Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease (SHIELD)

NYU Langone Health

Status and phase: Enrolling; Phase 3

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: Placebo; Drug: Hydroxychloroquine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05799378

23-00071

Details and patient eligibility

About

Hydroxychloroquine (HCQ) is a systemic lupus erythematosus (SLE) medication that has been very effective in reducing lupus disease activity and keeping patients stable with reduced symptoms. Despite a track record of safety with regard to infection compared to traditional immunosuppressive agents, the risk of HCQ retinal toxicity escalates with continued use. Evaluation using sensitive standard of care approaches suggests nearly a third of patients accrue retinal damage. Data are needed to accurately weigh the balance between accumulating ocular exposure of HCQ versus the risk of disease flare in a population that may have more inactive disease than younger patients. The purpose of this trial is to address the safety of withdrawal of HCQ in SLE patients =60 years old. The central hypothesis is that HCQ can be safely discontinued in stable/quiescent patients assessed by validated disease activity and flare instruments in the context of serologic, cytokine and transcriptomic profiling. 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.

Enrollment: 330 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Provision of signed and dated informed consent form

• Stated willingness to comply with all study procedures and availability for the duration of the study

• Age ≥ 60 years at time of enrollment

• Normal OCT and VF assessment within 6 months of screening visit

• Ability to take oral medication

• Have established SLE (≥ 4 ACR criteria or SLICC criteria or ≥ 10 points by EULAR criteria, SLE diagnosed at least seven years ago)

• Stable disease at screening visit by attaining DORIS remission (meeting all criterion listed below) and not on any immunosuppressants.

  • Criterion 1: Clinical SLEDAI= 0
  • 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)
  • Criterion 3: Current prednisolone (or equivalent corticosteroid) dose ≤ 5 mg daily

• No moderate or severe flares one year prior to screening

• Taking ≥ 200 HCQ daily for ≥ 7 years

Exclusion criteria

• Any patient that does not attain stable disease status by DORIS
• Ophthalmologic evidence of retinopathy (these patients would be advised to discontinue HCQ and therefore unethical to randomize for this study)
• Clinical SLEDAI > 0
• Taking > 5 mg/day prednisone
• Taking any immunosuppressive drugs or biological agents (including: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, cyclosporine, cyclophosphamide, tacrolimus, rituximab, and belimumab)
• Any reason the treating rheumatologist is concerned about ongoing activity not captured by SLEDAI
• HCQ level < 100 ng/ml as this would support noncompliance and less reliance on HCQ to control activity
• Patient unwilling or unable to comply with study procedures for any reason
• Any indications of potentially diminished capacity, such as a diagnosis of dementia or cognitive impairment (including, but not limited to stroke-related cognitive impairment)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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330 participants in 2 patient groups, including a placebo group

Hydroxychloroquine (HCQ)

Experimental group

Description:

Patients will receive a 90-day supply of HCQ at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ dose administered will match each patient's dosage of HCQ at enrollment.

Treatment:

Drug: Hydroxychloroquine

HCQ-Matching Placebo

Placebo Comparator group

Description:

Patients will receive a 90-day supply of HCQ-matching placebo at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ-matching placebo dose administered will match each patient's dosage of HCQ at enrollment.

Treatment:

Drug: Placebo