Antinuclear Matrix Protein 2 Autoantibodies and Edema,Muscle Disease,and Malignancy Risk in Dermatomyositis Patients

Objective

Dermatomyositis (DM ) patients typically present with proximal weakness and autoantibodies that are associated with distinct clinical phenotypes. We observed that DM patients with autoantibodies recognizing the nuclear matrix protein NXP ‐2 often presented with especially severe weakness. The aim of this study was to characterize the clinical features associated with anti–NXP ‐2 autoantibodies.

Methods

There were 235 DM patients who underwent testing for anti–NXP ‐2 autoantibodies. Patient characteristics, including muscle strength, were compared between those with and without these autoantibodies. The number of cancer cases observed in anti–NXP ‐2‐positive subjects was compared with the number expected in the general population.

Results

Of the DM patients, 56 (23.8%) were anti–NXP ‐2‐positive. There was no significant difference in the prevalence of proximal extremity weakness in patients with and without anti–NXP ‐2. In contrast, anti–NXP ‐2‐positive patients had more prevalent weakness in the distal arms (35% versus 20%; P = 0.02), distal legs (25% versus 8%; P < 0.001), and neck (48% versus 23%; P < 0.001). Anti–NXP ‐2‐positive subjects were also more likely to have dysphagia (62% versus 35%; P < 0.001), myalgia (46% versus 25%; P = 0.002), calcinosis (30% versus 17%; P = 0.02), and subcutaneous edema (36% versus 19%; P = 0.01) than anti–NXP ‐2‐negative patients. Five anti–NXP ‐2‐positive subjects (9%) had cancer‐associated myositis, representing a 3.68‐fold increased risk (95% confidence interval 1.2–8.6) compared to the expected prevalence in the general population.

Conclusion

In DM , anti–NXP ‐2 autoantibodies are associated with subcutaneous edema, calcinosis, and a muscle phenotype characterized by myalgia, proximal and distal weakness, and dysphagia. As anti–NXP ‐2‐positive patients have an increased risk of cancer, we suggest that they undergo comprehensive cancer screening.

     

Autoantibodies Targeting Ficolin‐2 in Systemic Lupus Erythematosus Patients With Active Nephritis

Objective

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterized by the production of various autoantibodies. The aim of this study was to investigate the presence of anti–ficolin‐2 antibodies in SLE patients and to evaluate the association between the levels of these autoantibodies, clinical manifestations, and disease activity.

Methods

This is a comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE patients were further divided into 2 groups (low disease activity [SLE Disease Activity Index (SLEDAI) score ≤4, n = 88] and high disease activity [SLEDAI score >4, n = 77]). Clinical manifestations were defined according to the physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy. Detection of anti–ficolin‐2 antibodies was performed by enzyme‐linked immunosorbent assay.

Results

Levels of anti–ficolin‐2 autoantibodies were significantly higher in SLE patients as compared to healthy subjects and associated with SLEDAI score. They were found to be positive in 61 of 165 SLE patients (37%). The presence of anti–ficolin‐2 antibodies was significantly related only to renal involvement, with a very high prevalence (86%) of anti–ficolin‐2 antibodies in SLE patients with active LN. Patients with active proliferative LN had significantly more positive anti–ficolin‐2 antibodies than those with nonproliferative LN. The combination of anti–ficolin‐2, anti–ficolin‐3, and anti‐C1q demonstrated a very high specificity (98%) for the diagnosis of active LN.

Conclusion

Our results support the usefulness of anti–ficolin‐2 as a complementary serologic biomarker for the diagnosis of active lupus with renal manifestations.

     

Association Between Anti–Citrullinated Fibrinogen Antibodies and Coronary Artery Disease in Rheumatoid Arthritis

Objective

Antibodies against citrullinated fibrinogen (anti–Cit‐fibrinogen) have been implicated in rheumatoid arthritis (RA) and associated with cardiovascular risk in RA. The objective of this study was to examine the association between anti–Cit‐fibrinogens and coronary artery disease (CAD) outcomes.

Methods

We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data containing information on CAD outcomes from medical record review. Using a published bead‐based assay method, we measured 10 types of anti–Cit‐fibrinogens. We applied a score test to determine the association between the anti–Cit‐fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti–Cit‐fibrinogens clustered into groups. Each group was then additionally tested for association with CAD. Sensitivity analyses were also performed using a published International Classification of Disease, Ninth Revision code group for ischemic heart disease (IHD) as the outcome.

Results

We studied 1,006 RA subjects (mean ± SD age 61.0 ± 13.0 years; 72.2% anti–cyclic citrullinated peptide positive). As a group, anti–Cit‐fibrinogen was associated with CAD (P = 1.1 × 10^?4). From the PCA analysis, we observed 3 main groups, of which only 1 group, containing 7 of the 10 anti–Cit‐fibrinogens, was significantly associated with CAD outcomes (P = 0.015). In the sensitivity analysis, all anti–Cit‐fibrinogens as a group remained significantly associated with IHD (P = 2.9 × 10^?4).

Conclusion

Anti–Cit‐fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies.

     

Nationwide Experience With Off‐Label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Objective

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Methods

In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti–IL‐1 treatment for at least 6 months were reviewed.

Results

In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18–68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1–48), and the mean colchicine dose was 1.7 mg/day (range 0.5–4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti–IL‐1 treatment was used because of colchicine‐resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6–98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine‐resistant FMF patients were attack free. Serum levels of C‐reactive protein, erythrocyte sedimentation rate, and 24‐hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced.

Conclusion

Anti–IL‐1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine‐resistant FMF patients.

     

Clinical and Serologic Features in Patients With Incomplete Lupus Classification Versus Systemic Lupus Erythematosus Patients and Controls

Objective

Incomplete lupus erythematosus (ILE) involves clinical and/or serologic manifestations consistent with but insufficient for systemic lupus erythematosus (SLE) classification. Because the nature of ILE is poorly understood and no treatment recommendations exist, we examined the clinical manifestations, medication history, and immunologic features in a diverse collection of ILE and SLE patients.

Methods

Medical records of subjects enrolled in the Lupus Family Registry and Repository were reviewed for medication history and American College of Rheumatology (ACR) classification criteria to identify ILE patients (3 ACR criteria; n = 440) and SLE patients (≥4 ACR criteria; n = 3,397). Participants completed the Connective Tissue Disease Screening Questionnaire. Anticardiolipin and plasma B lymphocyte stimulator (BLyS) were measured by enzyme‐linked immunosorbent assay, antinuclear antibodies (ANAs) by indirect immunofluorescence, and 13 autoantibodies by bead‐based assays.

Results

On average, ILE patients were older than SLE patients (46.2 years versus 42.0 years; P < 0.0001), and fewer ILE patients were African American (23.9% versus 32.2%; P < 0.001). ILE patients exhibited fewer autoantibody specificities than SLE patients (1.3 versus 2.6; P < 0.0001) and were less likely to have ANA titers ≥1:1,080 (10.5% versus 19.5%; P < 0.0001). BLyS levels were intermediate in ILE patients (controls < ILE; P = 0.016; ILE < SLE; P = 0.008). Pericarditis, renal, or neurologic manifestations occurred in 12.5% of ILE patients and were associated with non–European American race/ethnicity (P = 0.012). Hydroxychloroquine use increased over time, but was less frequent in ILE than SLE patients (65.2% versus 83.1%; P < 0.0001).

Conclusion

Although usually characterized by milder symptoms, ILE manifestations may require immunomodulatory treatments. Longitudinal studies are necessary to understand how ILE affects organ damage and future SLE risk, and to delineate molecular pathways unique to ILE.

     

Large‐Vessel Dilatation in Giant Cell Arteritis: A Different Subset of Disease?

Objective

To compare patients with large‐vessel giant cell arteritis (LV‐GCA) characterized by wall thickening, stenosis, and/or occlusion of subclavian arteries to those with subclavian dilatation.

Methods

For the purposes of the present retrospective study, 2 different subsets of LV‐GCA were identified and compared from an established cohort of patients with radiographic evidence of subclavian artery vasculitis secondary to GCA: LV‐GCA with wall thickening, stenosis, and/or occlusion of subclavian arteries (Group 1), and LV‐GCA with dilatation of subclavian arteries without wall thickening or stenotic changes (Group 2).

Results

The study included 109 patients in Group 1 and 11 in Group 2. Large‐vessel involvement secondary to GCA was diagnosed significantly later in patients from Group 2 compared to those from Group 1 (median 15.3 versus 0.0 months; P = 0.010). Compared to patients from Group 1, those from Group 2 were more frequently male (17% versus 45%; P = 0.027), ever smokers (42% versus 73%; P = 0.048), and more frequently had a history of coronary artery disease (11% versus 36%; P = 0.018). At LV‐GCA diagnosis, 10 of the 11 patients (91%) from Group 2 had aortic dilatation compared to 13 of 109 patients (12%) from Group 1 (P < 0.001). During the followup period, the prevalence of aortic aneurysm was significantly higher in patients from Group 2 compared with those from Group 1 (64% versus 7% at 5 years; P < 0.001).

Conclusion

Two different subsets of LV‐GCA were identified. Given the strong association between subclavian artery dilatation and aortic aneurysm, such patients should be evaluated and monitored carefully for aortic dilatation.

     

Evaluation of a Methodologic Approach to Define an Inception Cohort of Rheumatoid Arthritis Patients Using Administrative Data

Objective

Identifying incident rheumatoid arthritis (RA) is desirable in order to create inception cohorts. We evaluated an approach to identify incident RA in health plan claims data.

Methods

Both Medicare and commercial claims data were linked to Corrona, a US RA registry. We evaluated the accuracy of year of RA onset in the registry (gold standard) versus different claims algorithms, varying International Classification of Diseases, Ninth Revision codes for RA/arthritis, duration of health plan enrollment preceding diagnosis (minimum of 1 versus 2 years), and use of RA medications. Results were reported as positive predictive values (PPVs) of the claims‐based algorithm for incident RA.

Results

Depending on the algorithm tested and whether patients were enrolled in Medicare or the commercial health plan, the PPVs for incident RA ranged from 68–81%. A 2‐year clean period free of all RA‐related diagnoses and medications was somewhat more optimal although, by comparison, a 1‐year clean period yielded similar PPVs and retained approximately 90% more RA patients for analysis.

Conclusion

Claims‐based algorithms can accurately identify incident RA.

     

Relationship Between Knee Pain and Infrapatellar Fat Pad Morphology: A Within‐ and Between‐Person Analysis From the Osteoarthritis Initiative

Objective

Inflammation is known to be strongly associated with knee pain in osteoarthritis. The infrapatellar fat pad represents a potential source of proinflammatory cytokines. Yet the relationship between infrapatellar fat pad morphology and osteoarthritis symptoms is unclear.

Methods

Here we investigate quantitative imaging parameters of infrapatellar fat pad morphology between painful versus contralateral pain‐free legs of subjects with unilateral knee pain and patients with chronic knee pain versus those of matched pain‐free control subjects. A total of 46 subjects with strictly unilateral frequent knee pain and bilateral radiographic osteoarthritis (Kellgren/Lawrence grade 2/3) were drawn from the Osteoarthritis Initiative. Further, 43 subjects with chronic knee pain over 4 years and 43 matched pain‐free controls without pain over this period were studied. Infrapatellar fat pad morphology (volume, surface area, and depth) was determined by manual segmentation of sagittal magnetic resonance images.

Results

No significant differences in infrapatellar fat pad morphology were observed between painful versus painless knees of persons with strictly unilateral knee pain (mean difference ?0.7% (95% confidence interval [95% CI] ?0.6, 0.9; P = 0.64) or between chronically painful knees versus matched painless controls (?2.1% [95% CI ?2.2, 1.1]; P = 0.51).

Conclusion

Independent of the ambiguous role of the infrapatellar fat pad in knee osteoarthritis (a potential source of proinflammatory cytokines or a mechanical shock absorber), the size of the infrapatellar fat pad does not appear to be related to knee pain.

     

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty‐Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts

Objective

To assess the 5‐year progression of erosions and joint space narrowing (JSN ) and their associations with rheumatoid factor (RF ) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years.

Methods

Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS ) method in the Early Rheumatoid Arthritis Study (ERAS ), 1986–2001, and the Early Rheumatoid Arthritis Network (ERAN ), 2002–2013. Mixed‐effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN , separately. RF , along with age, sex, and baseline markers of disease activity were controlled for.

Results

A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS , ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy‐four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF ‐positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855).

Conclusion

Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease‐modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment.

     

Impact of Obesity and Adiposity on Inflammatory Markers in Patients With Rheumatoid Arthritis

Objective

The C‐reactive protein (CRP ) level and erythrocyte sedimentation rate (ESR ) are important disease activity biomarkers in rheumatoid arthritis (RA ). This study aimed to determine to what extent obesity biases these biomarkers.

Methods

Body mass index (BMI ) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross‐sectional Body Composition (BC ) cohort (n = 451), including whole‐body dual x‐ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA ) registry (n = 1,652), using multivariable models stratified by sex. For comparison, associations were evaluated in the general population using the National Health and Nutrition Examination Survey.

Results

Among women with RA and in the general population, greater BMI was associated with greater CRP levels, especially among women with severe obesity (P < 0.001 for BMI ≥35 kg/m² versus 20–25 kg/m²). This association remained after adjustment for joint counts and patient global health scores (P < 0.001 in BC and P < 0.01 in VARA ), but was attenuated after adjustment for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest. In men with RA , lower BMI was associated with higher CRP levels and ESR , contrasting with positive associations among men in the general population.

Conclusion

Obesity is associated with higher CRP levels and ESR in women with RA . This association is related to fat mass and not RA disease activity. Low BMI is associated with higher CRP levels in men with RA ; this unexpected finding remains incompletely explained but likely is not a direct effect of adiposity.

     

Does Education Level Mitigate the Effect of Poverty on Total Knee Arthroplasty Outcomes?

Objective

Total knee arthroplasty (TKA) outcomes are worse for patients from poor neighborhoods, but whether education mitigates the effect of poverty is not known. We assessed the interaction between education and poverty on 2‐year Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function.

Methods

Patient‐level variables from an institutional registry were linked to US Census Bureau data (census tract [CT] level). Statistical models including patient and CT‐level variables were constructed within multilevel frameworks. Linear mixed‐effects models with separate random intercepts for each CT were used to assess the interaction between education and poverty at the individual and community level on WOMAC scores.

Results

Of 3,970 TKA patients, 2,438 (61%) had some college or more. Having no college was associated with worse pain and function at baseline and 2 years (P = 0.0001). Living in a poor neighborhood (>20% below poverty line) was associated with worse 2‐year pain (P = 0.02) and function (P = 0.006). There was a strong interaction between individual education and community poverty with WOMAC scores at 2 years. Patients without college living in poor communities had pain scores that were ~10 points worse than those with some college (83.4% versus 75.7%; P < 0.0001); in wealthy communities, college was associated with a 1‐point difference in pain. Function was similar.

Conclusion

In poor communities, those without college attain 2‐year WOMAC scores that are 10 points worse than those with some college; education has no impact on TKA outcomes in wealthy communities. How education protects those in impoverished communities warrants further study.

     

Efficacy of a Work Disability Prevention Program for People with Rheumatic and Musculoskeletal Conditions: A Single‐Blind Parallel‐Arm Randomized Controlled Trial

Objective

Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over 2 years among people with rheumatic and musculoskeletal conditions.

Methods

Eligibility criteria for this single‐blind, parallel‐arm randomized trial included ages 21–65 years, 15 or more hours/week employment, a self‐reported doctor‐diagnosed rheumatic or musculoskeletal condition, and concern about staying employed. The intervention consisted of a 1.5‐hour meeting, an action plan, written materials on employment supports, and telephone calls at 3 weeks and 3 months. Control group participants received the written materials. The primary outcome was the Work Limitations Questionnaire (WLQ) output job demand subscale. The secondary outcome was work loss. Intent‐to‐treat analyses were performed.

Results

Between October 2011 and January 2014, 652 individuals were assessed for eligibility. A total of 287 participants were randomized: 143 intervention and 144 control participants. In total, 264 participants (92%) completed 2‐year data collection. There was no difference in the mean ± SD WLQ change scores from baseline to 2‐year followup (?8.6 ± 1.9 intervention versus ?8.3 ± 2.2 control; P = 0.93). Of the 36 participants who experienced permanent work loss at 2 years, 11 (8%) were intervention participants and 25 (18%) control participants (P = 0.03).

Conclusion

The intervention did not have an effect on work limitations but reduced work loss. The intervention can be delivered by trained rehabilitation therapists.

     

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics,Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial

Objective

To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions.

Methods

We performed a randomized controlled trial among first‐degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE‐RA) group received the web‐based PRE‐RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans‐theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk–related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post‐intervention. Subjects reported behavior change at each visit. We performed intent‐to‐treat analyses using generalized estimating equations for the binary outcome.

Results

Subjects randomized to PRE‐RA were more likely to increase ladder scores over post‐intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE‐RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age‐adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE‐RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18).

Conclusion

Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk–related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes, such as RA‐related autoantibody production or RA development.

     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Albuminuria in Rheumatoid Arthritis: Associations With Rheumatoid Arthritis Characteristics and Subclinical Atherosclerosis

Objective

Albuminuria is a marker for subclinical cardiovascular disease (CVD ) in the general population. It is uncertain whether this association is present in patients with rheumatoid arthritis (RA ), a population with increased atherosclerosis and CVD events.

Methods

Urine albumin from a spot morning collection was measured, and the urine albumin‐to‐creatinine ratio (uACR ) was calculated for RA patients and a population‐based sample of demographically matched non‐RA controls. Associations of elevated uACR (≥25 mg/gm for women and ≥17 mg/gm for men) with CVD risk factors and measures of atherosclerosis (coronary artery calcification, ultrasound‐determined maximal intima‐media thickness of the common carotid artery and internal carotid artery [ICA ], and the presence of focal plaque in the ICA ) were compared cross‐sectionally according to RA status.

Results

We compared 196 RA patients with 271 non‐RA controls. Elevated uACR was found in 18% of the RA patients compared with 17% of the controls (P = 0.89). After adjustment, RA was associated with 57% lower odds of elevated uACR (P = 0.016). Higher serum creatinine levels and hypertension were both strongly and significantly associated with elevated uACR in the control group but not in the RA group (both P for interaction < 0.05). Among RA characteristics, the adjusted prevalence of elevated uACR among those treated with tumor necrosis factor inhibitors was less than half that among those not so treated (9% versus 20%, respectively; P = 0.047).

Conclusion

There was no association in the RA group of elevated uACR with measures of atherosclerosis or with several key cardiometabolic risk factors, which suggests a lower usefulness of elevated uACR as an indicator of subclinical CVD in RA.

     

Bone Mineral Density and the Risk of Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project

Objective

To address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes.

Methods

Using data (n = 1,474) from the Johnston County Osteoarthritis Project's first (1999–2004) and second (2005–2010) followup of participants ages ≥45 years, we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual x‐ray absorptiometry, and participants were classified into sex‐specific quartiles (low, intermediate low, intermediate high, and high). Radiographic OA (ROA) was defined as development of Kellgren/Lawrence grade ≥2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

Median followup time was 6.5 years (range 4.0–10.2 years). In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR 0.52 [95% CI 0.31–0.86] and 0.56 [95% CI 0.31–0.86], respectively; P = 0.024 for trend); high BMD was not associated (HR 0.69 [95% CI 0.45–1.06]) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (HR 2.15 [95% CI 1.40–3.30] and 1.65 [95% CI 1.02–2.67], respectively; P = 0.325 for trend); similar associations were seen with knee ROA.

Conclusion

Our findings suggest that higher BMD may reduce the risk of hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA.

     

Patient Perception of Disease‐Related Symptoms and Complications in Relapsing Polychondritis

Objective

To assess patient‐reported symptoms and burden of disease in relapsing polychondritis (RP).

Methods

Patients with RP completed a disease‐specific online survey to identify symptoms attributed to illness. Patients were divided into subgroups based upon presence or absence of ear/nose, airway, or joint involvement. Pathway to diagnosis, treatment, and disease‐related complications were assessed within each subgroup.

Results

Data from 304 respondents were included in this analysis. Prior to diagnosis, most patients with RP went to the emergency room (54%), saw > 3 physicians (54%), and had symptoms for >5 years (64%). A concomitant diagnosis of fibromyalgia and absence of ear/nose or joint involvement was associated with diagnostic delay >1 year. Common diagnoses prior to RP diagnosis included asthma in patients with airway involvement (35% versus 22%; P = 0.03) and ear infection in patients with ear/nose involvement (51% versus 6%; P < 0.01). Patients with joint involvement were more likely to receive a glucocorticoid‐sparing agent (85% versus 13%; P < 0.01). Most patients reported a major complication, including disability (25%), tracheomalacia (16%), or hearing loss (34%). Patients with airway involvement reported more tracheomalacia (20% versus 4%; P < 0.01). Disability (24% versus 7%; P < 0.01) and hearing loss (39% versus 11%; P < 0.01) were prevalent in the joint involvement subgroup.

Conclusion

Patient‐reported data in RP highlight a significant burden of disease. Patterns of organ involvement may lead to diagnostic delay and influence treatment decisions, ultimately impacting the development of disease‐related complications. Timely diagnosis, standardization of treatment approaches, and prevention of disease‐related complications are major unmet needs in RP.

     

Natural History and Predictors of Progression to Sjögren's Syndrome Among Participants of the Sjögren's International Collaborative Clinical Alliance Registry

Objective

To explore changes in the phenotypic features of Sjögren's syndrome (SS), and in SS status among participants in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry over a 2–3‐year interval.

Methods

All participants in the SICCA registry who were found to have any objective measures of salivary hypofunction, dry eye, focal lymphocytic sialadenitis in minor salivary gland biopsy, or anti‐SSA/SSB antibodies were recalled over a window of 2 to 3 years after their baseline examinations to repeat all clinical examinations and specimen collections to determine whether there was any change in phenotypic features and in SS status.

Results

As of September 15, 2013, a total of 3,514 participants had enrolled in SICCA, and among 3,310 eligible, 771 presented for a followup visit. Among participants found to have SS using the 2012 American College of Rheumatology (ACR) classification criteria, 93% again met the criteria after 2 to 3 years, and this proportion was 89% when using the 2016 ACR/European League Against Rheumatism (EULAR) criteria. Among those who did not meet ACR or ACR/EULAR criteria at baseline, 9% and 8%, respectively, had progressed and met them at followup. Those with hypergammaglobulinemia and hypocomplementemia at study entry were, respectively, 4 and 6 times more likely to progress to SS by ACR criteria than those without these characteristics (95% confidence interval 1.5–10.1 and 1.8–20.4, respectively).

Conclusion

While there was stability over a 2–3‐year period of both individual phenotypic features of SS and of SS status, hypergammaglobulinemia and hypocomplementemia at study entry were predictive of progression to SS.

     

Radiographic Progression in Psoriatic Arthritis Achieving a Good Response to Treatment: Data Using Newer Composite Indices of Disease Activity

Objective

To compare radiographic outcomes according to the magnitude of the response utilizing 3 new psoriatic composite disease activity measures (the Psoriatic Arthritis Disease Activity Score [PASDAS], the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise [GRACE], and the Disease Activity in PsA [DAPSA]).

Methods

The data were taken from the GO‐REVEAL data set, a large randomized, double‐blind study that evaluated the safety and efficacy of 2 doses of the tumor necrosis factor inhibitor golimumab in subjects with active psoriatic arthritis (PsA). Response criteria at 24 weeks were applied across the whole data set, irrespective of treatment group. Radiographic scores at baseline and 24 weeks were assessed using the modified Sharp/van der Heijde method for PsA.

Results

Overall, for each measure, radiographic progression was significantly greater in subjects with a moderate or poor outcome, and absent in those with a good outcome. The proportion of subjects without radiographic progression in the good outcome group was 83% using the PASDAS (χ² = 7.9; P = 0.02), 80% using the GRACE (χ² = 5.8; P = 0.05), and 76% using the DAPSA (χ² = 3.4; P = 0.19).

Conclusion

Response criteria for disease‐specific composite measures enable separation between groups in terms of radiographic progression and may therefore be used as suitable targets for interventional studies, as well as in the clinic.

     

Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration

Objective

To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

Methods

We enrolled 135 patients followed in 3 tertiary‐care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann‐Whitney U test, Wilcoxon's signed rank test for paired samples, chi‐square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan‐Meier curves were constructed, each one at the mean of entered covariates.

Results

The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3–109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic‐onset disease compared to the rest of the JIA patients (Mantel‐Cox χ² = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel‐Cox χ² = 9.06, P < 0.002). No other clinical variable was significantly associated with a long‐lasting remission.

Conclusion

Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.