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.
Ultrasound evaluation of the Achilles tendon has been utilised to assess involvement at the entheses in the setting of various inflammatory, metabolic, and mechanical processes. The purpose of this ...systematic review was to evaluate the differences in ultrasound findings at the Achilles enthesis between inflammatory tendinopathy (IT) versus non-inflammatory tendinopathy (NIT).
A review of all studies involving ultrasound evaluation of IT or NIT (mechanical or metabolic) affecting the Achilles enthesis was performed by searching the Embase, PubMed and Medline databases from start until October 2020. We assessed study quality and extracted summary data from each individual study. We used random-effects meta-analysis to determine the average proportion of affected anatomic sites across all studies for each abnormality, weighting the analysis based on the size of each individual study.
Achilles enthesis thickening was more frequent in the symptomatic IT (sIT) group (37.8%) compared to the unspecified IT (25%), NIT (11.2%) and healthy control (2.7%) groups. Increased vascularity at the enthesis was more common in the NIT (23.4%) group compared to the IT (9%), sIT (8.6%) and healthy control (0.1%) groups. Erosions were more common among the IT (17.3%) and sIT (14%) groups compared to the NIT (2.2%) and healthy controls (0.3%) groups.
While Achilles enthesis thickening, Doppler signal and calcaneal erosions discriminate IT from healthy subjects, erosions are more likely to distinguish IT from NIT than thickening or Doppler signal. Additional study is needed to quantify the diagnostic performance of ultrasound at this location given the frequency of abnormalities in NIT.
Objective
Rheumatoid arthritis (RA) is associated with low muscle density due to the accumulation of intramuscular fat. The present study was undertaken to identify predictors of changes in muscle ...density and to determine whether low muscle density predicted changes in strength and physical function.
Methods
Patients with RA, ages 18–70 years, completed whole‐body dual‐energy x‐ray absorptiometry and peripheral quantitative computed tomography to quantify lean and fat mass indices and muscle density. Dynamometry was used to measure strength at the hand, knee, and lower leg. Disability and physical function were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Assessments were performed at baseline and at follow‐up. Regression analyses assessed associations between patient characteristics, muscle density, and deteriorations in strength and function.
Results
Muscle density was assessed at baseline in 107 patients with RA. Seventy‐nine of these patients (74%) returned for a follow‐up assessment at a median follow‐up time of 2.71 years (interquartile range 2.35–3.57). Factors associated with declines in muscle density included female sex, higher disease activity, smoking, and lower insulin‐like growth factor 1 (IGF‐1) levels. Greater muscle density Z score at baseline (per 1 SD) was associated with less worsening per year according to HAQ, SPPB, and 4‐meter walk time scores and a lower risk of a clinically important worsening in HAQ score (odds ratio OR 1.90 95% confidence interval (95% CI) 1.06, 3.42; P = 0.03) and walking speed (OR 2.87 95% CI 1.05, 7.89; P = 0.04).
Conclusion
Worsening of skeletal muscle density occurred in patients with higher disease activity, in smokers, and in those with lower IGF‐1. Low muscle density was associated with worsening of physical function. Interventions addressing reductions in muscle quality might prevent functional decline.
This study evaluated associations between fibroblast growth factor (FGF)-21, an adipokine associated with metabolic stress, and adverse longitudinal changes in body composition and physical ...functioning in patients with rheumatoid arthritis (RA).
At baseline and follow-up, patients with RA aged 18-70 years completed whole-body dual-energy X-ray absorptiometry and peripheral quantitative computed tomography to quantify lean mass, fat mass, and muscle density. Dynamometry assessed muscle strength at the hand and knee, and physical functioning was measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). FGF-21 and inflammatory cytokines were measured at baseline. Linear and logistic regression analyses assessed associations between FGF-21 levels and both body composition and physical functioning over time.
There were 113 patients with RA enrolled, and 84 (74%) returned for follow-up at a median of 2.68 years. At baseline, FGF-21 was associated with age, smoking, methotrexate use, adiposity, and inflammatory cytokines: tumor necrosis factor receptor type I, YKL-40, vascular endothelial growth factor (VEGF), and resistin. The highest FGF-21 quartile was associated with worse SPPB and HAQ. Higher baseline FGF-21 levels (per 1 SD) were associated with worsening in muscle density and area Z-scores (β -0.06, 95% CI -0.12 to 0.008,
= 0.08; and β -0.05, 95% CI -0.10 to 0.006,
= 0.08, respectively) and a greater probability of a clinically meaningful worsening of HAQ (OR 2.37, 95% CI 1.21-4.64,
= 0.01). The fourth FGF-21 quartile was associated with worsening of SPPB (β -0.57, 95% CI -1.04 to -0.09,
= 0.02).
FGF-21 levels are associated with obesity and inflammatory cytokines, and with worsening in physical functioning in RA. These data support the hypothesis that FGF-21 can identify patients at risk of functional decline.
To determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD.
We studied US veterans with RA-ILD participating in a multicentre, ...prospective RA cohort study. RA disease activity (28-joint DAS DAS28-ESR) and functional status (multidimensional HAQ MDHAQ) were collected longitudinally while pulmonary function tests (forced vital capacity FVC, diffusing capacity for carbon monoxide) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden and medications.
We followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio aHR 1.21; 95% CI: 1.03, 1.41) and MDHAQ (aHR 1.85; 95% CI: 1.29, 2.65) were separately associated with mortality independent of FVC and other confounders. Modelled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment (<80% predicted) was significantly associated with mortality risk. Those with a combination of moderate/high disease activity and FVC <80% predicted had the highest risk of death (aHR 4.43; 95% CI: 1.70, 11.55).
Both RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.
Background
Conventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to ...determine the associations of sarcopenia and relative sarcopenia with mortality independent of co‐morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations.
Methods
Dual energy X‐ray absorptiometry‐derived appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2) were assessed in 14 850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow‐up through 2011. Sarcopenia was defined using sex‐specific and race/ethnicity‐specific standard deviation scores compared with young adults (T‐scores) as an ALMI T‐score < −2 and relative sarcopenia as fat‐adjusted ALMI (ALMIFMI) T‐score < −2. Glomerular filtration rate (GFR) was estimated using creatinine‐based (eGFRCr) and cystatin C‐based (eGFRCys) regression equations.
Results
Three (3.0) per cent of National Health and Nutrition Examination Survey participants met criteria for sarcopenia and 8.7% met criteria for relative sarcopenia. Sarcopenia and relative sarcopenia were independently associated with mortality (HR sarcopenia 2.20, 95% CI 1.69 to 2.86; HR relative sarcopenia 1.60, 95% CI 1.31 to 1.96). The corresponding population attributable risks were 5.2% (95% CI 3.4% to 6.4%) and 8.4% (95% CI 4.8% to 11.2%), respectively. Relative sarcopenia remained significantly associated with mortality (HR 1.32, 95% CI 1.08 to 1.61) when limited to the subset who did not meet the criteria for sarcopenia. The risk of mortality associated with relative sarcopenia was attenuated among persons with higher FMI (P for interaction <0.01) and was not affected by CKD status for either sarcopenia or relative sarcopenia.
Conclusions
Sarcopenia and relative sarcopenia are significantly associated with mortality regardless of CKD status. Relative sarcopenia is nearly three‐fold more prevalent amplifying its associated mortality risk at the population level. The association between relative sarcopenia and mortality is attenuated in persons with higher FMI.
Patients with rheumatoid arthritis (RA) are at increased risk for infection after arthroplasty, yet risks of specific biologic medications are unknown.
To compare risk for postoperative infection ...among biologics and to evaluate the risk associated with glucocorticoids.
Retrospective cohort study.
Medicare and Truven MarketScan administrative data from January 2006 through September 2015.
Adults with RA who were having elective inpatient total knee or hip arthroplasty, either primary or revision, and had a recent infusion of or prescription for abatacept, adalimumab, etanercept, infliximab, rituximab, or tocilizumab before surgery.
Propensity-adjusted analyses using inverse probability weights evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non-urinary tract hospitalized infections and 30-day readmissions.
Among 9911 patients treated with biologics, 10 923 surgical procedures were identified. Outcomes were similar in patients who received different biologics. Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk from propensity-weighted models ranged from 6.87% (95% CI, 5.30% to 8.90%) with adalimumab to 8.90% (CI, 5.70% to 13.52%) with rituximab. Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (CI, 0.11% to 1.12%) with rituximab to 3.67% (CI, 1.69% to 7.88%) with tocilizumab. Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes. Propensity-weighted models showed that use of more than 10 mg of glucocorticoids per day (vs. no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (CI, 9.72% to 17.81%) (vs. 6.78%) and a predicted 1-year cumulative incidence of PJI of 3.83% (CI, 2.13% to 6.87%) (vs. 2.09%).
Residual confounding is possible, and sample sizes for rituximab and tocilizumab were small.
Risks for hospitalized infection, PJI, and readmission after arthroplasty were similar across biologics. In contrast, glucocorticoid use, especially with dosages above 10 mg/d, was associated with greater risk for adverse outcomes.
Rheumatology Research Foundation, National Institutes of Health, and Bristol-Myers Squibb.
Objective
We aimed to determine if there were sex differences in lean body mass (LBM) in patients with rheumatoid arthritis (RA) when compared with sex‐ and race‐specific National Health and ...Nutrition Examination Survey (NHANES) reference data, and to investigate the impact of sex differences in risk factors for LBM deficits.
Methods
Dual x‐ray absorptiometry measures of whole body LBM and appendicular LBM (arms and legs, appendicular lean mass ALM) were obtained on a total of 190 subjects from 2 independent cohorts (141 from San Francisco SF, 49 from Philadelphia PA), expressed as indices adjusted for height (LBM index and ALM index, kg/m2), and converted to sex‐ and race‐specific Z scores relative to age and based on NHANES data. Sarcopenia was defined using 4 different sex‐specific definitions. Multivariable linear and logistic regression analyses adjusted for disease activity, disease duration, physical activity, anti–cyclic citrullinated peptide seropositivity, fat mass index, and glucocorticoid use.
Results
While there were significant differences between the 2 cohorts, ALM index Z scores were significantly lower in men compared to women in both (SF: −1.43 versus −0.43, P < 0.0001; PA: −0.83 versus −0.06, P = 0.03). Observed sex differences were significant after adjustment in multivariable analyses within both cohorts. Odds of sarcopenia were 3 to 8 times greater in men in the SF cohort. Men in the PA cohort also had a higher, but nonsignificant, risk of sarcopenia.
Conclusion
RA is associated with significant LBM deficits, with greater deficits observed in men. Future study may help elucidate the mechanisms driving greater deficits among men.
The study was to determine the prevalence of baseline risk factors for cardiovascular outcomes and cancer among commercially-insured patients with rheumatoid arthritis (RA) during their first ...dispensed treatment for either tumor necrosis factor inhibitors (TNFi) or JAK inhibitors (JAKi).
Patients with RA from August 16, 2019 to March 31, 2022 were identified in the Merative MarketScan Commercial and Medicare databases. The first date that a TNFi or JAKi was dispensed was the index date, and baseline risk factors were assessed among patients continuously eligible for 12 months before the index date. Patients who had the following were stratified into an elevated risk category: age ≥65 years, smoking, or a history of a major adverse cardiovascular event, venous thromboembolism, or cancer. The prevalence of modifiable risk factors was also reported: hypertension, hyperlipidemia, obesity, and diabetes. The crude prevalence and prevalence difference (PD) were reported.
A total of 12,673 patients (TNFi n = 7,748; 61% and JAKi n = 4,925; 39%) met inclusion criteria. The prevalence of elevated risk was the same for all patients using TNFi (n = 2,051; 26%) and JAKi (n = 1,262; 26%). Compared with patients having low risk, patients with an elevated risk also had a higher prevalence of at least one primary modifiable risk factor for both patients using JAKi (79% vs 58%; PD 21%, 95% confidence interval CI 18%-24%) and TNFi (81% vs 60%; PD 21%, 95% CI 19%-23%).
In recent years, JAKi and TNFi were used in similar proportions to treat RA among commercially-insured patients at elevated cardiovascular and cancer risk. Because uncontrolled disease, modifiable comorbidities, and treatment with JAKi are associated with these adverse events, future studies evaluating how practice patterns may be affected by the emergence of safety data will be of value.
To update and validate the Rheumatic Disease Comorbidity Index (RDCI) utilizing International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes.
We defined ICD-9-CM ...(n = 1,068) and ICD-10-CM (n = 1,425) era cohorts (n = 862 in both) spanning the ICD-9-CM to ICD-10-CM transition in a multicenter, prospective rheumatoid arthritis registry. Information regarding comorbidities was collected from linked administrative data over 2-year assessment periods. An ICD-10-CM code list was generated from crosswalks and clinical expertise. ICD-9- and ICD-10-derived RDCI scores were compared using intraclass correlation coefficients (ICC). The predictive ability of the RDCI for functional status and death during follow-up was assessed using multivariable regression models and goodness-of-fit statistics (Akaike's information criterion AIC and quasi information criterion QIC) in both cohorts.
Mean ± SD RDCI scores were 2.93 ± 1.72 in the ICD-9-CM cohort and 2.92 ± 1.74 in the ICD-10-CM cohort. RDCI scores had substantial agreement in individuals who were in both cohorts (ICC 0.71 95% confidence interval 0.68-0.74). Prevalence of comorbidities was similar between cohorts with absolute differences <6%. Higher RDCI scores were associated with a greater risk of death and poorer functional status during follow-up in both cohorts. Similarly, in both cohorts, models including the RDCI score had the lowest QIC (functional status) and AIC (death) values, indicating better model performance.
The newly proposed ICD-10-CM codes for the RDCI-generated comparable RDCI scores to those derived from ICD-9-CM codes and are highly predictive of functional status and death. The proposed ICD-10-CM codes for the RDCI can be used in rheumatic disease outcomes research spanning the ICD-10-CM era.
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