Systemic lupus erythematosus (SLE) is a disease that causes major organ damage and shortens lifespan. Early diagnosis and treatment are essential to improving outcomes for SLE patients. However, tools for the reliable identification of SLE in early stages and evidenced based approaches to early treatment are not available. We propose that individuals who are at high risk of SLE can be identified in early or preclinical stages with sufficient reliability to serve as a target population for initiating treatment with a safe therapythat has potential to delay or abort full expression of disease. This population has some elements of lupus but does not fully satisfy classification criteria, and may be referred to as incomplete lupu erythematosus (ILE). The present proposal requests support for the planning phase of a multicenter, placebo controlled trial of hydroxychloroquine in ILE patients to determine whether this intervention can ameliorate, delay or prevent progression to SLE. The planned trial will be carried out with intensive sampling for potential biomarkers to elucidate underlying disease and drug mechanisms. During the planning phase, the four cooperating sites will finalize a protocol, prepare all needed study documents and manuals, secure a source for the medication and placebo and obtain regulatory approvals. In addition, mock recruitment scenarios will be carried out to confirm that enrollment is feasible. The results of this planning grant will be a UM1 application to conduct the clinical trial that incorporates all of the developed materials and that will be ready for implementation. The long-term objectives are to change the trajectory of lupus management by targeting early events that can be modulated to prevent damage and improve outcomes.

Public Health Relevance

This project will plan a clinical trial to test whether treatment of patients at risk for lupus can slow progression of disease. The proposed trial will use hydroxychloroquine, which is an approved drug for the treatment for lupus. Effects on clinical progression of symptoms and changes in the immune response will be measured.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Clinical Planning Grant Cooperative Agreement (U34)
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Special Emphasis Panel (AMSC)
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Witter, James
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Pennsylvania State University
Internal Medicine/Medicine
Schools of Medicine
United States
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Karp, David R; Chong, Benjamin F; James, Judith A et al. (2018) Mock Recruitment for the Study of Antimalarials in Incomplete Lupus Erythematosus Trial. Arthritis Care Res (Hoboken) :
Aberle, Teresa; Bourn, Rebecka L; Chen, Hua et al. (2017) Use of SLICC criteria in a large, diverse lupus registry enables SLE classification of a subset of ACR-designated subjects with incomplete lupus. Lupus Sci Med 4:e000176
Munroe, Melissa E; Young, Kendra A; Kamen, Diane L et al. (2017) Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features. Arthritis Rheumatol 69:630-642
Munroe, Melissa E; Pezant, Nathan; Brown, Michael A et al. (2017) Association of IFIH1 and pro-inflammatory mediators: Potential new clues in SLE-associated pathogenesis. PLoS One 12:e0171193
Olsen, Nancy J; McAloose, Carl; Carter, Jamie et al. (2016) Clinical and Immunologic Profiles in Incomplete Lupus Erythematosus and Improvement with Hydroxychloroquine Treatment. Autoimmune Dis 2016:8791629