Arthritis Care & Research最新文献

Purpose: Frailty occurs prematurely in rheumatoid arthritis (RA) and is associated with poor health outcomes. We compared the performance of four frailty instruments, including a pragmatic alternative measure using chair sit-to-stand (STS), and evaluated their abilities to predict poor health outcomes.

Methods: Frailty was measured at baseline using four instruments: Fried Frailty Phenotype with STS (Fried-STS), Fried Frailty Phenotype with hand grip strength (Fried-HGS), VA-Frailty Index (VA-FI), and FRAIL Scale (FRAIL). Outcomes collected at 1-year follow-up included category of falls (none, 1, >1), category of days hospitalized (none, 1-3, >3), and a composite outcome of fall, hospitalization or death. Ordinal logistic or logistic regression models, adjusted for age and sex, explored the association of frailty and each outcome.

Results: 143 participants were included, aged 64.5±11.7 years, 73% male, and 69% White. Categorization as frail differed by instrument: Fried-STS (17%), Fried-HGS (15%), VA-FI (36%), and FRAIL (20%). There was poor agreement between frailty instruments (k=0.07-0.31) except for Fried-STS and Fried-HGS (k=0.62). Frailty by Fried-STS, Fried-HGS, and FRAIL were associated with falls (aORs: 3.83-9.54, p<0.05). Frailty by VA-FI was associated with days hospitalized (aOR: 5.21, p=0.017). Frailty by Fried-STS, VA-FI, and FRAIL were all associated with higher odds of the composite measure of incident fall, hospitalization, or death (aORs: 2.93-7.25, p<0.05).

Conclusion: Each frailty measure predicted adverse health outcomes, with phenotypic and patient-reported measures predicting falls while the deficit accumulation model predicted hospitalization days. Being frail by Fried-HGS did not predict poor outcomes as well as the other frailty instruments, including Fried-STS.

Objective: We assessed the effectiveness of PrismRA to improve clinical outcomes among patients with rheumatoid arthritis (RA) initiating treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD).

Methods: PrismRA incorporated 19 gene expression features and four clinical features to assess a patient's likelihood of inadequate response to tumor necrosis factor inhibitor (TNFi). PrismRA was assessed in a prospective, interventional cohort study of patients initiating treatment with a b/tsDMARD. PrismRA results were provided to treating rheumatologists and incorporated into the selection of TNFi vs non-TNFi for study treatment. External comparator patients were identified in a rheumatology provider electronic health records system and matched to PrismRA patients using propensity scores. All patients had moderate-high disease activity at baseline. The primary study outcome was achievement of minimal important difference (MID) in clinical disease activity index (CDAI) at 24 weeks. Last observation carried forward was used to impute missing data.

Results: There were 330 PrismRA cohort patients and 990 matched comparator patients. Key baseline patient characteristics were all well-balanced between cohorts. Study treatment selection was consistent with PrismRA results in 82% of PrismRA cohort patients. CDAI MID at 24 weeks was achieved by 63.0% of PrismRA patients and 42.4% of comparator patients (odds ratio 2.31, confidence interval 1.79-2.99).

Conclusion: PrismRA results informing selection of TNFi vs non-TNFi treatment was associated with better CDAI outcomes compared to matched external comparator patients. PrismRA testing helps fill the need for a precision medicine approach to more rapidly identify the most effective therapy for individual patients with RA.

Objective: Traumatic life events are hypothesized to be triggers for the onset of fibromyalgia. Posttraumatic stress disorder (PTSD) is a common comorbidity of fibromyalgia. However, limited prospective data are available on the development of fibromyalgia after exposure to high-magnitude stress.

Methods: This longitudinal cohort study of US military service members (N = 1,761) assessed fibromyalgia and PTSD before and upon return from combat deployment. Fibromyalgia was assessed with the 2011 questionnaire modification of the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia. The PTSD Checklist Stressor-Specific Version was used to assess symptoms of PTSD.

Results: The prevalence rates of fibromyalgia in service members at predeployment (men = 2.2%; women = 2.0%) were similar to rates in civilian populations. Following deployment, the prevalence of fibromyalgia increased significantly to 8.0% in men and 11.1% in women (P < 0.001). The prevalence of PTSD symptoms at predeployment was 20.7% in men and 18.3% in women. The prevalence post deployment increased slightly to 22.7% in men and 25.5% in women (P > 0.05). By odd ratios, service members with PTSD predeployment were 2.96 times more likely to develop fibromyalgia post deployment, and those with fibromyalgia predeployment were 3.12 times more likely to develop PTSD post deployment.

Conclusions: This study provides the largest prospective data to date to support exposure to the stress of deployment to a warzone as a significant factor related to the onset of fibromyalgia. The bidirectional comorbidity between fibromyalgia and PTSD suggests a potential link in the central nervous system and has implications for management.

Objective: Daily rhythms may be critical for maintaining homeostasis of joint tissues. We aimed to investigate the relationships between circadian clock disruption, sleep, and osteoarthritis (OA) risk in humans.

Methods: In the UK Biobank, a prospective 500,000-person cohort, we evaluated associations between sleep duration, sleeplessness/insomnia, and shift work type with four endpoints: knee OA, hip OA, total knee arthroplasty (TKA), and total hip arthroplasty. Cox regression was used to estimate associations with OA endpoints adjusting for age, sex, education, race, Townsend Deprivation Index, manual work frequency, and frequency of occupational walking/standing. Associations with and without adjustment for body mass index were estimated, as circadian clock disruption may influence OA through effects on obesity.

Results: For all OA endpoints, risk was highest among those getting <6 hours of nightly sleep (e.g. hazard ratio [HR]s for <6 vs. 7 hours: 1.21-1.41), and 'Usually' experiencing sleeplessness/insomnia compared to 'Never/Rarely' was associated with higher risk (HRs: 1.24-1.40). Night shift workers had 24% higher knee OA risk (HR=1.24 95%CI=1.12-1.38) and 28% higher TKA risk (HR=1.28 95%CI=1.19-1.37) compared to non-shift workers. After controlling for body mass index, associations were attenuated, but short sleep and sleeplessness/insomnia remained associated with all endpoints, and night shift work remained associated with knee OA and TKA. Sleep associations were similar after excluding participants reporting chronic knee/hip pain at sleep assessment.

Conclusions: Disruption of sleep or circadian rhythms may be modifiable risk factors for OA underlying cartilage degeneration through obesity and obesity-independent pathways. These findings point to potential ways to prevent OA.

Objective: Somatic items used in depression assessments can potentially overlap with symptoms related to physical illness, including systemic sclerosis (SSc). No studies have looked at whether somatic depression items may be influenced by diffuse versus limited SSc disease subtypes, which are associated with varying degrees of symptom presentation. The objective of this study was to evaluate differential item functioning (DIF) in items of the 8-item Patient Health Questionnaire (PHQ-8) across SSc subtypes. We also assessed the PHQ-8 for DIF across language (English and French), sex, and age.

Methods: Participants enrolled in the Scleroderma Patient-centered Intervention Network Cohort who completed the PHQ-8 at enrollment between April 2014 and October 2020 were included. Confirmatory factor analysis (CFA) was used to evaluate the unidimensional structure of the PHQ-8, and DIF analyses based on SSc subtype, language, sex, and age were conducted using Multiple Indicators Multiple Causes models.

Results: In total, 2,191 participants were included. CFA with several covarying error terms supported a one-factor structure for the PHQ-8 (Tucker Lewis Index = 0.99, Comparative Fit Index = 0.98, Root Mean Square Error of Approximation = 0.08). We did not identify statistically significant DIF based on SSc subtype. Statistically significant DIF was found in 1 item for language, 1 item for sex, and 2 items for age. However, the effect of DIF on overall PHQ-8 scores was negligeable in all cases.

Conclusion: We did not find evidence that the PHQ-8 performs differently across SSc subtypes, language of administration, sex, and age groups.

Objectives: The objective of this study was to investigate the association between dual seropositive, single seropositive and seronegative rheumatoid arthritis (RA) with radiographic erosions, disease flares, and mortality.

Methods: We performed a retrospective, population-based study of residents in southern Minnesota with incident RA who fulfilled criteria for RA in 2003-2019. Radiographic erosions and flares were evaluated within one year of incident RA. All-cause mortality was obtained from medical records and death certificates. Cox models adjusted for age, sex, smoking status, year of incident RA, and comorbidities were used.

Results: The study included 1,373 patients with RA. At RA incidence, 37% were dual seropositive, 13% seropositive for anti-CCP only, 12% seropositive for RF only, and 38% seronegative. The highest proportion of radiographic erosions prior to or within one year of RA incidence was in the dual seropositive (31%) and lowest in those seropositive for anti-CCP only (13%). Flares occurred in 69% of the dual seropositive and 51% of the seropositive for anti-CCP only within the first year of RA incidence. Those seropositive for RF only had over a two-fold increase in mortality compared to the seronegatives (adjusted Hazard Ratio [aHR]: 2.18 [95%CI:1.47-3.24]). In contrast, the dual seropositives had only a >50% increase in mortality (aHR: 1.66 [95%CI:1.21-2.28]) and those seropositive only for anti-CCP had a >30% increase in mortality (aHR: 1.32 [95%CI:0.83-2.11]).

Conclusion: RA patients seropositive for RF only have an increase in mortality compared to patients who are dual seronegative. RF positivity could be an indicator of inflammation that requires pharmacologic treatment to decrease mortality.

Objective: The objective of this study was to describe the longitudinal disease course and pulmonary outcomes of North American patients with melanoma differentiation-associated gene 5 antibody (MDA5 ab) associated dermatomyositis (DM).

Methods: Thirty patients with MDA5 ab DM were identified in a single center longitudinal cohort of 352 patients with idiopathic inflammatory myopathies. Longitudinal assessments of patient clinical and laboratory disease characteristics, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) chest scans were conducted.

Results: Eighty percent (n=24/30) of MDA5 ab DM patients had ILD. The overall mortality was low [2/24 at a follow-up of 4.0 ± 0.8 (mean±SD) years]. At this follow-up patients were receiving 3.1 ± 1.3 therapies, including 79% receiving IVIg, 58% rituximab, 67% mycophenolate, and 63% corticosteroids. In 18/22 surviving ILD patients who had 2-year longitudinal follow-up available at 1.8 ± 0.6 years, improvements of 16% and 17% in percent predicted (%pred) forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) were noted. In 10/18 patients with additional long-term follow-up available (6.8 ± 3.4 years), improvements of 24% and 20% pred FVC and DLCO were noted. Levels of MDA5 ab, IL-15 and paraoxonase 1 (PON1) enzyme activity correlated significantly with disease activity at baseline and longitudinally.

Conclusions: In a North American MDA5 ab DM-ILD cohort treated with aggressive combination immunomodulatory therapy including predominantly mycophenolate, IVIg, and rituximab, disease mortality was low and lung function improved markedly. IL-15, PON1, and MDA5 ab titers warrant further investigation as disease activity biomarkers in this high-risk population.