Meaningful Outcome Measures for Pediatrc Lupus Trials

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DESCRIPTION (provided by applicant): Systemic Lupus Erythematosus (SLE) is a severe autoimmune disease with rising mortality that targets primarily young women of US minorities and 20% of all patients are diagnosed during childhood (cSLE). Children with cSLE have a worse prognosis than adults. There are only 3 medications (aspirin, hydroxychloroquine, gluco-corticoids) that have ever been fully approved for adult SLE by the U.S. Food and Drug Administration, but there are none for cSLE. Lack of testing new drugs is likely one of the main reasons why the 10-year survival of SLE and cSLE patients at 85% has not improved for over a decade. Randomized clinical trials (RCTs) in SLE, but especially cSLE, are hindered by the lack of standardized high-quality surrogate markers to verify the effects of new drugs within the short time frames considered in RCTs. The central hypothesis of this application is that modified RCT outcomes parameters (surrogate markers) of adult SLE can be used to assess treatment responses of children with cSLE. We propose to enroll 100 children with cSLE from 5 pediatric rheumatology centers organized in Childhood Arthritis & Rheumatology Research Alliance. Subjects will be assessed every 3 months (follow-up: 1.5 yrs). Previously developed RCT software will be used for web-based data entry and study management. To test the central hypothesis of the application the following 3 specific aims are pursued: 1: To assess the proposed American College of Rheumatology Ad-hoc Committee criteria for minimal important differences in disease activity of adults with SLE for their validity when used in cSLE. 2: To prospectively validate the preliminary definitions of improvement for cSLE that have been proposed by the Pediatric Rheumatology International Trial Organization (PRINTO) and the Prediatric Rheuamtology Collaborative Study Group (PRCSG). 3: To newly develop preliminary criteria of disease flare in cSLE based on the set of cSLE core response variables that have been previously developed by PRINTO/PRCSG. Our expectations are that this study will provide validated surrogate markers of changes in global diseases to be used as primary response parameters of future cSLE RCTs. We will identify within a short period of time urgently required RCT outcome parameters to directly measure the effects of cSLE treatments. Validated surrogate markers will simplify the measurement of drug effects and provide standards to uniformly judge the effects of study medications on the course of cSLE. Specifically, we test whether these parameters can be used for adults and children with SLE, possibly being able to confirm that both groups can be studied in future, drug trials concurrenlty based on the validity of similar response parameters. This would facilitate SLE RCTs in general and further promote cSLE research in particular.