Natasha M. Ruth

Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus

To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).

Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis

To assess the efficacy and safety of rilonacept, an interleukin‐1 inhibitor, in a randomized, double‐blind, placebo‐controlled trial.

Algorithm development for corticosteroid management in systemic juvenile idiopathic arthritis trial using consensus methodology

BackgroundThe management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT).MethodsThe 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process. The panel used a modified Delphi Method consisting of an on-line questionnaire, followed by a one day face-to-face consensus conference. Consensus was defined as ≥ 75% agreement. For items deemed essential but when consensus on critical values was not achieved, simple majority vote drove the final decision.ResultsThe panel identified criteria for initiating or increasing corticosteroids. These included the presence or development of anemia, myocarditis, pericarditis, pleuritis, peritonitis, and either complete or incomplete macrophage activation syndrome (MAS). The panel also identified criteria for tapering corticosteroids which included absence of fever for ≥ 3 days in the previous week, absence of poor physical functioning, and seven laboratory criteria. A tapering schedule was also defined.ConclusionThe expert panel established consensus regarding corticosteroid management and an algorithm for steroid dosing that was well accepted and used by RAPPORT investigators. Developed specifically for the RAPPORT trial, further study of the algorithm is needed before recommendation for more general clinical use.

Juvenile idiopathic arthritis: management and therapeutic options

The goals of treatment for juvenile idiopathic arthritis (JIA) include: suppression of inflammation, achievement of remission, relief of pain, maintenance of function and doing so with minimal toxicity. Important discoveries over the past 10–15 years have led to more targeted treatments for children with JIA. The International League of Associations for Rheumatology (ILAR) classification system for childhood arthritides, better assessment tools for clinical response, improved definitions of remission, new imaging techniques and evidence in gene expression profiling have all contributed to the development of more targeted treatments. Nonsteroidal anti-inflammatory agents still have a role in mild disease and intra-articular steroid injections continue to be used most commonly in patients with oligoarticular JIA. Disease-modifying agents such as methotrexate have demonstrated efficacy and safety; however, in many patients, the disease remains active despite this treatment. These children now receive more targeted treatment including the tumor necrosis factor alpha (TNFα) inhibitors, interleukin-1 blockade, interleukin-6 blockade, selective costimulation modulators and selective B-cell blockade. The biologic targeted therapies have changed the strategy in which we treat our children with JIA; however, there remains much to be learned about the long-term effects and safety of these medicines.

The RAndomized Placebo Phase Study Of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

To assess the efficacy and safety of rilonacept, an interleukin‐1 inhibitor, in a randomized, double‐blind, placebo‐controlled trial.

Cognitive Performance Scores for the Pediatric Automated Neuropsychological Assessment Metrics in Childhood-Onset Systemic Lupus Erythematosus.

To develop and initially validate a global cognitive performance score (CPS) for the Pediatric Automated Neuropsychological Assessment Metrics (PedANAM) to serve as a screening tool of cognition in childhood lupus.

Pediatric clinical research.

Purpose of reviewThis review will focus on childhood-onset systemic lupus erythematosus, juvenile idiopathic arthritis, and juvenile dermatomyositis, with special interest on strategies to improve the health-related quality of life in these conditions. Recent findingsThe contribution of plasma insulin levels, lipoproteins, markers of oxidized state (including nitric oxide metabolites, isoprostanes) and autoantibodies to oxidized low-density lipoprotein to risk for atherosclerosis has been studied in childhood-onset systemic lupus erythematosus. Elevated serum levels of myeloid-related protein-8 (also called S100A8) and myeloid-related protein-14 (S100A9) in children with juvenile idiopathic arthritis can indicate clinically occult disease activity. Serum levels of S100A12 correlate with disease activity in juvenile idiopathic arthritis. Magnetic resonance imaging T2 relaxation times in weight-bearing cartilage in patients with juvenile idiopathic arthritis may help with early detection of cartilage changes. Quantitative computed tomography commonly shows decreased muscle mass and abnormal bone geometry in juvenile idiopathic arthritis patients. In patients with juvenile idiopathic arthritis who do not respond to oral methotrexate, subcutaneous methotrexate dosing was frequently successful. Duration of inactive disease while a patient is receiving methotrexate does not decrease the frequency of flaring of disease once methotrexate is discontinued. Residual synovial inflammation seems to be a stronger influence on the rate of relapse. In juvenile dermatomyositis, the quantitative magnetic resonance imaging T2 relaxation time and overexpression of Class I major histocompatibility complex in early juvenile dermatomyositis are reported. Intravenous cyclophosphamide in refractory juvenile dermatomyositis and tacrolimus ointment for the dermatologic manifestations of juvenile dermatomyositis seem promising. SummaryProgress has been made in the diagnosis and treatment of childhood-onset systemic lupus erythematosus, juvenile idiopathic arthritis, and juvenile dermatomyositis.

Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest pediatric nephrology consortium and the childhood arthritis and rheumatology research alliance

BackgroundThere is no clear consensus regarding optimal indications or timing of initial or repeat kidney biopsy in the management of pediatric systemic lupus erythematosus (pSLE).MethodsA web-based survey was designed to assess current practice patterns among pediatric nephrologists and pediatric rheumatologists and distributed to members of Midwest Pediatric Nephrology Consortium (MWPNC) and Childhood Arthritis and Rheumatology Research Alliance (CARRA).ResultsRespondents included 111 rheumatologists and 71 nephrologists from 65 and 34 centers, respectively. Numbers of years in sub-specialty practice were comparable. Rheumatologists and nephrologists frequently collaborate in the care of children with lupus nephritis (LN). More than 90 % of respondents refer patients to each either other after diagnosing LN. Over 60 % describe shared decision making regarding when to perform kidney biopsy and how to interpret biopsy findings. Many pediatric nephrologists consider biopsy to be of higher risk for complication in pSLE and alter their standard pre-or post-biopsy management.ConclusionsIt is uncommon for pediatric nephrologists to manage LN without input from pediatric rheumatologists and vice versa. Consensus exists between specialties in general, and practice differences that exist occur between individual physicians rather than between specialties. A systematic approach to biopsy may result in improved health related outcomes in pSLE.

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 <

Advances in the care of children with lupus nephritis.

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.