Joyce Hsu

Extension study of participants from the trial of early aggressive therapy in juvenile idiopathic arthritis

Objective. To follow children with juvenile idiopathic arthritis (JIA) who had completed at least 6 months of the TRial of Early Aggressive Therapy (TREAT) clinical study for an additional 2 years, describing safety of early aggressive treatment, disease activity, function, and duration of clinical inactive disease (CID) during followup. Methods. Children were treated as per provider’s discretion. Physician, patient/parent, and laboratory measures of disease status as well as safety information were collected at clinic visits every 3 months for up to 2 years. Results. Forty-eight children were followed for a mean of 28 months (range 12–42) beyond the end of the TREAT study. Half of patients were in CID for > 50% of their followup time. Overall, 88% of patients achieved CID at > 1 study visit and 54% achieved clinical remission while taking medication. Six patients were in CID for the duration of the study, and, of those, 2 achieved a full year of clinical remission while not taking medication. Active disease was mild: mean physician’s global assessment 2.4, active joint count 3.5, parent global evaluation 2.4, Childhood Health Assessment Questionnaire 0.32, erythrocyte sedimentation rate 19 mm/h, and morning stiffness 23 min. There were no serious adverse events or adverse events reported at grade 3 or higher of Common Terminology Criteria for Adverse Events. Conclusion. Early aggressive therapy in this cohort of patients with polyarticular JIA who had high initial disease activity was associated with prolonged periods of CID in the majority of patients during followup. Those not in CID had low levels of disease activity.

European ancestry decreases the risk of early onset, severe lupus nephritis in a single center, multiethnic pediatric lupus inception cohort

Purpose: To determine whether pediatric SLE patients without European ancestry are at higher risk for development of severe lupus nephritis (ISN/RPS class III, IV or V). Methods: Ninety-eight of 101 patients with pediatric SLE (age <18 years at diagnosis) were enrolled. Race/ethnicity of four grandparents, socioeconomic status (SES) and language proficiency were collected. The primary outcome was time to development of severe lupus nephritis. Results: Based on patient report of four grandparent ancestry, 29% had at least one grandparent of European ancestry (14% had all four grandparents of European ancestry). Patients without European ancestry were 46% Hispanic, 47% Asian, and 3% African American. In the entire 98 patient cohort, 12% had ≥3 different ancestries. Patients without European ancestry had significantly lower SES levels and English proficiency. There was no significant difference between patients with or without European ancestry in duration of SLE, age of onset, and lag time between symptoms and diagnosis. Patients with at least one grandparent of European ancestry had a decreased risk of developing severe lupus nephritis, which remained significant after controlling for age, gender, SES and English proficiency (hazard ratio 0.4, 95% confidence interval 0.2–0.9). Conclusion: This study demonstrates that presence of at least one grandparent of European ancestry decreases the risk of severe lupus nephritis, a finding that is not explained by measurable socioeconomic differences and language barriers.

The Juvenile Psoriatic Arthritis Cohort in the CARRA Registry: Clinical Characteristics, Classification, and Outcomes

Objective. Children with clinically diagnosed juvenile psoriatic arthritis (JPsA) who were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry (CARRA-JPsA) were classified according to pediatric International League of Associations for Rheumatology (ILAR) and adult criteria [Classification criteria for Psoriatic Arthritis (CASPAR)]. Data on demographic and clinical features at baseline and 1-year followup were analyzed and compared. Methods. Cross-sectional analysis was performed of CARRA-JPsA patients enrolled between May 2010 and December 2013 and stratified according to age at disease onset (≤ or > 4 yrs). Features of patients fulfilling ILAR and CASPAR criteria were compared at baseline and followup using chi square, Fisher’s exact, Mann-Whitney-McNemar, Wilcoxon signed rank, and t tests, as appropriate. Results. Among 361 children enrolled as CARRA-JPsA, 72.02% had symptom onset at > 4 years of age, with a male predominance and high prevalence of enthesitis. At followup, statistically significant improvements were reported in arthritis, dactylitis, enthesitis, psoriasis, sacroiliitis, and nail pitting, but not in health questionnaire (HQ) scores. Of the patients, 80.5% fulfilled ILAR criteria for JPsA. Fifty-two patients, whose disease fulfilled CASPAR criteria but had not been included in the JPsA cohort, manifested more enthesitis, sacroiliitis, inflammatory bowel disease and uveitis and less psoriasis. Conclusion. The data support division of patients with JPsA into 2 clinical subgroups, according to age at disease onset. Improvement in objective findings did not correlate with changes in HQ scores. Pediatric rheumatologists currently do not diagnose JPsA in all children whose disease manifestations meet CASPAR criteria. Unification of adult and pediatric PsA classification criteria warrants consideration.

Race, Income, and Disease Outcomes in Juvenile Dermatomyositis

Objective To determine the relationships among race, income, and disease outcomes in children with juvenile dermatomyositis (JDM). Study design Data from 438 subjects with JDM enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry were analyzed. Demographic data included age, sex, race, annual family income, and insurance status. Clinical outcomes included muscle strength, presence of rash, calcinosis, weakness, physical function, and quality of life measures. Disease outcomes were compared based on race and income. Results Minority subjects were significantly more likely to have low annual family income and significantly worse scores on measures of physical function, disease activity, and quality of life measures. Subjects with lower annual family income had worse scores on measures of physical function, disease activity, and quality of life scores, as well as weakness. Black subjects were more likely to have calcinosis. Despite these differences in outcome measures, there were no significant differences among the racial groups in time to diagnosis or duration of disease. Using calcinosis as a marker of disease morbidity, black race, annual family income <

Novel Method to Collect Medication Adverse Events in Juvenile Arthritis: Results From the Childhood Arthritis and Rheumatology Research Alliance Enhanced Drug Safety Surveillance Project

50 000 per year, negative antinuclear antibody, and delay in diagnosis >12 months were associated with calcinosis. Conclusion Minority race and lower family income are associated with worse morbidity and outcomes in subjects with JDM. Calcinosis was more common in black subjects. Further studies are needed to examine these associations in more detail, to support efforts to address health disparities in subjects with JDM and improve disease outcomes.

Adiposity in Juvenile Psoriatic Arthritis

Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product‐based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4‐year (2008–2012) EDSSP.

LL-03 Patient-reported outcomes among pediatric lupus nephritis patients treated with CARRA lupus nephritis consensus treatment plans

Objective. Adult patients with psoriatic arthritis are at increased risk for obesity and metabolic syndrome, but data regarding adiposity in children with juvenile psoriatic arthritis (JPsA) are limited. Our study assessed adiposity in children with JPsA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Methods. Patients with JPsA in the CARRA registry were divided into nonoverweight and overweight groups using recommendations from the US Centers for Disease Control, and differences in demographic and clinical characteristics between groups at baseline and after 1-year followup were assessed using chi-square test, Fisher’s exact test, T test, or Mann-Whitney U test, as appropriate. The prevalence of overweight status in the JPsA registry patients was compared to rheumatoid factor–positive and −negative polyarticular juvenile idiopathic arthritis (RF+polyJIA; RF−polyJIA) registry cohorts and the US pediatric population, using a chi-square goodness-of-fit test. Results. Overweight children represented 36.3% of this JPsA cohort (n = 320). Compared to nonoverweight children, they were significantly older at symptom onset and rheumatologist’s first assessment, and scored significantly worse on patient/physician outcome measures. At 1-year followup, changes in body mass index were not associated with changes in clinical features or outcome measures. The prevalence of overweight and obesity in patients with JPsA was significantly higher than in RF+polyJIA patients, RF−polyJIA patients, and the US pediatric population. Conclusion. In this registry, almost 1 in 5 patients with JPsA were obese and more than one-third were overweight. This is significantly more than expected compared to the US pediatric population, and appropriate longterm followup of this JPsA subgroup is warranted.

CE-31 A pilot study of consensus treatment plans for induction therapy in childhood proliferative lupus nephritis

Background The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTP) for childhood proliferative lupus nephritis (LN) induction therapy to reduce treatment variability and support comparative effectiveness research comparing efficacy and tolerability of Mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IV CYC). The CTPs specify two immunosuppression regimens (IV CYC, oral MMF) and three corticosteroid regimens (primarily oral, primarily IV, and mixed oral/IV). In addition to provider-reported outcomes, we assessed patient-reported outcomes in a pilot observational study. Methods We enrolled 41 subjects with childhood SLE from 10 CARRA sites. Subjects had new-onset biopsy proven proliferative LN and were starting MMF or IV CYC. We collected baseline demographics, disease-related features and patient-reported outcomes, including functional disability (Childhood Health Assessment Questionnaire (CHAQ), range 0–3), Health-related quality of life (HRQOL) (Child Health Questionnaire (CHQ), excellent, very good, good, poor, very poor), well-being (CHQ, range 0–10), and pain (CHAQ, 0–10). With the exception of pain, parents reported outcomes for subjects<10 years of age. We report baseline and 12 month follow-up results. Results The majority of participants were female (83%), mean age was 14 years (SD 2.6). At baseline, SLEDAI ranged from 2–34 (median 13, IQR 10–21) and glomerular filtration rate ranged from 41–151 ml/min/1.73 m2 (median 94, IQR 70–107). Baseline functional ability (CHAQ) ranged from 0–1.75 (n=38) and was abnormal (CHAQ >0) in 55.3% of subjects. By 12 months, there was improvement with 14.8% reporting abnormal functional ability. HRQOL at baseline ranged from excellent to poor (13% excellent, 37% very good, 45% good, 5% poor, n=38) and was improved at 12 months (32% excellent, 48% very good, 16%, good, 4% poor, n=25, see figure 1). Baseline median parent-reported overall wellbeing was 3.0 (IQR 2–5), with 21% reporting doing ‘very well’ (score=0). At 12 months, overall wellbeing had improved (median 0.5, IQR 0–3) with 50% reporting doing ‘very well’. Baseline patient-reported pain ranged from 0 (no pain) to 10 (very severe pain) (median 1, IQR 0–5, n=39). Pain was improved at 12 months (range 0–7, median 0, IQR 0–3, n=27).Abstract LL-03 Figure 1 HRQOL over 12 months of follow-up Conclusions Although diagnosed with a severe medical condition and experiencing functional disability, most children reported good to excellent QOL and only minimal pain. After 12 months, the proportion of patients reporting excellent QOL increased, however reduced QOL persisted for many. Further study is needed to elucidate the factors impacting overall QOL in children with SLE, and association with different treatment strategies. Acknowledgements We would like to acknowledge the CARRA Registry Investigators, Dr. Marilyn Punaro for her leadership in the CARRA lupus nephritis CTP development process and Thomas Phillips for his data management assistance. This study was supported by funding from the Arthritis Foundation, Lupus Foundation of America, CARRA and NIAMS.

Novel Method to Collect Medication Adverse Events in Juvenile Arthritis: Results From the Childhood Arthritis and Rheumatology Research Alliance Enhanced Drug Safety Surveillance Project: Enhanced Drug Safety Surveillance Project

Background Childhood-onset systemic lupus erythematous (cSLE) patients are at higher risk for renal disease than those with adult-onset disease. Mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IV CTX), commonly used for induction therapy of proliferative lupus nephritis (LN), are considered equally efficacious in adults. Comparative data in the paediatric population are lacking. To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published a consensus treatment plan (CTP) for induction therapy in childhood proliferative LN. The CTP recommended treatment with MMF or IV CTX and one of three steroid regimens: primarily oral, primarily IV, or mixed oral/IV. We report physician decision-making and 6-month response rates in a multi-centre pilot feasibility study. Materials and methods This observational study enrolled 41 cSLE patients from 10 CARRA sites. Subjects had new-onset biopsy proven class III or IV proliferative LN and were starting MMF or IV CTX. Complete renal response (CRR), defined as normal renal function, inactive urine sediment, and spot urine protein/creatinine ratio of <0.2, was measured at 6 months. Subjects were followed for up to 24 months. Baseline demographics, disease-related features, physician decision-making and achievement of CRR were compared according to induction treatment group and among steroid regimens. Results The majority of participants were female (83%) with a mean age of 14 years. There were no significant differences in demographics between MMF or IV CTX groups or among steroid regimens. Those with class IV nephritis (35.3% vs 73%, p = 0.015) and hematuria (36% vs 74% p < 0.001) were more likely to be treated with IV CTX. Physicians more often reported compliance concerns as a reason for selecting treatment for the CTX group compared to MMF (22% vs 0%, p = 0.04). Overall, physicians reported “this is what I or my group always does” as the most common reason for choice of induction agent and steroid regimen. Induction agent use did not differ significantly according to study site. Steroid regimen differed significantly by study site and induction agent. CRR at 6 months was achieved for 56% with MMF and 64% with IV CTX (p = 0.6); the study was not powered to evaluate treatment efficacy. Conclusions Class IV nephritis, hematuria and patient adherence influenced selection of induction agent. Steroid regimens differed by study site and induction regimen. To evaluate comparative effectiveness, future larger studies will be needed. Acknowledgements CARRA Registry, Lupus Foundation of America, Arthritis Foundation, Duke Clinical Research Institute. NIH T32GM00756.

Novel method to collect medication adverse events in juvenile arthritis

Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product‐based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4‐year (2008–2012) EDSSP.