Abstract
BackgroundOnset of systemic lupus erythematosus (SLE) is preceded by a preclinical phase characterized by expression of autoantibodies and nonspecific clinical symptoms. Hydroxychloroquine is a treatment for lupus that is widely used based on longstanding experience and a very good safety profile. Existing data suggest that treatment with hydroxychloroquine may postpone the onset of disease. However, prospective studies that prove and quantify the efficacy of hydroxychloroquine in the preclinical phase of lupus have not been done. This study will test the hypothesis that early hydroxychloroquine use can prevent accumulation of clinical abnormalities and modify immune responses that define SLE.MethodsA randomized, double-blind, placebo-controlled trial of hydroxychloroquine vs placebo will be conducted. Participants will have incomplete lupus erythematosus as defined by the presence of antinuclear antibody (ANA) positivity at a titer of 1:80 or greater, as well as one or two additional criteria from the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. The age range will be 15–45 years and the treatment phase will be 96 weeks. The primary endpoint will be the increase in the number of features of SLE defined by the 2012 SLICC classification schema. Secondary outcomes will include the proportion of participants who transition to a classification of SLE as defined by SLICC criteria.DiscussionA major challenge for improving therapies in patients with SLE is early detection of disease. The ANA test that is widely used to screen for SLE has low specificity and interpretation of its significance is challenging. The Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE) trial will provide insights into the appropriate target population for intervention, and will assess whether hydroxychloroquine can slow progression as measured by the accumulation of criteria. Ophthalmologic safety in this population will be assessed. The study will investigate candidate biomarkers that will guide treatment decisions and will accumulate a specimen biobank that will be available to the lupus research community for further in-depth mechanistic studies. This trial is a first step toward testing the feasibility of disease prevention strategies in SLE.Trial registrationClinicalTrials.gov, NCT 03030118. Registered on 24 January 2017.
Highlights
Onset of systemic lupus erythematosus (SLE) is preceded by a preclinical phase characterized by expression of autoantibodies and nonspecific clinical symptoms
Evaluation of outcomes The primary outcome is the increase in the number of clinical and/or laboratory features of SLE defined by the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria between week 4 and week 100
Secondary outcomes include the proportion of participants who transition to a classification of SLE according to the 2012 SLICC criteria and the 1997 American College of Rheumatology (ACR) criteria
Summary
Onset of systemic lupus erythematosus (SLE) is preceded by a preclinical phase characterized by expression of autoantibodies and nonspecific clinical symptoms. Systemic lupus erythematosus (SLE) is an autoimmune disease that causes major organ damage and shortens the lifespan. It has a disproportionate impact on young people, especially women. Morbidity and mortality in this largely young population are unacceptably high This is in part because many patients present at a stage when organ damage is already present. The finding that other autoantibodies more specific for SLE are present years prior to onset of clinical symptoms has suggested it is possible to identify early at-risk patients [3]. Blood profiling, including not just autoantibodies and cytokines and expressed genes, may be useful for identification of those who are at sufficiently high risk to justify therapeutic intervention [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
