# Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE)

> **NIH NIH U01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2022 · $934,842

## Abstract

Project Summary/Abstract
Systemic lupus erythematosus (SLE) causes major organ damage and shortens lifespan in relatively young
persons. Early diagnosis and treatment are essential to improving outcomes for SLE patients. However,
evidenced-based approaches to early treatment interventions and the appropriate target population for these
interventions are not available. We propose that individuals who have positivity for antinuclear antibodies
(ANAs) and who also exhibit some of the other features that are used to classify SLE, are at high risk of
progressing to the full systemic form of this disease. These individuals, who have significant levels of ANA
with 1 or 2 additional items from the lupus classification criteria, are considered to have incomplete lupus
erythematosus or ILE. We propose to treat ILE patients with hydroxychloroquine (HCQ) in the “Study of Anti-
Malarials in Incomplete Lupus Erythematosus” or SMILE trial. The primary objective is to determine whether
HCQ treatment can prevent acquisition of additional clinical and immunologic features that define SLE.
The major secondary objectives are to determine whether HCQ treatment: (1) lessens lupus disease activity as
measured by standard scoring indices; (2) improves patient reported outcomes (3) prevents accumulation of
immunologic abnormalities including autoantibodies and cytokines and (4) has an acceptable toxicity profile.
The specific aims of this proposal are:
1. To carry out a double-blind, placebo-controlled, multicenter, randomized trial of HCQ vs. placebo in patients
with ILE. The study tests the hypothesis that early use of HCQ can modify disease features so that
accumulation of abnormalities leading to a classification of SLE can be significantly slowed.
2. To determine effects of HCQ on disease activity and patient-reported outcomes in patients with ILE.
3. To characterize the immunologic profile of HCQ in ILE-treated patients. Autoantibodies, cytokines and
chemokines will be measured on multiplex arrays for developing insights into underlying mechanisms.
4. To quantitatively assess the incidence of ophthalmologic toxicity in HCQ-treated ILE patients. All enrolled
patients will have standardized ophthalmologic examinations before and after study treatment.
Recommendations for use and monitoring in this patient population will be developed.
The SMILE trial will determine whether or not HCQ should be given to ILE patients, will provide insights into
the appropriate target population, and will propose candidate biomarkers to guide treatment decisions. While
not part of the Precision Medicine Initiative®, SMILE is consistent with its goals. It will be the first step towards
testing the feasibility of disease prevention studies in SLE and will accumulate biological samples in a
repository that will be available to the lupus research community for further in-depth mechanistic studies.

## Key facts

- **NIH application ID:** 10348096
- **Project number:** 5U01AR071077-05
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** DAVID R KARP
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $934,842
- **Award type:** 5
- **Project period:** 2017-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348096

## Citation

> US National Institutes of Health, RePORTER application 10348096, Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE) (5U01AR071077-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10348096. Licensed CC0.

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