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Background: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs)., Methods: Children aged ≥2 to <18 years with rheumatoid-factor-positive or -negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database., Results: A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use., Conclusions: The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive., Trial Registration: ClinicalTrials.gov identifier NCT00688545.

Objective: There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (JIA) among pediatric rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available will result in better health outcomes for polyarticular JIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for use in clinical practice to facilitate such studies., Methods: A case-based survey was administered to CARRA members to identify the common treatment approaches for new-onset polyarticular JIA. Two face-to-face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, end points, and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans, and developed medication dosing and monitoring recommendations., Results: The initial case-based survey identified significant variability among treatment approaches for new-onset polyarticular JIA. We developed 3 CTPs based on treatment strategies for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a step-up plan (nonbiologic disease-modifying antirheumatic drug [DMARD] followed by a biologic DMARD), an early combination plan (nonbiologic and biologic DMARD combined within a month of treatment initiation), and a biologic only plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face-to-face meeting., Conclusion: Three standardized CTPs were developed for new-onset polyarticular JIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of polyarticular JIA., (Copyright © 2014 by the American College of Rheumatology.)

Objectives: This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE)., Methods: The SRI considers changes in the SELENA-SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA-SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined., Results: The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change., Conclusions: The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.

Objective: To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA)., Methods: In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D-dimer and myeloid-related proteins [MRPs]) were also evaluated., Results: Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment-related adverse events were observed., Conclusion: Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated., (Copyright © 2013 by the American College of Rheumatology.)

Urban populations present particular challenges for medical providers. Patients are extremely diverse, with varied socioeconomic, cultural, and ethnic backgrounds. Physicians caring for children with juvenile idiopathic arthritis must be prepared to interact effectively with many types of families who bring with them varied experiences and expectations. Pediatric rheumatologists should be familiar with patient characteristics that can influence disease outcomes. Access to care is affected by place of residence, referral delays, parental education, and the child’s insurance status. Patients of different ethnic backgrounds vary in their trust of physicians and health systems. Understanding of risk in medical decision making is influenced by ethnicity as well. Adherence also varies by ethnic group, with African American patients reporting lower adherence than Caucasian patients. Issues of doctor– patient communication and use of complementary and alternative medicine are also affected by cultural factors. Especially for physicians working in a large metropolitan area, an understanding of societal factors influencing patient behavior is essential to provide optimal care for children with juvenile idiopathic arthritis.

We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythematosus (pSLE), healthy children (n = 50), and children with juvenile idiopathic arthritis (JIA) (n = 30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p < 0.03), and unrelated to subjects' age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean +/- standard error (SE) increase of UNGAL (in ng/ml) of 11.5 +/- 6.4 or 36.6 +/- 12.1 (p < 0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with worsening disease but to a much lesser degree than UNGAL [global disease activity (mean +/- SE): 7.3 +/- 6.2 or 21%; renal disease activity: 20.2 +/- 6.0 or 51%; both p = not significant]. In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE.

Systemic lupus erythematosus (SLE) in children is a chronic multi-system disease with wide ranging effects on their quality of life (QOL). While SLE's impact on different arenas of life and well-being has been extensively examined in the adult population, its effect on children has not received adequate attention. This paper briefly discusses the multidimensional aspect of QOL, the biopsychosocial implications of SLE, factors complicating QOL measurement in the affected population, and the different generic and disease-specific scales used for measuring QOL and related constructs, and it also highlights the need for SLE-specific pediatric QOL instruments.