A Phase III, Randomized, Double-Blind Placebo-Controlled, Non-Inferiority, Multi-Center Study of the Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease (SHIELD)
IRB Number: 2023-0408
January 31, 2025
Institutional Review Board, Hospital for Special Surgery
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Principal Investigator
Co-Investigators
Lisa R. Sammaritano, MD
Sarah B. Lieber, MD, MS
JoAnn Vega
Haley S. Slosberg
Summary
The purpose of this trial is to address the safety of withdrawal of hydroxychloroquine (HCQ) in patients with stable/quiescent SLE who are ≥60 years old. HCQ is a medication that is very effective in reducing lupus symptoms and disease activity. Despite a track record of safety with regard to infection compared to traditional immunosuppressive agents, HCQ confers an escalating risk of retinal toxicity with continued use. It is necessary to accurately weigh the risk of accumulating ocular exposure from HCQ versus the risk of SLE disease flare in a population that may have less active disease.
The study will enroll patients who fulfill classification criteria for SLE, are ≥60 years of age, are currently taking at least 200 mg HCQ daily for at least 7 years and have stable/quiescent disease, as defined below. 330 participants are expected to be enrolled across 8 sites over five years (41 participants per site).
Patients will be randomized to either the placebo or active arm and followed every 2 months for one year to assess disease activity and flares using validated disease activity and flare instruments in the context of serologic, cytokine and transcriptomic profiling. Patients will receive a ninety-day supply of investigational product (either active hydroxychloroquine or placebo) matching their stable dosage at their screening visit upon enrollment and randomization, at 2 months, 4 months, 6 months, 8 months, and 10 months. Since this is a double blind, placebo-controlled study, neither the patient nor the study team will be aware of the arm to which the patient is randomized.
Inclusion/Exclusion Criteria
Inclusion Criteria
1. Age ≥ 60 years at time of enrollment
2. Normal OCT and VF assessment within 6 months of screening visit
3. Have established SLE (≥ 4 ACR criteria or SLICC criteria or ≥ 10 points by EULAR criteria, SLE diagnosed at least seven years ago)
4. Stable disease at screening visit by attaining DORIS remission (meeting all criteria listed below) and not on any immunosuppressants.
a. Criterion 1: Clinical SLEDAI= 0
b. Criterion 2: SELENA-SLEDAI PGA ≤ 0.5 (on a scale from 0-3, where 0 is no disease activity and 3 is maximum disease activity)
c. Criterion 3: Current prednisolone (or equivalent corticosteroid) dose ≤ 5 mg daily
5. No moderate or severe flares one year prior to screening
6. Taking ≥ 200 HCQ daily for ≥ 7 years
Exclusion Criteria
1. Any patient that does not attain stable disease status by DORIS
2. Ophthalmologic evidence of retinopathy (these patients would be advised to discontinue HCQ and therefore unethical to randomize for this study)
3. Clinical SLEDAI > 0
4. Taking > 5 mg/day prednisone
5. Taking any immunosuppressive drugs or biological agents (including: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, cyclosporine, cyclophosphamide, tacrolimus, rituximab, and belimumab)
6. Any reason the treating rheumatologist is concerned about ongoing activity not captured by SLEDAI
7. HCQ level < 100 ng/ml as this would support noncompliance and less reliance on HCQ to control activity
Contact Information
Haley Slosberg, Research Coordinator
slosbergh@hss.edu
212.774.2223
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