Fatty Acid Intake and Polyunsaturated Fatty Acid Biomarkers and Risk of Total Knee or Hip Arthroplasty Among Older Women in the Women's Health Initiative.

OBJECTIVE: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. METHODS: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. RESULTS: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. CONCLUSION: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

Prevalence and predictors of sustained remission/low disease activity after discontinuation of induction or maintenance treatment with tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic and scoping review.

BACKGROUND: To determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor inhibitors (TNFi), separately in induction treatment and maintenance treatment studies, and to identify predictors of successful discontinuation. METHODS: We performed a systematic literature review of studies published from 2005 to May 2022 that reported outcomes after TNFi discontinuation among patients in remission/LDA. We computed prevalences of successful discontinuation by induction or maintenance treatment, remission criterion, and follow-up time. We performed a scoping review of predictors of successful discontinuation. RESULTS: Twenty-two induction-withdrawal studies were identified. In pooled analyses, 58% (95% confidence interval (CI) 45, 70) had DAS28 < 3.2 (9 studies), 52% (95% CI 35, 69) had DAS28 < 2.6 (9 studies), and 40% (95% CI 18, 64) had SDAI ≤ 3.3 (4 studies) at 37-52 weeks after discontinuation. Among patients who continued TNFi, 62 to 85% maintained remission. Twenty-two studies of maintenance treatment discontinuation were also identified. At 37-52 weeks after TNFi discontinuation, 48% (95% CI 38, 59) had DAS28 < 3.2 (10 studies), and 47% (95% CI 33, 62) had DAS28 < 2.6 (6 studies). Heterogeneity among studies was high. Data on predictors in induction-withdrawal studies were limited. In both treatment scenarios, longer duration of RA was most consistently associated with less successful discontinuation. CONCLUSIONS: Approximately one-half of patients with RA remain in remission/LDA for up to 1 year after TNFi discontinuation, with slightly higher proportions in induction-withdrawal settings than with maintenance treatment discontinuation.

Health disparities in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation that involves symmetric polyarthritis of small and large joints. Autoimmune rheumatic diseases represent a significant socioeconomic burden as they are among the leading causes of death and morbidity due to increased risk of cardiovascular disease. Health disparities in patients with rheumatoid arthritis affect outcomes, prognosis, and management of the disease.

Racial disparities in immune-related adverse events of immune checkpoint inhibitors and association with survival based on clinical and biochemical responses.

BACKGROUND: Immune checkpoint inhibitors (ICPi) cause various immune-related adverse events (irAE) with thyroid dysfunction as a commonly reported abnormality. There is increasing evidence showing positive association with development of irAE and survival. However, prior trials with ICPi had underrepresentation of minorities with < 5% African Americans. AIM: To evaluate the association between development of irAE and survival outcomes among a racially diverse patient population. METHODS: Data on patients with stage IV solid malignancies treated with programmed cell death-protein 1/programmed death ligand 1 blockers between January 2013 and December 2018 across MedStar Georgetown Cancer Institute facilities were retrospectively reviewed. Patients treated with cytotoxic T-lymphocyte-associated protein 4 inhibitors were excluded. Progression free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using Kaplan-Meier methods and Wilcoxon rank sum test for comparison. RESULTS: Out of 293 patients who met eligibility criteria, 91 pts (31%) had any grade irAE; most common AE were endocrine (40.7%) specifically TSH elevation, dermatological (23.1%) and rheumatologic (18.7%). Proportion of irAE was significantly higher in Caucasians vs African Americans (60.4% vs 30.8%), in patients with low programmed death ligand 1, lower LDH, older age, and those who had more treatment cycles with ICPi. Rate of progression was lower in patients with irAE (30.8% vs 46.0%, P = 0.0140). Median PFS (5.8 vs 3.0 mo, P = 0.0204) and OS (17.1 vs 7.2 mo, P < 0.0001) were higher with irAE. Statistically significant difference in OS (17.1 vs 8.6 mo, P = 0.0002) but not in PFS (5.8 vs 3.3 mo, P = 0.0545) was noted with endocrine irAE. No differences in survival were observed among other commonly reported irAE. Differences in survival among subgroups of patients with irAE are described. CONCLUSION: Development of irAE positively correlated with improved PFS and OS as reported in previous studies. To our knowledge, this is the first study observing differences in OS favoring endocrine AE and Caucasian race. These factors may be potential surrogate markers of prognosis pending replication of these results in large-scale studies.

Clinical and Imaging Response to Tumor Necrosis Factor Alpha Inhibitors in Treatment of Cardiac Sarcoidosis: A Multicenter Experience.

BACKGROUND: Cardiac sarcoidosis (CS) is an increasingly recognized cause of cardiomyopathy; however, data on immunosuppressive strategies are limited. Treatment with tumor necrosis factor (TNF) alpha inhibitors is not well described; moreover, there may be heart failure-related safety concerns. METHODS: Retrospective multicenter study of patients with CS treated with TNF alpha inhibitors. Baseline characteristics, treatments, and outcomes were adjudicated. RESULTS: Thirty-eight patients with CS (mean age 49.9 years, 42% women, 53% African American) were treated with TNF alpha inhibitor (30 infliximab, 8 adalimumab). Prednisone dose decreased from time of TNF alpha inhibitor initiation (21.7 ± 17.5 mg) to 6 months (10.4 ± 6.1 mg, P = .001) and 12 months (7.3 ± 7.3 mg, P = .002) after treatment. On pre-TNF alpha inhibitor treatment positron emission tomography with 18-flourodoxyglucose (FDG-PET), 84% of patients had cardiac FDG uptake. After treatment, there was a significant decrease in number of segments involved (3.5 ± 3.8 to 1.0 ± 2.5, P = .008) and maximum standardized uptake value (3.59 ± 3.70 to 0.57 ± 1.60, P = .0005), with 73% of patients demonstrating complete resolution or improvement of cardiac FDG uptake. The left ventricular ejection fraction remained stable (45.0 ± 16.5% to 47.0 ± 15.0%, P = .10). Four patients required inpatient heart failure treatment, and 8 had infections; 2 required treatment cessation. CONCLUSIONS: TNF alpha inhibitor treatment guided by FDG-PET imaging may minimize corticosteroid use and effectively reduce cardiac inflammation without significant adverse effect on cardiac function. However, infections were common, some of which were serious, and therefore patients require close monitoring for both infection and cardiac symptoms.

Coffee and Tea Consumption in Relation to Risk of Rheumatoid Arthritis in the Women's Health Initiative Observational Cohort.

OBJECTIVE: The aim of this study was to evaluate whether tea or coffee consumption is associated with an increased risk of older-onset rheumatoid arthritis (RA) using the Women's Health Initiative Observational Study. METHODS: The Women's Health Initiative Observational Study is a longitudinal prospective cohort study conducted from 1993 to 1998. There were 76,853 women who completed a self-administered questionnaire about their daily consumption of tea and coffee. One hundred eighty-five women self-reported and validated incident cases of RA were observed after 3 years of observation. Multivariable Cox proportional hazards models were performed to assess the relationship between consumption habits and disease incidence. Trend tests were calculated using categorical variables modeled as a continuous variable without collapsing. RESULTS: There was no increase in the hazard ratio for incident RA in those participants who drank coffee compared with those who did not. The amount of coffee consumed and the method of preparation (caffeinated/decaffeinated; filtered/unfiltered) also did not alter the risk of incident RA. There was a positive association of incident RA and caffeinated tea consumption in the trend test (p = 0.03). When assessing any caffeinated tea consumption versus no tea consumption, the hazard ratio for incident RA was 1.40 (confidence interval, 1.01-1.93; p = 0.04). CONCLUSIONS: In a large prospective cohort of older women, there was no association between coffee consumption and incident RA. A small association between daily caffeinated, nonherbal tea consumption and incident RA was found.

A Review of Osteoporosis in the Older Adult: An Update.

Osteoporosis in the elderly population is common. It results in more than 1.5 million fractures per year in the United States. The goal of managing osteoporosis is to prevent fractures. In men, osteoporosis is underrecognized and undertreated. More men than women die every year as a consequence of hip fractures. Bisphosphonates are the first-line treatment of men and women. In the past several years, advances in bone biology have resulted in major therapeutic advances. A review of diagnosis and treatment of osteoporosis is described.

Baricitinib, a Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials.

Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA. Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety of baricitinib in RA. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through 09/24/17 with restriction to English language. We excluded meeting abstracts without full text publication. We used RevMan 5.3 to perform meta-analysis between groups on baricitinib (2 and 4 mg daily) and placebo using random effect model calculating odds ratio (OR) as well as 95% confidence interval (CI). Compared to placebo, 2 mg of baricitinib was more effective in achieving ACR20 [54 vs. 36.6%; OR 2.09; 95% CI 1.60-2.71; p < 0.00001; I2 0%], ACR50 [31.6 vs. 10.3%; OR 2.3; 95% CI 1.68-3.15; p < 0.00001; I2 0%], and ACR70 responses [18.7 vs. 5.1%; OR 4.05; 95% CI 2.54-6.44; p < 0.00001; I2 0%]. Similarly, 4 mg of baricitinib daily was more effective than placebo. Baricitinib 2 mg once daily did not increase any adverse events [65.3 vs. 62.4%; OR 1.03; 95% CI 0.80-1.34; p = 0.8; I2 0%], serious adverse events [3.5 vs. 5%; OR 0.68; 95% CI 0.37-1.27; p = 0.22; I2 0%], and herpes zoster [1.2 vs. 0.4%; OR 2.34; 95% CI 0.27-20.47; p = 0.44; I2 37%] as compared to placebo. Similarly, 4 mg of baricitinib did not increase the risk of serious adverse events but increased herpes zoster infection [OR 3.88; 95% CI 1.36-11.06; p = 0.01; I2 0%] when compared to placebo. Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment.

A Review of Osteoporosis in the Older Adult.

Osteoporosis in the elderly population is common. It results in more than 1.5 million fractures per year in the United States. The goal of managing osteoporosis is to prevent fractures. In men, osteoporosis is underrecognized and undertreated. More men than women die every year as a consequence of hip fractures. A review of diagnosis and treatment of osteoporosis is described in this article. Bisphosphonates are the first-line treatment for men and women. In the past several years, advances in bone biology have resulted in major therapeutic advances.

A case of central nervous system nocardiosis in a patient with lupus treated with belimumab.

Belimumab was approved by the United States Food and Drug Administration in March 2011 as the first biological agent for treating active systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first case report regarding a patient with SLE treated with belimumab who was diagnosed with central nervous system nocardiosis.

Psoriasis and psoriatic arthritis in African-American patients--the need to measure disease burden.

Gaps in knowledge exist regarding the clinical characteristics of psoriatic disease in ethnic minority patients. We evaluated validated clinical disease measures of psoriasis and psoriatic arthritis in African-American and Caucasian patients. Adult outpatients with confirmed diagnoses of psoriasis and psoriatic arthritis and seen at four urban academic institutions were eligible for evaluation. Validated patient and physician-reported disease outcome parameters, quality of life measures of psoriasis and psoriatic arthritis, and frequencies of systemic immunosuppressive therapies and patient comorbidities were documented. Psoriatic arthritis was less frequent in African-Americans compared to Caucasians (30 vs. 64.5 %, respectively, p < 0.001); however, African-Americans had more severe skin involvement [Psoriasis Area and Severity Index 8.4 (10.0) vs. Caucasians 5.5 (6.4), p = 0.06], with greater psychological impact and impaired quality of life. Use of biologic therapies was greater in Caucasian patients (46.2 vs. 13.3 % in African-Americans, p < 0.0001); yet, only one in four patients of the study cohort achieved minimal disease activity. Comorbidity was not associated with frequency of immunosuppressive drug use. In order to achieve a target of low disease activity and to reduce ethnic disparities in the care of psoriatic disease, the routine application of measures of disease status is needed.

Understanding why rheumatoid arthritis patient treatment preferences differ by race.

OBJECTIVE: Rheumatoid arthritis (RA) patient preferences may account for some of the variability in treatment between racial groups. How and why treatment preferences differ by race is not well understood. We sought to determine whether African American and white RA patients differ in how they evaluate the specific risks and benefits related to medications. METHODS: A total of 136 RA patients completed a conjoint analysis interactive computer survey to determine how they valued the specific risks and benefits related to treatment characteristics. The importance that respondents assigned to each characteristic and the ratio of the importance that patients attached to overall benefit versus overall risk were calculated. Subjects having a risk ratio <1 were classified as being risk averse. RESULTS: The mean age of the study sample was 55 years (range 22-84). Forty-nine percent were African American and 51% were white. African American subjects assigned the greatest importance to the theoretical risk of cancer, whereas white subjects were most concerned with the likelihood of remission and halting radiographic progression. Fifty-two percent of African American subjects were found to be risk averse compared with 12% of the white subjects (P < 0.0001). Race remained strongly associated with risk aversion (adjusted odds ratio [95% confidence interval] 8.4 [3.1, -23.1]) after adjusting for relevant covariates. CONCLUSION: African American patients attach greater importance to the risks of toxicity and less importance to the likelihood of benefit than their white counterparts. Effective risk communication and improved understanding of expected benefits may help decrease unwanted variability in health care.

Racial disparities in treatment preferences for rheumatoid arthritis.

BACKGROUND: Data suggest that differences in patient preferences may account for racial disparities in the use of medical interventions. Racial disparities have also been noted in outcomes and the delivery of healthcare services in chronic disease. Whether treatment preferences in chronic disease differ by race is not known. METHODS: We elicited treatment preferences for aggressive therapy in patients with rheumatoid arthritis who identified themselves as being black or white. RESULTS: One hundred fifty consecutive eligible patients were invited to participate. Of these, 136 subjects completed the interview. In unadjusted analysis, 51% of white participants preferred aggressive therapy compared with 16% of blacks (P < 0.0001). Subjects who were married and reported having at least some college education had stronger preferences for aggressive therapy compared with their respective counterparts. After adjusting for covariates, race remained the strongest predictor of aggressive therapy examined in this study [adjusted odds ratio (95% confidence interval) = 11.2 (1.9-64.9)]. CONCLUSIONS: In this study, fewer black patients preferred aggressive treatment compared with white patients with similar disease severity. These results have important clinical implications because use of aggressive treatment improves both short- and long-term outcomes in rheumatoid arthritis. Efforts to improve patient education and physician communication should be made to ensure that all patients have an accurate understanding of the benefits, as well as risks, associated with the best available treatment options.

Validation of self-report of rheumatoid arthritis and systemic lupus erythematosus: The Women's Health Initiative.

OBJECTIVE: The Women's Health Initiative (WHI), initiated in 1993, enrolled 161,808 postmenopausal women aged 50-79 years and followed them with annual questionnaires for 8 years in order to study major causes of morbidity and mortality. Our objective was to determine the most effective and efficient means to validate self-reported rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in the WHI. METHODS: Data from 2 of 40 WHI clinical centers were used. Of these 7443 women, 643 self-reported RA and 106 self-reported SLE. Research coordinators contacted these women using mailers and telephone calls to obtain medical record releases and a Connective Tissue Screening Questionnaire (CSQ). Medical records were obtained on 286 self-reported RA and 34 self-reported SLE and reviewed by 3 rheumatologists blind to the self-reported diagnoses. Sensitivity, specificity, and the kappa statistic were computed to evaluate the level of agreement between self-report and chart review. RESULTS: Self-reported RA was accurate only 14.7% (42/286 cases) of the time. Coupling the self-report to medication data improved the positive predictive value (PPV; 62.2%) and kappa (0.53), suggesting a moderate agreement to chart review. Self-reported SLE was accurate only 11.8% (4/34 cases) of the time. Coupling the self-report to medication data improved the PPV (40.0%) and kappa (0.44), suggesting a moderate agreement to chart review. The CSQ was inferior to using medication data but was substantially better than self-report alone. CONCLUSION: The performance of disease self-report coupled with medication history in validating RA and SLE was very good and should obviate the need for time-consuming medical record reviews.

Women's preferences for prevention of bone loss.

OBJECTIVE: Despite the serious consequences of osteoporosis, few women use pharmacologic measures to prevent postmenopausal bone loss. We used an interactive computerized questionnaire to examine women's preferences for prevention of osteoporosis. METHODS: We administered a choice-based conjoint analysis survey (CBCA) to consecutive early postmenopausal women in a shopping center. The questionnaire was constructed to measure preferences for pharmacologic and nonpharmacologic measures to prevent postmenopausal bone loss. Women were also given the option of choosing "none," i.e., to defer or refuse all options. Utilities were calculated based on a Hierarchical Bayes model using Monte Carlo-Markov chain algorithms. We performed simulations based on women's values for specific treatment characteristics to estimate choice. RESULTS: A total of 212 women agreed to complete the survey (42% participation rate). Between 18% and 47% of the women surveyed (mean age 52+/-5 yrs) were predicted to choose once-weekly medications to prevent postmenopausal bone loss, assuming treatment confers an absolute lifetime risk reduction in fractures of at least 10%. CONCLUSION: In this CBCA survey, which derived preferences based on how women make tradeoffs between specific treatment characteristics, a significant percentage of women were willing to use once-weekly medications to prevent postmenopausal bone loss.