Publications by authors named "Michael D George"

89 Publications

Rheumatoid arthritis disease activity and hospitalized infection in a large U.S. registry.

Arthritis Care Res (Hoboken) 2022 Jul 22. Epub 2022 Jul 22.

University of Alabama at Birmingham, Division of Immunology and Rheumatology.

Objectives: The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities.

Methods: Using RA patients in the CorEvitas registry with Medicare coverage in 2006-2019, we identified eligible patients who had at least one visit with moderate disease activity based on the clinical disease activity index (CDAI>10 and <=22). Follow-up started at the subsequent CorEvitas visit. Hospitalized infection during follow-up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, low, and moderate disease activity and estimated the effect of time-varying CDAI on hospitalized infection by controlling for baseline and time-dependent confounders using marginal structural models (MSM).

Results: A total of 3,254 RA patients were eligible for analysis, among which 529 hospitalized infections were identified during follow-up. The crude incidence of hospitalized infection was 3.8 per 100 person years for patients in remission, 6.6 for low disease activity and 8.0 for moderate disease activity. Using MSMs, and compared to being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% CI: 1.13-2.28) and for moderate disease activity was 1.83 (95% CI: 1.30-2.64).

Conclusion: The risk of hospitalized infection was higher for RA patients in low or moderate disease activity compared to those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.
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http://dx.doi.org/10.1002/acr.24984DOI Listing
July 2022

Identifying Factors Associated With Treatment Response in Rheumatoid Arthritis Clinical Trials.

ACR Open Rheumatol 2022 Jun 30. Epub 2022 Jun 30.

Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA.

Objective: Despite a wealth of studies evaluating rheumatoid arthritis (RA) therapies, it remains difficult to compare efficacies across trials due to heterogeneous study populations. We sought to identify patient/trial characteristics associated with clinical response to enable fairer comparisons.

Methods: We reviewed 565 disease-modifying antirheumatic drug studies compiled for American College of Rheumatology (ACR) management guidelines. Seventy-two articles on randomized controlled phase II/III trials from 1995 to 2018 reporting the proportion of patients achieving 20%, 50% or 70% improvement in the ACR's RA disease score (ACR20/50/70) or Disease Activity Score-28 with erythrocyte sedimentation rate or C-reactive protein (DAS28-ESR or DAS28-CRP) with follow-up more than 3 months were included. We explored associations between 34 patient/trial characteristics and ACR responses. We constructed multivariable models using these factors to compute expected response rates and to compare observed with expected response rates across therapies.

Results: Among eligible clinical trials, later publication year, baseline DAS28-CRP score, methotrexate/biologic naivety, baseline ESR, follow-up of 52 weeks or more, number of subjects enrolled, and anticitrullinated peptide antibody seropositivity were associated with greater ACR response. Greater age, longer disease duration, higher baseline Sharp score, and steroid use were associated with lower response rates. Predictive models incorporating these factors explained 29%, 37%, and 53% of variance in ACR20, ACR50, and ACR70, respectively. Overall, comparing observed versus expected rates of response across trials more closely approximated results of head-to-head trials. For example, although observed responses numerically favored adalimumab to tofacitinib, comparison of observed versus expected results across trials more closely approximated the results from a head-to-head trial ("Oral Rheumatoid Arthritis triaL [ORAL] Strategy").

Conclusion: We identified factors associated with ACR response in RA trials. Adjusting for expected outcomes yielded therapy comparisons somewhat more similar to head-to-head trials. These findings could inform other across-trial comparisons, particularly when head-to-head trials are lacking.
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http://dx.doi.org/10.1002/acr2.11468DOI Listing
June 2022

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

J Arthroplasty 2022 Sep 19;37(9):1676-1683. Epub 2022 Jun 19.

University of Alabama at Birmingham and Veterans Affairs Medical Center, Birmingham, Alabama.

Objective: To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).

Methods: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.

Results: This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids.

Conclusion: This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.
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http://dx.doi.org/10.1016/j.arth.2022.05.043DOI Listing
September 2022

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

Arthritis Rheumatol 2022 Jun 20. Epub 2022 Jun 20.

University of Alabama at Birmingham and Veterans Affairs Medical Center, Birmingham, Alabama.

Objective: To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).

Methods: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.

Results: This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids.

Conclusion: This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.
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http://dx.doi.org/10.1002/art.42140DOI Listing
June 2022

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

Arthritis Care Res (Hoboken) 2022 Jun 19. Epub 2022 Jun 19.

University of Alabama at Birmingham and Veterans Affairs Medical Center, Birmingham, Alabama.

Objective: To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).

Methods: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.

Results: This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids.

Conclusion: This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.
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http://dx.doi.org/10.1002/acr.24893DOI Listing
June 2022

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

J Clin Rheumatol 2022 Aug 11;28(5):257-264. Epub 2022 Jun 11.

Division of Pulmonary, Allergy, and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA.

Background/objective: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF.

Methods: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models.

Results: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome.

Conclusion: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.
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http://dx.doi.org/10.1097/RHU.0000000000001847DOI Listing
August 2022

Adipocytokines and achievement of low disease activity in rheumatoid arthritis.

Semin Arthritis Rheum 2022 08 12;55:152003. Epub 2022 Apr 12.

Medicine Service, VA Nebraska-Western Iowa Health Care System and Department of Internal Medicine, Division of Rheumatology & Immunology, University of Nebraska Medical Center, Omaha, NE, United States.

Purpose: To determine if adipocytokines are independently associated with the achievement of low disease activity (LDA) over long-term follow-up in a large rheumatoid arthritis (RA) registry.

Methods: This cohort study evaluated adults with RA from the Veteran's Affairs RA Registry. Adipocytokines (adiponectin, leptin, and fibroblast growth factor [FGF]-21) and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum from enrollment. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox proportional hazard models evaluated associations between adipocytokines and rates of 1) DAS28 LDA and remission, 2) individual Boolean remission criteria and 3) initiation of a new bDMARD or tsDMARD.

Results: There were 1,276 participants with a DAS28 >3.2 at enrollment. Of these, 827 achieved LDA and 598 achieved remission over 2,287 and 4,096 person-years, respectively. Patients in the highest quartile of adiponectin had lower rates LDA before and after adjustment [aHR Q4: 0.68 (0.53,0.87) p<0.001]. Those in the highest quartile of leptin and FGF-21 also had lower rates of LDA. Higher quartiles of adipocytokines were also associated with lower rates of achieving a low patient/evaluator global scores and low tender joint counts. Among 1,236 biologic-naïve participants, values above the median for adiponectin [HR: 1.67 (1.23,1.26) p = 0.001] and FGF-21 [HR: 1.27 (1.09,1.47) p = 0.002] were associated with a greater likelihood of initiating a b/tsDMARD.

Conclusions: Adipocytokines may serve as prognostic biomarkers of a more severe RA disease course. Additional study is needed to determine whether adipocytokines are phenotypic markers or whether they actively promote disease progression.
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http://dx.doi.org/10.1016/j.semarthrit.2022.152003DOI Listing
August 2022

Elevations in Adipocytokines and Mortality in Rheumatoid Arthritis.

Rheumatology (Oxford) 2022 Mar 23. Epub 2022 Mar 23.

Medicine Service, VA Nebraska-Western Iowa Health Care System and Department of Internal Medicine, Division of Rheumatology & Immunology, University of Nebraska Medical Center, Omaha, NE.

Objectives: This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with rheumatoid arthritis (RA).

Methods: Participants were adults from the Veteran's Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrollment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality.

Results: A total of 2,583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower body mass index (BMI), autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use, and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrollment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs. lowest quartile) was associated with higher all-cause mortality [HR: 1.46 (95% CI: 1.11, 1.93) p = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75) p = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality.

Conclusions: Elevations in adipokines are associated with age, BMI, comorbidity, and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes.
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http://dx.doi.org/10.1093/rheumatology/keac191DOI Listing
March 2022

Circulating Adipokines and Associations with Incident Cardiovascular Disease in Rheumatoid Arthritis.

Arthritis Care Res (Hoboken) 2022 Mar 21. Epub 2022 Mar 21.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Objective: To assess whether circulating levels of adiponectin, leptin, and FGF-21 are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA).

Methods: Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism [VTE], CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted.

Results: Among 2,598 participants, 639 (25%) had at least one CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (HR: 1.39 [1.07-1.79], p=0.01) and CVD-related death (HR: 1.49 [1.16-1.92], p=0.002) but not other CVD events. High leptin was independently associated with CVD-related death (HR: 1.44 [1.05-1.97], p=0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR: 0.75 [0.58-0.97], p=0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in non-obese patients.

Conclusions: Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in non-obese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.
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http://dx.doi.org/10.1002/acr.24885DOI Listing
March 2022

Association between depression, anxiety, chronic pain, or opioid use and tumor necrosis factor inhibitor persistence in inflammatory arthritis.

Clin Rheumatol 2022 May 27;41(5):1323-1331. Epub 2022 Jan 27.

Department of Epidemiology and Biostatistics, Department of Medicine, Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Introduction: Depression, anxiety, and chronic pain are common comorbidities in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and may substantially impact patient outcomes. We aimed to determine whether these comorbidities were associated with earlier TNF-inhibitor (TNFi) discontinuation.

Methods: This retrospective cohort study using Optum's de-identified Clinformatics® Data Mart Database 2000-2014 identified patients with RA, PsA, and AS initiating a first TNFi. Depression/anxiety, chronic pain, and opioid use were identified using diagnosis codes and prescription fill data. Cox proportional hazards models were used to compare time to medication discontinuation in patients with or without each of these risk factors and to assess the additive effect of having multiple risk factors.

Results: Among 33,744 patients initiating a TNFi (23,888 RA, 6443 PsA, 3413 AS), depression/anxiety, chronic pain, and opioid use were common, with ≥ 1 risk factor in 48.1%, 42.5%, and 55.4% of patients with RA, PsA, and AS respectively. Each risk factor individually was associated with a 5-7-month lower median treatment persistence in each disease (all p < 0.001). Presence of multiple risk factors had an additive effect on time to discontinuation with HR (95% CI) 1.19 (1.14-1.24), 1.41 (1.33-1.49), and 1.47 (1.43-1.73) for 1, 2, or 3 risk factors respectively in RA. Findings were similar in PsA and AS.

Conclusions: Depression, anxiety, chronic pain, and opioid use are common in inflammatory arthritis and associated with earlier TNFi discontinuation. Recognizing and managing these risk factors may improve treatment persistence, patient outcomes, and cost of care. Key Points • Depression, anxiety, chronic pain, and opioid use are common in patients with inflammatory arthritis. • In patients initiating treatment with a TNF-inhibitor, depression, anxiety, chronic pain, or recent opioid use are associated with sooner discontinuation of TNFi therapy. • Patients with multiple of these risk factors are even more likely to discontinue therapy sooner.
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http://dx.doi.org/10.1007/s10067-021-06045-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058194PMC
May 2022

Patient Perceptions and Preferences Regarding Telemedicine for Autoimmune Rheumatic Diseases Care During the COVID-19 Pandemic.

Arthritis Care Res (Hoboken) 2022 07 13;74(7):1049-1057. Epub 2022 Apr 13.

Global Healthy Living Foundation, Upper Nyack, New York.

Objective: To assess the perceptions and preferences of telemedicine among patients with autoimmune rheumatic diseases during the COVID-19 pandemic.

Methods: We conducted an online survey among patients with autoimmune rheumatic diseases. Attitudes about telemedicine (i.e., telemedicine acceptability), evaluated using the validated Telemedicine Perception Questionnaire (TMPQ), and visit satisfaction were assessed for different telemedicine experiences and types of autoimmune rheumatic disease.

Results: Of 3,369 invitations, 819 responses were received. Participants had a mean ± SD age of 58.6 ± 11.6 years and were mostly White (n = 759, or 92.7%) and female (n = 702, or 85.7%). Of the 618 participants who said that telemedicine was available to them, 449 (72.7%) reported having a telemedicine visit, with 303 (67.5%) reporting attending a telemedicine video visit. On a 0 to 10 scale, the mean ± SD visit satisfaction score was 7.3 ± 1.8, with 25.8% of respondents being very satisfied (scores of 9 or 10). Video visits and higher TMPQ scores were associated with higher satisfaction. Compared to those who did not experience a telemedicine visit, patients who did were more likely to prefer telemedicine (video or phone) for routine visits (73.7% versus 44.3%; P < 0.001), reviewing test results (64.8% versus 53.8%; P < 0.001), when considering changing medications (40.5% versus 26.8%; P < 0.001), and when starting a new injectable medication (18.9% versus 12.7%; P = 0.02).

Conclusion: During the COVID-19 pandemic, patients with autoimmune rheumatic diseases frequently had telemedicine visits, with the majority held via video, and were satisfied with these visits. These results suggest that because patients prefer telemedicine for certain visit reasons, maximizing effective use of telemedicine will require personalized patient scheduling.
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http://dx.doi.org/10.1002/acr.24860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011874PMC
July 2022

Medication Interruptions and Subsequent Disease Flares During the COVID-19 Pandemic: A Longitudinal Online Study of Patients With Rheumatic Disease.

Arthritis Care Res (Hoboken) 2022 05 8;74(5):733-740. Epub 2022 Mar 8.

University of Pennsylvania, Philadelphia.

Objective: We aimed to assess trends in anxiety and interruptions in disease-modifying antirheumatic drug (DMARD) use among patients with rheumatic diseases during the COVID-19 pandemic and to evaluate whether DMARD interruptions were associated with disease flares.

Methods: ArthritisPower, the Vasculitis Patient-Powered Research Network, and other patient organizations invited members to join a 52-week longitudinal study, with baseline surveys completed March 29 to June 30, 2020, with follow-up through May 2021. Logistic regression incorporating generalized estimating equations evaluated associations between interruptions in DMARD use and self-reported disease flares at the next survey, adjusting for demographic characteristics, medications, disease, and calendar time.

Results: Among 2,424 patients completing a median of 5 follow-up surveys, the mean age was 57 years, 87% were female, and the most common conditions were rheumatoid arthritis, vasculitis, and psoriatic arthritis. Average Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety T scores decreased from April 2020 (58.7) to May 2021 (53.7) (P < 0.001 for trend). Interruptions in DMARD use decreased from April (11.2%) to December 2020 (7.5%) (P < 0.001) but increased through May 2021 (14.0%) (P < 0.001). Interruptions in DMARD use were associated with a significant increase in severe flares (rated ≥6 of 10) at the next survey (12.9% versus 8.0% [odds ratio (OR) 1.71 (95% confidence interval [95% CI 1.23, 2.36]) although not any flare (OR 1.18 [95% CI 0.89, 1.58])].

Conclusion: Anxiety and interruptions in DMARD use initially decreased over time, but DMARD interruptions increased during 2021, possibly related to an increase in COVID-19 cases or vaccine availability. Interruptions in DMARD use were associated with increased rates of severe disease flares, highlighting the importance of avoiding unnecessary DMARD interruptions.
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http://dx.doi.org/10.1002/acr.24837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011588PMC
May 2022

Risk of Serious Infection With Low-dose Glucocorticoids in Patients With Rheumatoid Arthritis: An Instrumental Variable Analysis.

Epidemiology 2022 01;33(1):65-74

From the Division of Rheumatology, University of Pennsylvania, Philadelphia, PA.

Background: Low-dose glucocorticoids are commonly used in the treatment of rheumatoid arthritis (RA). Observational studies have found an increased risk of serious infection associated with low-dose glucocorticoids, but concerns about residual confounding remain.

Methods: We identified adults with RA on stable immunomodulatory therapy for >6 months receiving no glucocorticoids or ≤5 mg/day using Medicare data from 2006 to 2015. We used provider preference for glucocorticoids as an instrumental variable (IV) to assess associations between low-dose glucocorticoid use and the risk of infection requiring hospitalization using a cause-specific proportional hazards model.

Results: We identified 163,603 qualifying treatment episodes among 120,656 patients. Glucocorticoids ≤5 mg/day were used by 25,373/81,802 (31.0%) of patients seen by a rheumatologist with low provider preference for glucocorticoids and by 36,087/81,801 (44.1%) of patients seen by a rheumatologist with high provider preference for glucocorticoids (adjusted odds ratio 1.81, 95% confidence interval 1.77, 1.84 for association between provider preference and glucocorticoids). Chronic obstructive pulmonary disease, opioids, antibiotics, previous emergency department visits, hospitalizations, and infections requiring hospitalization infections were unbalanced with regard to exposure but not to the IV. The incidence of infection requiring hospitalization was 8.0/100 person-years among patients unexposed to glucocorticoids versus 11.7/100 person-years among those exposed. The association between glucocorticoids and infection requiring hospitalization from IV analysis (hazard ratio 1.26 [1.02-1.56]) was similar to results from a standard multivariable model (hazard ratio 1.24 [1.21-1.28]).

Conclusions: Among patients with RA on stable immunomodulatory therapy, IV analysis based on provider preference demonstrated an increased risk of infection requiring hospitalization associated with low-dose glucocorticoids, similar to a traditional analysis.
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http://dx.doi.org/10.1097/EDE.0000000000001422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633063PMC
January 2022

Sarcopenic obesity in rheumatoid arthritis: prevalence and impact on physical functioning.

Rheumatology (Oxford) 2022 05;61(6):2285-2294

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Objective: We determined the prevalence of sarcopenic obesity in patients with RA using multiple methods and assessed associations with physical functioning.

Methods: This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the HAQ and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race and study.

Results: The prevalence of low lean mass and sarcopenic obesity was higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7-10%; 4-4.5%, respectively, all P <0.05). There was only moderate agreement among methods of sarcopenic obesity categorization (Kappa 0.45). The recently validated method categorized fewer subjects as obese, and many of these were categorized as low lean mass only. Low lean mass, obesity and sarcopenic obesity were each associated with higher HAQ and lower SPPB at baseline and numerically greater worsening.

Conclusion: RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.
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http://dx.doi.org/10.1093/rheumatology/keab710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157125PMC
May 2022

Adipocytokines and Associations with Abnormal Body Composition in Rheumatoid Arthritis.

Arthritis Care Res (Hoboken) 2021 Sep 24. Epub 2021 Sep 24.

Columbia University, New York, NY, USA.

Purpose: We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA).

Methods: Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age, sex, and race-specific Z-Scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor(FGF)-21 were assessed using linear and logistic regression models adjusting for demographics and study cohort. We also determined the improvement in the area-under-the-curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographics, study, and body mass index (BMI).

Results: Among 419 participants, older age was associated with higher levels of all adipokines while higher C-reactive protein was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographics, study, and BMI (AUC 0.75 v. 0.66).

Conclusions: Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.
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http://dx.doi.org/10.1002/acr.24790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942864PMC
September 2021

Improving benefit-harm assessment of glucocorticoid therapy incorporating the patient perspective: The OMERACT glucocorticoid core domain set.

Semin Arthritis Rheum 2021 10 25;51(5):1139-1145. Epub 2021 Jun 25.

Discipline of Medicine, Faculty of Health and Medical Sciences, The University of Adelaide, South Australia, Australia, Rheumatology Research Group, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.

Objective: Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions.

Methods: The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set.

Results: 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as "mandatory in specific circumstances". The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders.

Conclusion: A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.
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http://dx.doi.org/10.1016/j.semarthrit.2021.06.010DOI Listing
October 2021

Investigating changes in disease activity as a mediator of cardiovascular risk reduction with methotrexate use in rheumatoid arthritis.

Ann Rheum Dis 2021 11 28;80(11):1385-1392. Epub 2021 May 28.

Medicine & Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA

Objective: Examine the association of methotrexate (MTX) use with cardiovascular disease (CVD) in rheumatoid arthritis (RA) using marginal structural models (MSM) and determine if CVD risk is mediated through modification of disease activity.

Methods: We identified incident CVD events (coronary artery disease (CAD), stroke, heart failure (HF) hospitalisation, CVD death) within a multicentre, prospective cohort of US Veterans with RA. A 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) was collected at regular visits and medication exposures were determined by linking to pharmacy dispensing data. MSMs were used to estimate the treatment effect of MTX on risk of incident CVD, accounting for time-varying confounders between receiving MTX and CVD events. A mediation analysis was performed to estimate the indirect effects of methotrexate on CVD risk through modification of RA disease activity.

Results: Among 2044 RA patients (90% male, mean age 63.9 years, baseline DAS28-CRP 3.6), there were 378 incident CVD events. Using MSM, MTX use was associated with a 24% reduced risk of composite CVD events (HR 0.76, 95% CI 0.58 to 0.99) including a 57% reduction in HF hospitalisations (HR 0.43, 95% CI 0.24 to 0.77). Individual associations with CAD, stroke and CVD death were not statistically significant. In mediation analyses, there was no evidence of indirect effects of MTX on CVD risk through disease activity modification (HR 1.03, 95% CI 0.80 to 1.32).

Conclusions: MTX use in RA was associated with a reduced risk of CVD events, particularly HF-related hospitalisations. These associations were not mediated through reductions in RA disease activity, suggesting alternative MTX-related mechanisms may modify CVD risk in this population.
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http://dx.doi.org/10.1136/annrheumdis-2021-220125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516691PMC
November 2021

Disruptions in Rheumatology Care and the Rise of Telehealth in Response to the COVID-19 Pandemic in a Community Practice-Based Network.

Arthritis Care Res (Hoboken) 2021 08 6;73(8):1153-1161. Epub 2021 Jul 6.

University of Alabama at Birmingham.

Objective: The effect of the COVID-19 pandemic on community-based rheumatology care and the use of telehealth is unclear. We undertook this study to investigate the impact of the pandemic on rheumatology care delivery in a large community practice-based network.

Methods: Using a community practice-based rheumatologist network, we examined trends in in-person versus telehealth visits versus canceled visits in 3 time periods: pre-COVID-19, COVID-19 transition (6 weeks beginning March 23, 2020), and post-COVID-19 transition (May-August). In the transition period, we compared patients who received in-person care versus telehealth visits versus those who cancelled all visits. We used multivariable logistic regression to identify factors associated with canceled or telehealth visits.

Results: Pre-COVID-19, there were 7,075 visits/week among 60,002 unique rheumatology patients cared for by ~300 providers practicing in 92 offices. This number decreased substantially (24.6% reduction) during the COVID-19 transition period for in-person visits but rebounded to pre-COVID-19 levels during the post-COVID-19 transition. There were almost no telehealth visits pre-COVID-19, but telehealth increased substantially during the COVID-19 transition (41.4% of all follow-up visits) and slightly decreased during the post-COVID-19 transition (27.7% of visits). Older age, female sex, Black or Hispanic race/ethnicity, lower socioeconomic status, and rural residence were associated with a greater likelihood of canceling visits. Most factors were also associated with a lower likelihood of having telehealth versus in-office visits. Patients living further from the rheumatologists' office were more likely to use telehealth.

Conclusion: COVID-19 led to large disruptions in rheumatology care; these disruptions were only partially offset by increases in telehealth use and disproportionately affected racial/ethnic minorities and patients with lower socioeconomic status. During the COVID-19 era, telehealth continues to be an important part of rheumatology practice, but disparities in access to care exist for some vulnerable groups.
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http://dx.doi.org/10.1002/acr.24626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212120PMC
August 2021

Treatment Strategies for Patients With Immune-Mediated Inflammatory Diseases.

JAMA 2021 05;325(17):1726-1728

University of Pennsylvania Medical Center, Philadelphia.

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http://dx.doi.org/10.1001/jama.2021.2740DOI Listing
May 2021

Social Distancing, Health Care Disruptions, Telemedicine Use, and Treatment Interruption During the COVID-19 Pandemic in Patients With or Without Autoimmune Rheumatic Disease.

ACR Open Rheumatol 2021 Jun 2;3(6):381-389. Epub 2021 May 2.

University of Alabama at Birmingham.

Background: We aimed to compare concerns, social distancing, health care disruptions, and telemedicine use in patients with autoimmune rheumatic disease (ARD) and non-ARD and to evaluate factors associated with immunomodulatory medication interruptions.

Methods: Patients in a multistate community rheumatology practice network completed surveys from April 2020 to May 2020. Adults with common ARD (rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus) or non-ARD (gout, osteoarthritis, osteoporosis) were evaluated. Concerns about coronavirus disease 2019 (COVID-19), social distancing, health care disruptions, and telemedicine use were compared in patients with ARD versus non-ARD, adjusting for demographics, rural residence, and zipcode-based measures of socioeconomic status and COVID-19 activity. Factors associated with medication interruptions were assessed in patients with ARD.

Results: Surveys were completed by 2319/36 193 (6.4%) patients with non-ARD and 6885/64 303 (10.7%) with ARD. Concerns about COVID-19 and social distancing behaviors were similar in both groups, although patients receiving a biologic or Janus kinase (JAK) inhibitor reported greater concerns and were more likely to avoid friends/family, stores, or leaving the house. Patients with ARD were less likely to avoid office visits (45.2% vs. 51.0%, odds ratio [OR] 0.79 [0.70-0.89]) with similar telemedicine use. Immunomodulatory medications were stopped in 9.7% of patients with ARD, usually (86.9%) without a physician recommendation. Compared with patients with an office visit, the likelihood of stopping medication was higher for patients with a telemedicine visit (OR 1.54 [1.19-1.99]) but highest for patients with no visits (OR 2.26 [1.79-2.86]).

Conclusion: Patients with ARD and non-ARD reported similar concerns about COVID-19 and similar social distancing behaviors. Missed office visits were strongly associated with interruptions in immunomodulatory medication.
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http://dx.doi.org/10.1002/acr2.11239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207682PMC
June 2021

A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies.

Rheumatology (Oxford) 2021 06;60(6):2615-2628

Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Objectives: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening.

Methods: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review.

Results: Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers.

Conclusion: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.
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http://dx.doi.org/10.1093/rheumatology/keab166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213426PMC
June 2021

Risk for infections with glucocorticoids and DMARDs in patients with rheumatoid arthritis.

RMD Open 2021 02;7(1)

Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Immunomodulatory therapy for rheumatoid arthritis (RA) carries risk for infectious complications. Understanding the risks of different therapeutic options is essential for making treatment decisions and appropriately monitoring patients. This review examines data on the risks for serious infections and other key infections of interest for the major classes of agents in use for RA: glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologics and Janus kinase (JAK) inhibitors. Conventional synthetic DMARDs have an excellent safety profile with recent data available supporting the relative safety of methotrexate. Tumour necrosis factor (TNF) inhibitors are associated with an increase in the risk of serious infections. Risk with other biological agents and with JAK inhibitors varies somewhat but overall appears similar to that of TNF inhibitors, with JAK inhibitors also associated with a greater risk of herpes zoster. Glucocorticoids have a dose-dependent effect on serious infection risk-at higher doses risk of infection with glucocorticoids is substantially greater than with other immunomodulatory therapies, and even low-dose therapy carries a risk of infection that appears to be similar to that of biological therapies.
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http://dx.doi.org/10.1136/rmdopen-2020-001235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893655PMC
February 2021

Web Exclusive. Annals On Call - Low-Dose Steroids and Risk for Infection.

Ann Intern Med 2021 Jan;174(1):OC2

University of Pennsylvania, Philadelphia, Pennsylvania (M.D.G.).

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http://dx.doi.org/10.7326/A20-0005DOI Listing
January 2021

Alcohol Compliance Checks and Underage Alcohol-Involved Crashes: Evaluation of a Statewide Enforcement Program in South Carolina from 2006 to 2016.

Alcohol Clin Exp Res 2021 01 18;45(1):242-250. Epub 2020 Dec 18.

Prevention Research Center, (HDH), Pacific Institute for Research and Evaluation, Berkeley, California.

Objective: This research evaluated the South Carolina Alcohol Enforcement Team impact for reducing retail alcohol access to underage persons to decrease drinking and driving crashes among that population.

Methods: The natural research experiment used interrupted time-series (ITS) analyses of drinking and driving crashes involving under 21-year-old drivers from July 2006 through December 2016 (126-month period = 4,782 Driving Under Influence [DUI] crashes for under 21-year-old drivers, µ = 38 crashes per month). Additional data analyzed included the monthly total number of retail compliance checks (total during 126-month period = 64,954 compliance checks completed, µ = 515.5 checks per month), the average percentage of underage alcohol purchases (total completed during 126-month period = 8,814 purchases, µ = 70 purchases per month), and a calculated measure of the percent of the population under 21 years old exposed to compliance checks each month. We used drinking and driving crashes for 21-year-old and over drivers as a control time series (total number over a 126-month period = 52,180 DUI crashes for 21 and older drivers, µ = 414.1 crashes per month).

Results: The results show a decline in drinking and driving crashes for drivers under 21 when compliance checks increase, and when compliance checks decline, traffic crashes increase. Stable Alcohol Enforcement Team implementation over 78 months produced an overall 18 to 29% decline in such crashes. A visual examination of the crash time series demonstrated that under-21-age-driver crashes declined during the first wave of implementation and increased following a lag when enforcement declined, which provided additional empirical support for a South Carolina Alcohol Enforcement Team impact on retail alcohol availability. An ITS analysis of the prestable period compared to the stable period was statistically significant (T = -3.78, p < 0.001). A cross-check of these results using single-vehicle nighttime crashes using identical Autoregressive Integrated Moving Average models was also statistically significant (T = -8.18, p < 0.001).

Conclusions: This longitudinal study provides strong evidence of sustained reductions in alcohol availability to underage youth can subsequently reduce alcohol-related traffic crashes. Reductions found in this study continued over several years, considerably longer than any previous equivalent research has shown.
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http://dx.doi.org/10.1111/acer.14507DOI Listing
January 2021

Evaluation of the impact of age and adiposity on a multi-biomarker disease activity score before and after adjustment.

Clin Rheumatol 2021 Jun 25;40(6):2419-2426. Epub 2020 Nov 25.

University of Pennsylvania, Philadelphia, PA, USA.

Purpose: We assessed the impact of adjustment of the multi-biomarker disease activity score (MBDA) for age, sex, and leptin, over the range of age and adiposity, and assessed relationships with clinical disease activity.

Methods: Patients with RA, ages 18-75 years, were recruited from clinical practices and completed whole-body DXA to quantify fat mass indices (FMI, kg/m). FMI Z-scores were calculated based on distributions in a reference population. Descriptive statistics described relationships between age, FMI Z-score, and the original MBDA and adjusted MBDA (aMBDA). Swollen joint counts (SJC) and the clinical disease activity index (CDAI) were assessed over MBDA categories.

Results: There were 104 participants (50% female) with mean (SD) age of 56.1 (12.5) and body mass index (BMI) of 28.8 (6.9). Older age was associated with higher MBDA scores in men. The aMBDA was not associated with age. The original MBDA score was associated with FMI Z-score among women (Rho = 0.42, p = 0.002) but not men. The aMBDA was not associated with FMI Z-score in either women or men. The aMBDA score was lower than the original MBDA in the highest quartile of FMI in women and was higher in the lowest FMI quartiles in women and men. CDAI, SJC, and radiographic scores were similar across activity categories for the original MBDA score and aMBDA.

Conclusions: The aMBDA demonstrated reduced associations with adiposity, particularly among women. The aMBDA may be less likely to overestimate disease activity in women with greater adiposity and to underestimate disease activity in men and women with lesser adiposity. Key Points • Leptin adjustment of the MBDA score reduces the influence of adiposity, particularly among women. • Leptin adjustment results in significantly higher estimated disease activity in thin men and women. • The adjusted and unadjusted score correlate similarly with clinical disease activity measures.
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http://dx.doi.org/10.1007/s10067-020-05508-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127402PMC
June 2021

Concerns, Healthcare Use, and Treatment Interruptions in Patients With Common Autoimmune Rheumatic Diseases During the COVID-19 Pandemic.

J Rheumatol 2021 04 15;48(4):603-607. Epub 2020 Nov 15.

S. Venkatachalam, PhD, MPH, K. Gavigan, MPH, D. Curtis, BA, W.B. Nowell, PhD, MSW, Global Healthy Living Foundation, Upper Nyack, New York.

Objective: To assess concerns and healthcare-related behaviors of patients with autoimmune rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Adults from the United States with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) from the ArthritisPower Patient-Powered Research Network and CreakyJoints patient community completed surveys. Concerns and behaviors were compared among patients with different autoimmune conditions, disease-modifying antirheumatic drug (DMARD) use, and geographic measures of urban status, income, education, and COVID-19 activity.

Results: Among 1517 participants (925 RA, 299 PsA, 185 AS, 108 SLE), mean age was 55.1 years, 88.3% were female, and 89.5% were White. COVID-19 concerns were similar across the country and were higher in biologic users ( < 0.001). Avoidance of doctor's office visits (56.6%) or laboratory testing (42.3%) and use of telehealth (29.5%) were more common in urban areas. Among participants receiving a DMARD without COVID-19 or other respiratory illness, 14.9% stopped a DMARD, with 78.7% of DMARD interruptions not recommended by a physician. DMARD stopping was more common in participants with lower socioeconomic status (SES) and in participants who avoided an office visit (OR 1.46, 95% CI 1.04-2.04) or reported lack of telehealth availability OR 2.26 (95% CI 1.25-4.08).

Conclusion: In the early months of the COVID-19 pandemic, patients with RA, PsA, AS, and SLE frequently avoided office visits and laboratory testing. DMARD interruptions commonly occurred without the advice of a physician and were associated with SES, office visits, and telehealth availability, highlighting the need for adequate healthcare access and attention to vulnerable populations during the pandemic.
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http://dx.doi.org/10.3899/jrheum.201017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121899PMC
April 2021

Association of cell phone location data and trends in COVID-19 infections during loosening of stay-at-home restrictions.

J Travel Med 2020 12;27(8)

Division of Rheumatology, Department of Medicine, University of Pennsylvania, 5 White Building 3400 Spruce Street, Philadelphia, PA 19104, USA.

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http://dx.doi.org/10.1093/jtm/taaa177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543593PMC
December 2020

Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study.

Ann Intern Med 2020 12 22;173(11):870-878. Epub 2020 Sep 22.

University of Alabama at Birmingham, Birmingham, Alabama (L.C., F.X., H.Y., J.R.C.).

Background: Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain.

Objective: To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy.

Design: Retrospective cohort study.

Setting: Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.

Patients: Adults with RA receiving a stable DMARD regimen for more than 6 months.

Measurements: Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models.

Results: 247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all < 0.001 vs. no glucocorticoids).

Limitation: Potential for residual confounding and misclassification of glucocorticoid dose.

Conclusion: In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk.

Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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http://dx.doi.org/10.7326/M20-1594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073808PMC
December 2020

The Impact of Obesity on Disease Activity and Treatment Response in Rheumatoid Arthritis.

Curr Rheumatol Rep 2020 08 1;22(9):56. Epub 2020 Aug 1.

Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA.

Purpose Of The Review: A growing number of studies have suggested that disease outcomes and response to therapy may be different in patients with rheumatoid arthritis (RA) who are obese. The goal of this review is to examine the most recent literature, with a focus on the impact of obesity on the assessment of disease activity and treatment outcomes in RA.

Recent Findings: Obesity is common in patients with RA and can have a substantial impact on patient symptoms and outcomes. Obesity is associated with higher rates of chronic pain and opiate use, elevated inflammatory markers, and less reliable physical exam findings, making assessment of disease activity and treatment response more challenging. Despite seemingly worse clinical disease activity, evidence has accumulated demonstrating that obese patients with RA have less inflammation by imaging and lower rates of radiographic progression over time. Whether obesity influences the effectiveness of specific therapies remains controversial. Obesity is very common and is associated with more severe symptoms and higher rates of disability among RA patients. While clinical disease activity is frequently observed to be higher in obese patients with RA, it remains unclear whether poorer treatment response rates in this setting are related to reduced efficacy of therapies or are an artifact of biases in the accurate assessment of the disease.
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http://dx.doi.org/10.1007/s11926-020-00933-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025781PMC
August 2020
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