Abstract
In this issue of the Journal, Wei et al. (Am J Epidemiol. 2023;192(9):1432–1448); demonstrate the modification of effect of nonselective nonsteroidal antiinflammatory drugs in the setting of ...aspirin use for the outcome of cardiovascular events. This study is distinctive in its aim to compare 2 similar therapies in the setting of 2 clinical scenarios (aspirin use vs. not) based on some mechanistic rationale. The use of an active comparator design with a prehypothesized evaluation of treatment heterogeneity can provide compelling evidence to support relevant clinical decisions for which clinical trial evidence is not likely or possible.
Objective
Rheumatoid arthritis (RA) and its treatments are associated with an increased risk of infection, but it remains unclear whether these factors have an impact on the risk or severity of ...COVID‐19. The present study was undertaken to assess the risk and severity of COVID‐19 in a US Department of Veterans Affairs (VA) cohort of patients with RA and those without RA.
Methods
A matched cohort study using national VA data was conducted. Patients diagnosed as having RA were identified among nondeceased individuals who were active in the VA health care system as of January 1, 2020 and who had received care in a VA medical center in 2019; patients for whom no RA diagnostic code was indicated were matched to the RA patients (1:1) by age, sex, and VA site (non‐RA controls). Patients diagnosed as having COVID‐19 and those with severe COVID‐19 (defined as requiring hospitalization or leading to death) were ascertained from a national VA COVID‐19 surveillance database through December 10, 2020. Multivariable Cox models were used to compare the risk of COVID‐19 and COVID‐19 hospitalization or death between RA patients and non‐RA controls, after adjusting for demographic characteristics, comorbidities, health care utilization and access, and county‐level COVID‐19 incidence rates.
Results
This VA cohort of RA patients and non‐RA controls (n = 33,886 subjects per group) predominantly comprised male patients (84.5%), and the mean age was 67.8 years. During follow‐up, 1,503 patients in the cohort were diagnosed as having COVID‐19; among them, 388 patients had severe COVID‐19 (hospitalization or death), while in 228 patients, the deaths were not related to COVID‐19. In the multivariable model, RA was associated with a higher risk of COVID‐19 (adjusted hazard ratio HR 1.25 95% confidence interval (95% CI) 1.13–1.39) and a higher risk of COVID‐19 hospitalization or death (adjusted HR 1.35 95% CI 1.10–1.66) as compared to non‐RA controls. Use of disease‐modifying antirheumatic drugs and prednisone, as well as self‐reported Black race, self‐reported Hispanic ethnicity, and presence of several chronic conditions, but not seropositivity for RA autoantibodies, were each associated with risk of COVID‐19 and severe COVID‐19 (hospitalization or death).
Conclusion
Patients with RA are at higher risk of developing COVID‐19 and severe COVID‐19 (leading to hospitalization or death) compared to those without RA. With a risk of COVID‐19 that approaches that of other recognized chronic conditions, these findings suggest that RA patients should be prioritized for COVID‐19 prevention and management strategies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although there is a substantial body of literature focused on understanding noninhalational risk-factors for rheumatoid arthritis, the data are mixed and often conflicting. Given the other health ...benefits for certain lifestyle modifications, it seems reasonable for clinicians to promote healthy lifestyle habits related to diet, exercise, maintenance of health weight, and maintenance of good dental hygiene. Overall, however, these lifestyle modifications may be expected to have modest benefit, and other strategies to prevent rheumatoid arthritis in high-risk patients are needed.
Objective
Fluctuations in weight have been linked to cardiovascular (CV) outcomes in the general population. The present study was undertaken to evaluate whether weight fluctuation was independently ...predictive of CV events in patients with rheumatoid arthritis (RA).
Methods
We studied patients with RA from the Corrona registry. Weight change was categorized as loss of ≥10%, loss of 5–10%, stable, gain of 5–10%, and gain of ≥10%. We also categorized patients by quintile of variability in weight in prior observation periods. Cox proportional hazards models explored independent associations between time‐varying weight change and weight variability and risk of CV events before and after adjusting for CV risk factors, RA disease features, and disability.
Results
Among 31,381 participants, those who lost or gained 10% of their weight had greater disease activity and worse physical function, and they were more likely to smoke, have diabetes mellitus, receive corticosteroids, and be disabled. In adjusted models, a greater risk of CV events was observed in those who experienced 10% weight loss (hazard ratio HR 1.18 95% confidence interval (95% CI) 1.03–1.36, P = 0.02) or weight gain (HR 1.20 95% CI 1.04–1.38, P = 0.01). The association between weight change and CV events was stronger among participants with body mass index <25 kg/m2 for 10% weight loss (HR 1.34 95% CI 1.08–1.66, P = 0.001 and 10% weight gain (HR 1.74 95% CI 1.41–2.24, P < 0.001). Patients with greater variability in weight had a higher risk of CV events.
Conclusion
Recent changes and high variability in weight predict CV events in RA, particularly among thin patients. Further study is necessary to determine if weight fluctuation has adverse cardiometabolic consequences that are independent of other risk factors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
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.
Retrospective cohort study.
Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.
Adults with RA receiving a stable DMARD regimen for more than 6 months.
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.
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).
Potential for residual confounding and misclassification of glucocorticoid dose.
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.
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
People with rheumatoid arthritis (RA) have both disease-specific risk factors for osteoporosis and fractures in addition to those that affect the general population. Disease specific risks include ...directly pathogenic auto-antibodies, chronic exposure to systemic inflammation, and joint damage causing early disability. Risk factors that affect the general population which may have a higher prevalence in RA include smoking, calcium and vitamin D deficiency as well as hypogonadism. Additionally, chronic exposure to glucocorticoids results in reduced bone mineral density and body composition changes which can further increase fracture risk. In this review we discuss these risk-factors for osteoporosis as well as factors that may impact fall and fracture risk in people with RA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
To define the minimum clinically important improvement (MCII) and minimum clinically important worsening (MCIW) for the Patient Activity Scale II (PAS‐II; range 0–10), a recommended ...patient‐reported outcome measuring rheumatoid arthritis disease activity.
Methods
Data were taken from Forward, The National Databank for Rheumatic Diseases, from four 6‐month data collection periods. Both anchor‐based and distribution‐based methods were used to estimate the MCII and MCIW. Anchor‐based analyses used comparisons of pain and general health to the previous 6 months. Distribution‐based analyses used 0.5 and 0.35 SDs. We stratified analyses based on the PAS‐II score (above/below 3.7), hypothesizing that the MCII and MCIW would depend on the baseline score. To assess construct validity, we evaluated the odds of achieving the MCII in patients receiving new therapies.
Results
In the overall sample, for pain and general health anchor questions, the MCIW was 0.50 and 0.55, respectively. The MCII was defined as 0.39 and 0.45, respectively, for pain and general health. The MCIW for anchor‐based methods among participants with low disease activity was 1.10 (1.09/1.11 pain/general health), while the MCII for those with moderate‐to‐high disease activity was 1.09 (1.15/1.02 pain/general health). Distribution‐based methods for 0.5 and 0.35 SD were 1.08 and 0.76, respectively, for pain and general health. There was fair‐to‐excellent agreement with clinically important differences in assessments of pain and disability. Patients receiving new treatments had 30% greater odds of achieving the MCII.
Conclusion
The minimum important change in PAS‐II score was approximately 0.5. Among participants with a moderate‐to‐high PAS‐II score , the MCII was 1.1, and among participants with low disease activity, the MCIW was 1.1.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Previous reports have suggested that transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reduced by higher temperatures and higher humidity. We analyzed case data from the ...United States to investigate the effects of temperature, precipitation, and ultraviolet (UV) light on community transmission of SARS-CoV-2.
Daily reported cases of SARS-CoV-2 across the United States from 22 January 2020 to 3 April 2020 were analyzed. We used negative binomial regression modeling to determine whether daily maximum temperature, precipitation, UV index, and the incidence 5 days later were related.
A maximum temperature above 52°F on a given day was associated with a lower rate of new cases at 5 days (incidence rate ratio IRR, 0.85 0.76, 0.96; P = .009). Among observations with daily temperatures below 52°F, there was a significant inverse association between the maximum daily temperature and the rate of cases at 5 days (IRR, 0.98 0.97, 0.99; P = .001). A 1-unit higher UV index was associated with a lower rate at 5 days (IRR, 0.97 0.95, 0.99; P = .004). Precipitation was not associated with a greater rate of cases at 5 days (IRR, 0.98 0.89, 1.08; P = .65).
The incidence of disease declines with increasing temperature up to 52°F and is lower at warmer vs cooler temperatures. However, the association between temperature and transmission is small, and transmission is likely to remain high at warmer temperatures.
Osteoporosis and fractures in rheumatoid arthritis Wysham, Katherine D; Baker, Joshua F; Shoback, Dolores M
Current opinion in rheumatology,
2021-May-01, 2021-05-00, Volume:
33, Issue:
3
Journal Article
Rheumatoid arthritis (RA) is associated with increased risk for osteoporotic fracture. We highlight RA-specific risk factors for bone mineral density (BMD) loss and fractures and considerations ...regarding the diagnosis and treatment of osteoporosis in patients with RA.
Anticitrullinated protein antibody (ACPA) positivity, although associated with low BMD in early RA, is not associated with accelerated BMD loss over time when compared to ACPA negative individuals. Studies have found reduced BMD in individuals on low doses of glucocorticoids (GCs). Poor functional status and frailty are additional important risk factors for low BMD and fractures. Heightened fracture risk in RA may be mitigated by tight disease control, and biologic therapies are associated with more stable BMD compared to nonbiologic therapies. Evidence-based guidelines specific for treating osteoporosis in patients with RA do not exist. Thus, treatment decisions are based on general osteoporosis guidelines, taking into account additional RA-specific risk factors.
Recent studies have advanced knowledge of RA-specific risk factors for BMD loss and fractures. Future studies applying these findings to modify established fracture risk algorithms as well as evaluating osteoporosis treatments in RA cohorts are needed to reduce the risk of disabling fractures in these patients.
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.
Summary
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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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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