Objective

Citrullinated proteins have been found within atherosclerotic plaque. However, studies evaluating the association between anti-citrullinated protein antibodies (ACPAs) and imaging measures of atherosclerosis in patients with rheumatoid arthritis (RA) have been limited to seroreactive citrullinated fibrinogen or citrullinated vimentin and have rendered contradictory results. Therefore, our objective was to evaluate this association using an extended panel of ACPAs in a larger sample of RA patients without clinical cardiovascular disease (CVD).

Methods

ACPAs were identified using a custom Bio-Plex bead assay in 270 patients from 2 independent RA cohorts without clinical CVD, with the first one consisting of 195 patients and the other of 75 patients. Coronary artery calcium (CAC) was assessed by computed tomography as a measure of coronary artery disease.

Results

High levels of anti-citrullinated histone H2B antibodies were strongly associated with higher CAC scores, compared with lower antibody levels (P = 0.001); this remained significant after adjustment for traditional CV and RA-specific risk factors (P = 0.03). No association between levels of ACPAs and CAC progression at 3 years was seen (P = 0.09); however, the number of progressors was small (n = 92).

Conclusion

Higher levels of ACPAs targeting Cit-histone H2B were associated with higher CAC scores when compared to lower antibody levels, suggesting a potential role for histone citrullination seroreactivity in atherosclerosis.

Objective

Systemic inflammation and insulin resistance (IR) are linked, yet the determinants of IR and its impact on atherosclerosis in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and non-RA populations and investigate whether the associations of IR with measures of atherosclerosis differ between these groups.

Methods

IR was quantified using the homeostatic model assessment of IR (HOMA-IR), and was compared between RA patients and demographically matched non-RA controls. Differences in the associations between the HOMA-IR index and the Agatston coronary artery calcium (CAC) score, ultrasound-determined intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA), and focal plaque in the ICA/carotid bulb were compared according to RA status.

Results

Among the 195 RA patients and 198 controls studied, average HOMA-IR levels were higher in the RA group by 31%, and were consistently higher in the RA group regardless of stratification by demographic or cardiometabolic risk factors. While the HOMA-IR index was strongly and significantly associated with C-reactive protein (CRP) and interleukin-6 (IL-6) levels in the control group, the association was weaker in the RA group. Among RA patients, higher HOMA-IR levels were associated with rheumatoid factor (RF) seropositivity in men and women, and prednisone use in women only. Before adjustment, higher HOMA-IR levels were associated with all assessed measures of subclinical atherosclerosis in the control group only; associations were diminished and lost statistical significance after adjustment for cardiovascular risk factors. Among the RA patients, neither baseline nor average HOMA-IR levels were significantly associated with change in any of the atherosclerosis measures over an average of 3.2 years of followup.

Conclusion

Although IR was higher in RA patients than in non-RA controls, higher levels may not independently impart additional risk of atherosclerosis.

Introduction

In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown.

Methods

Incidence and progression of CAC were compared in 155 patients with RA and 835 control participants. The association of demographic characteristics, traditional cardiovascular risk factors, RA disease characteristics and selected inflammatory markers with incidence and progression of CAC were evaluated.

Results

The incidence rate of newly detected CAC was 8.2/100 person-years in RA and 7.3/100 person-years in non-RA control subjects [IRR 1.1 (0.7-1.8)]. RA patients who developed newly detectable CAC were older (59 ± 7 vs. 55 ± 6 years old, p=0.03), had higher triglyceride levels (137 ± 86 vs. 97 ± 60 mg/dL, p=0.03), and higher systolic blood pressure (129 ± 17 vs. 117 ± 15 mm Hg, p=0.01) compared to those who did not develop incident CAC. Differences in blood pressure and triglyceride levels remained significant after adjustment for age (p<=0.05). RA patients with any CAC at baseline had a median rate of yearly progression of 21 (7-62) compared to 21 (5-70) Agatston units in controls. No statistical differences between RA progressors and RA non-progressors were observed for inflammatory markers or for RA disease characteristics.

Conclusions

The incidence and progression of CAC did not differ between RA and non-RA participants. In patients with RA, incident CAC was associated with older age, higher triglyceride levels, and higher blood pressure, but not with inflammatory markers or RA disease characteristics.

Objective

Little is known about early knee osteoarthritis (OA). The significance of lesions on magnetic resonance imaging (MRI) in older persons without radiographic OA is unclear. Our objectives were to determine the extent of tissue pathology by MRI and evaluate its significance by testing the following hypotheses: cartilage damage, bone marrow lesions, and meniscal damage are associated with prevalent frequent knee symptoms and incident persistent symptoms; bone marrow lesions and meniscal damage are associated with incident tibiofemoral (TF) cartilage damage; and bone marrow lesions are associated with incident patellofemoral (PF) cartilage damage.

Methods

In a cohort study of 849 Osteoarthritis Initiative (OAI) participants who had a bilateral Kellgren/Lawrence (K/L) score of 0, we assessed cartilage damage, bone marrow lesions, and meniscal damage using the MRI OA Knee Score, as well as prevalent frequent knee symptoms, incident persistent symptoms, and incident cartilage damage. Multiple logistic regression (one knee per person) was used to evaluate associations between MRI lesions and each of these outcomes.

Results

Of the participants evaluated, 76% had cartilage damage, 61% had bone marrow lesions, 21% had meniscal tears, and 14% had meniscal extrusion. Cartilage damage (any; TF and PF), bone marrow lesions (any; TF and PF), meniscal extrusion, and body mass index (BMI) were associated with prevalent frequent symptoms. Cartilage damage (isolated PF; TF and PF), bone marrow lesions (any; isolated PF; TF and PF), meniscal tears, and BMI were associated with incident persistent symptoms. Hand OA, but no individual lesion type, was associated with incident TF cartilage damage, and bone marrow lesions (any; any PF) with incident PF damage. Having more lesion types was associated with a greater risk of outcomes.

Conclusion

MRI-detected lesions are not incidental and may represent early disease in persons at increased risk of knee OA.

Objective

To investigate the public health impact of obesity and other modifiable risk factors related to physical inactivity in adults with knee osteoarthritis (OA).

Methods

The frequency of inactivity as defined by the US Department of Health and Human Services was assessed from objective accelerometer monitoring of 1,089 participants (ages 49-84 years) with radiographic knee OA during the Osteoarthritis Initiative 48-month visit (2008-2010). The relationship between modifiable factors (weight status, dietary fat, fiber, smoking, depressive symptoms, knee function, knee pain, and knee confidence) with inactivity was assessed using odds ratios (ORs) and attributable fractions (AFs), controlling for descriptive factors (age, sex, race, education, lives alone, employment, frequent knee symptoms, and comorbidity).

Results

Almost half (48.9%) of participants with knee OA were inactive. Being overweight (OR 1.8, 95% confidence interval [95% CI] 1.2-2.5) or obese (OR 3.9, 95% CI 2.6-5.7), having inadequate dietary fiber intake (OR 1.6, 95% CI 1.2-2.2), severe knee dysfunction (OR 1.9, 95% CI 1.3-2.8), and severe pain (OR 1.7, 95% CI 1.1-2.5) were significantly related to inactivity, controlling for descriptive factors. Modifiable factors with significant average AFs were being overweight or obese (AF 23.8%, 95% CI 10.5-38.6%) and inadequate dietary fiber (AF 12.1%, 95% CI 0.1-24.5%), controlling for all factors.

Conclusion

Being obese or overweight, the quality of the diet, severe pain, and severe dysfunction are significantly associated with physical inactivity in adults with knee OA. All components should be considered in designing physical activity interventions that target arthritis populations with low activity levels.

Abstract Introduction In cross-sectional studies, patients with rheumatoid arthritis (RA) have higher coronary artery calcium (CAC) than controls. However, their rate of progression of CAC and the predictors of CAC progression have heretofore remained unknown. Methods Incidence and progression of CAC were compared in 155 patients with RA and 835 control participants. The association of demographic characteristics, traditional cardiovascular risk factors, RA disease characteristics and selected inflammatory markers with incidence and progression of CAC were evaluated. Results The incidence rate of newly detected CAC was 8.2/100 person-years in RA and 7.3/100 person-years in non-RA control subjects [IRR 1.1 (0.7-1.8)]. RA patients who developed newly detectable CAC were older (59±7 vs. 55±6 years old, p=0.03), had higher triglyceride levels (137±86 vs. 97±60 mg/dL, p=0.03), and higher systolic blood pressure (129±17 vs. 117±15 mm Hg, p=0.01) compared to those who did not develop incident CAC. Differences in blood pressure and triglyceride levels remained significant after adjustment for age (p<=0.05). RA patients with any CAC at baseline had a median rate of yearly progression of 21 (7–62) compared to 21 (5–70) Agatston units in controls. No statistical differences between RA progressors and RA non-progressors were observed for inflammatory markers or for RA disease characteristics. Conclusions The incidence and progression of CAC did not differ between RA and non-RA participants. In patients with RA, incident CAC was associated with older age, higher triglyceride levels, and higher blood pressure, but not with inflammatory markers or RA disease characteristics.

Objective

To evaluate the effect of sustained American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission on residual joint inflammation assessed by magnetic resonance imaging (MRI) and to secondarily evaluate other clinical definitions of remission, within an early seropositive rheumatoid arthritis (RA) cohort.

Methods

A subcohort of 118 RA patients was enrolled from patients who completed the 2-year, double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Patients received a single contrast-enhanced 1.5T MRI of their most involved wrist. Two readers scored MRIs for synovitis, osteitis, tenosynovitis, and erosions. Clinical assessments were performed every 3 months during the trial and at time of MRI.

Results

The subcohort was 92% seropositive with mean age 51 years, duration 4.1 months, and Disease Activity Score in 28 joints using the erythrocyte sedimentation rate 5.8 at TEAR entry. Total MRI inflammatory scores (tenosynovitis + synovitis + osteitis) were lower among patients in clinical remission. Lower MRI scores were correlated with longer duration of Clinical Disease Activity Index (CDAI) remission (ρ = 0.22, P = 0.03). At the time of MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients had MRI evidence of residual joint inflammation after 2 years. No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups.

Conclusion

This is the first detailed appraisal describing the relationship between clinical remission cut points and MRI inflammatory scores within an RA randomized controlled trial. The most stringent remission criteria (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores. These results document that 2 years of triple therapy or tumor necrosis factor plus methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation.

Objective

To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.

Methods

We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.

Results

The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).

Conclusion

This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

Objective

Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1.

Methods

A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year.

Results

At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year.

Conclusion

In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.