Efficacy Measures for Pediatric Lupus Studies

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'ROJECT SUMMARY: Childhood-onset Systemic Lupus Erythematosus (cSLE) is a severe autoimmune disease and better medications are urgently needed to decrease its mortality. There is a fundamental gap in he knowledge of how to comprehensively measure whether clinically relevant changes in cSLE have occurred. This makes the testing of new drugs very difficult. The long-term goal of our research is to improve he prognosis of cSLE through the development and dissemination of outcome measures that will facilitate biomarker discovery, promote translational research, and the conduct of clinical trials to test the efficacy of new cSLE drugs. The objectives of this application are to prospectively validate criteria of disease flare and o develop criteria of disease remission, while establishing a common electronic data management frame- work for future cSLE studies. The central hypothesis to be tested is that the cSLE core set variables (disease activity, MD rating of disease activity, patient rating of well-being, physical function, proteinuria, damage, growth & development) are best suited to define disease flares in cSLE and that the same cSLE core set variables can be used to develop remission criteria. We propose to test the central hypothesis and achieve he study objectives by pursuing the following specific aims: 1) To develop and prospectively validate criteria of disease flare by a combination of consensus formation methodology and statistical approaches as is recommended by the American College of Rheumatology Committee on Quality Measures 2) To establish a "hildhood Arthritis Rheumatology Research Alliance (CARRA) Pediatric Lupus Registry with the goal of develop preliminary criteria of disease remission in cSLE. The approach to achieving these aims is to use data from well-defined established cohorts and newly collected information of 100 patients with extreme cSLE phenotypes to obtain real-patient information on the occurrence of flares, remission and the related changes in the cSLE core variables (>750 patient-years of follow-up; n>400). In close collaborations with Drofessional societies and by using consensus methodology (Delphi, nominal group technique), data mining techniques, and other statistical approaches quantitatively validated criteria of flare and preliminary criteria of disease remission will be developed. Our web-based data management systems will be improved for this study. Supported by NIH-funded Centers of Excellence and the CCHMC Rheumatology Clinical Trial Unit, the expected results of this application are flare criteria that can readily be used as efficacy measures of clinical trials in cSLE and preliminary criteria of remission for cSLE. The collected data will serve as the foundation for a CARRA Pediatric Lupus Registry, and a versatile web-based Lupus Study Management System will be developed and made available to the pediatric rheumatology community. This is of major significance because quantitatively validated flare criteria will facilitate clinical trials of disease modifying drugs, while remission criteria are critical to test the most potent new medications that are currently being developed. Web-based study management is cost & time saving and promotes future collaborative research. RELEVANCE TO PUBLIC HEALTH: As is suggested by the recently published NIAMS Long-Term Research Plan and by leveraging the expertise of NIH-funded Centers of Excellence, the proposed research will enhance the "tool box" of biomedical & clinical investigators and serve as a venue to improve the quality of life and prognosis of children with cSLE through the development of better drugs.