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1.  Disease Activity and Fatigue in Juvenile Idiopathic Arthritis 
Arthritis care & research  2013;65(3):391-397.
Objective
To examine the association between parent/proxy- and child-reported fatigue and disease activity in children with polyarticular, extended oligoarticular, and persistent oligoarticular juvenile idiopathic arthritis (JIA).
Methods
We enrolled a cross-sectional cohort of 309 children recruited from the Seattle Children’s Hospital rheumatology clinic from 2009–2011. Parents and children completed the PedsQL Multidimensional Fatigue Scales. The parent/proxy, child, and/or physician provided additional disease activity data at each clinic visit, including active joint count, pain, and the Childhood Health Assessment Questionnaire (C-HAQ). Disease activity was dichotomized as active or inactive using the American College of Rheumatology provisional criteria for clinically inactive disease. The Juvenile Arthritis Disease Activity Score (JADAS) was also calculated. Linear regression was used to examine the associations between fatigue and disease activity.
Results
Associations among fatigue, clinically inactive disease, and the JADAS were not statistically significant after controlling for pain. In the multivariable models of fatigue, the C-HAQ and parent/child-reported disease activity were significantly associated with fatigue; however, only the C-HAQ remained significantly associated after adjustment for pain. The C-HAQ and parent/child-reported disease activity explained 17% and 30% of the variance in fatigue for the parent/proxy- and child-reported multivariable models, respectively.
Conclusion
In this cohort, functional ability, as measured by the C-HAQ, was significantly associated with fatigue. Child-and parent/proxy-reported pain were important confounders of the relationship between fatigue and disease activity. Routinely incorporating pain and fatigue into interventional and observational trials of JIA will enable better delineation of the relationships between these variables.
doi:10.1002/acr.21801
PMCID: PMC4117647  PMID: 22807336
2.  Disease Modifying Anti-Rheumatic Drug Use in the Treatment of Juvenile Idiopathic Arthritis: A Cross-Sectional Analysis of the CARRA Registry 
The Journal of rheumatology  2012;39(9):1867-1874.
Objective
To characterize disease modifying anti-rheumatic drug (DMARD) use for children with juvenile idiopathic arthritis (JIA) in the United States and determine patient factors associated with medication use.
Methods
We analyzed cross-sectional baseline enrollment data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from May 2010 through May 2011 for children with JIA. Current and prior medication use was included. We used parsimonious backward stepwise logistic regression models to calculate odds ratios (OR) to estimate associations between clinical patient factors and medication use.
Results
We identified 2,748 children with JIA with a median disease duration of 3.9 years from 51 U.S. clinical sites. Overall, 2,023 (74%) had ever received a non-biologic DMARD and 1,246 (45%) had ever received a biologic DMARD. Among children without systemic arthritis, methotrexate use was most strongly associated with uveitis (OR 5.2; 95% confidence interval [3.6–7.6]), cyclic citrullinated peptide antibodies (4.5 [1.7–12]), and extended oligoarthritis (4.1 [2.5–6.6]). Among children without systemic arthritis, biologic DMARD use was most strongly associated with rheumatoid factor positive (RF+) polyarthritis (4.3 [2.9–6.6]), psoriatic arthritis (3.0 [2.0–4.4]), and uveitis (2.8 [2.1–3.7]). Among children with systemic arthritis, 160 (65%) ever received a biologic DMARD; TNF inhibitor use was associated with polyarthritis (2.5 [3.8–16]) while IL-1 inhibitor use was not.
Conclusions
Approximately three-quarters of all children with JIA in the CARRA Registry received non-biologic DMARDs. Nearly one-half received biologic DMARDs, and their use was strongly associated with rheumatoid factor positive polyarthritis, psoriatic arthritis, uveitis, and systemic arthritis.
doi:10.3899/jrheum.120110
PMCID: PMC3763075  PMID: 22859354
3.  Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis 
Arthritis and Rheumatism  2011;64(6):2012-2021.
OBJECTIVES
To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months.
METHODS
Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months.
RESULTS
By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events.
CONCLUSIONS
Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment.
doi:10.1002/art.34343
PMCID: PMC3319524  PMID: 22183975
Juvenile idiopathic arthritis; early aggressive therapy; clinical inactive disease; randomized controlled trial
4.  Management of temporomandibular joint arthritis in adult rheumatology practices: a survey of adult rheumatologists 
Background
The temporomandibular (TMJ) is frequently involved in juvenile idiopathic arthritis (JIA), however little is known about management of this joint once a patient transitions from pediatric to adult care and about how rheumatologists approach TMJ involvement in rheumatoid arthritis (RA). The objective of this project was to describe adult rheumatologists’ approaches to the diagnosis and treatment of TMJ arthritis in adults with JIA or RA.
Findings
One hundred and eighteen rheumatologists responded to an online survey of adult rheumatologists in the United States and Canada. Respondents estimated that 1-25% of their patients with RA or JIA had TMJ arthritis. Respondents reported lower rates of MRI use (19%) and higher rates of use of splinting/functional devices (50%) than anticipated. Approximately 80% of respondents reported that their practice had a standardized approach to the evaluation of patients with TMJ arthritis. The most commonly used medical therapies were non-steroid anti-inflammatory drugs, anti-tumor necrosis factor alpha medications, and methotrexate.
Conclusions
Despite the majority of respondents stating that their practices had a standardized approach to the diagnosis and treatment of TMJ disease, there nevertheless appeared to be a range of practices reported. Standardizing the evaluation and treatment of TMJ arthritis across practices may benefit both adult and pediatric patients.
doi:10.1186/1546-0096-10-26
PMCID: PMC3511809  PMID: 22906004
Temporomandibular joint arthritis; Juvenile idiopathic arthritis; Rheumatoid arthritis
8.  Sleep Disturbances and Neurobehavioral Functioning in Children with and without Juvenile Idiopathic Arthritis 
Arthritis care & research  2011;63(7):1006-1012.
Objective
To compare sleep disturbances and neurobehavioral function in children with juvenile idiopathic arthritis (JIA) to age-sex matched control children.
Methods
Parents of and children (N = 116) 6–11 years of age with (n = 70) and without (n = 46) JIA participated. Parents completed questionnaires on sleep habits, sleep behavior and school competence of their children; children completed computerized neurobehavioral performance tests.
Results
Compared to control children, children with JIA had a statistically significant (p < .001) greater mean overall sleep disturbance score and higher scores on 6 of 8 subscales (all p < .03) on the children’s sleep habits questionnaire (CSHQ). There were no group differences on neurobehavioral performance test scores. However, children, regardless of group, with an overall CSHQ score above an established cut off for clinically significant sleep disturbances had slower mean simple reaction time (t = −2.2, p<.03) and mean 5-choice reaction time (t = −2.3, p<.02) compared to those below the cutoff score. The CHSQ overall sleep disturbance score predicted reaction time (p <0.009), after controlling for age, IQ, medication, and group.
Conclusion
Children with JIA have more parent reported sleep disturbances, but performed as well as control children on a series of standardized computer tests of neurobehavioral performance. Children with more disturbed sleep had slower reaction times.
doi:10.1002/acr.20469
PMCID: PMC3128173  PMID: 21452251
9.  The 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis 
Arthritis and rheumatism  2010;62(9):2582-2591.
Objective
The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set.
Methods
Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of “developing RA,” complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis.
Results
The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach.
Conclusion
The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.
doi:10.1002/art.27580
PMCID: PMC3077961  PMID: 20872596
10.  Anti-Citrullinated Peptide Antibody (ACPA) Assays and their Role in the Diagnosis of Rheumatoid Arthritis 
Arthritis and rheumatism  2009;61(11):1472-1483.
Increasingly, assays for the detection of anti-citrullinated peptide antibodies (ACPA) are used in RA diagnosis. This review summarizes the biologic basis and development of ACPA assays, available ACPA assays and their performance characteristics, and diagnostic properties of ACPA alone and compared to rheumatoid factor (RF) in early RA. We also review correlations, precision, costs and cost-effectiveness, availability, stability and reproducibility of the available assays. Taken together, data indicate that ACPA has a higher specificity than RF for early RA, good predictive validity, high sensitivity, apparent cost-effectiveness and good stability and reproducibility. Given its superior performance characteristics and increasing availability, ACPA is emerging as the most useful single assay for the diagnosis of RA.
doi:10.1002/art.24827
PMCID: PMC2859449  PMID: 19877103
anti-citrullinated peptide antibody; rheumatoid factor; anti-CCP; ACPA; RF; diagnosis; rheumatoid arthritis; early arthritis
11.  The temporomandibular joint in juvenile idiopathic arthritis: frequently used and frequently arthritic 
Recent recognition of the markedly high prevalence of temporomandibular joint (TMJ) arthritis in children with juvenile idiopathic arthritis (JIA) coupled with the significant morbidity associated with TMJ damage has prompted increased interest in both the clinical and pathological aspects of TMJ arthritis. This review focuses on the prevalence of TMJ arthritis in JIA, the imaging modalities used to detect TMJ arthritis, and the treatment of TMJ arthritis in children with JIA.
doi:10.1186/1546-0096-7-11
PMCID: PMC2694194  PMID: 19480670

Results 1-11 (11)