study timepoints. Characteristics were compared between inconsistent and consistent users (> 40%), and factors associated with inconsistent DMARD use were determined through multivariate logistic regression. A medical record review was performed to determine the reasons for inconsistent use.Results.Of 848 patients with ≥ 4 out of 5 visits recorded, 55 (6.5%) were inconsistent DMARD users. Higher age, longer disease duration, and rheumatoid factor negativity were statistically significant correlates of inconsistent use in the multivariate analyses. The primary reasons for inconsistent use identified through chart review, allowing for up to 2 co-primary reasons, were inactive disease (n = 28, 50.9%), intolerance to DMARD (n = 18, 32.7%), patient preference (n = 7, 12.7%), comorbidity (n = 6, 10.9%), DMARD not being effective (n = 3, 5.5%), and pregnancy (n = 3, 5.5%). During subsequent followup, 14/45 (31.1%) inconsistent users with sufficient data became consistent users of DMARD.Conclusion.A small proportion of patients with RA in a clinical rheumatology cohort were inconsistent DMARD users during the first 2 years of followup. While various patient factors correlate with inconsistent use, many patients re-start DMARD and become consistent users over time.

Objective.To conduct a proof-of-concept randomized trial of an Internal Family Systems (IFS) psychotherapeutic intervention on rheumatoid arthritis (RA) disease activity and psychological status.Methods.Patients with RA were randomized to either an IFS group for 9 months (n = 39) or an education (control) group (n = 40) that received mailed materials on RA symptoms and management. The groups were evaluated every 3 months until intervention end and 1 year later. Self-assessed joint pain (RA Disease Activity Index joint score), Short Form-12 physical function score, visual analog scale for overall pain and mental health status (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The 28-joint Disease Activity Score-C-reactive Protein 4 was determined by rheumatologists blinded to group assignment. Treatment effects were estimated by between-group differences, and mixed model repeated measures compared trends between study arms at 9 months and 1 year after intervention end.Results.Of 79 participants randomized, 68 completed the study assessments and 82% of the IFS group completed the protocol. Posttreatment improvements favoring the IFS group occurred in overall pain [mean treatment effects −14.9 (29.1 SD); p = 0.04], and physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were sustained 1 year later in self-assessed joint pain [−0.6 (1.1); p = 0.04], self-compassion [1.8 (2.8); p = 0.01], and depressive symptoms [−3.2 (5.0); p =0.01]. There were no sustained improvements in anxiety, self-efficacy, or disease activity.Conclusion.An IFS-based intervention is feasible and acceptable to patients with RA and may complement medical management of the disease. Future efficacy trials are warranted. ClinicalTrials.govidentifier: NCT00869349.