Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Description

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.

Conditions

Systemic Lupus Erythematosus

Study Overview

Study Details

Study overview

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.

A Phase III, Randomized, Double-Blind Placebo-Controlled, Non-Inferiority, Multi-Center Study of the Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Condition
Systemic Lupus Erythematosus
Intervention / Treatment

-

Contacts and Locations

Los Angeles

University of California, Los Angeles, Los Angeles, California, United States, 90095

Hackensack

Hackensack Meridian Health, Hackensack, New Jersey, United States, 07601

Bronx

Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, United States, 10461

New York

VA NY Harbor Healthcare System, New York, New York, United States, 10010

New York

NYC Health + Hospitals/Bellevue, New York, New York, United States, 10016

New York

NYU Langone Health, New York, New York, United States, 10016

New York

Hospital for Special Surgery, New York, New York, United States, 10021

New York

Columbia University Irving Medical Center/New York Presbyterian, New York, New York, United States, 10032

Oklahoma City

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States, 73104

Hershey

Penn State MS Hershey Medical Center, Hershey, Pennsylvania, United States, 17033

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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
  • * 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)

Ages Eligible for Study

60 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

NYU Langone Health,

Peter Izmirly, PRINCIPAL_INVESTIGATOR, NYU Langone Health

Jill Buyon, PRINCIPAL_INVESTIGATOR, NYU Langone Health

Study Record Dates

2029-06-30