Stopping Hydroxychloroquine for Lupus

(SHIELD Trial)

Recruiting at 9 trial locations

Overseen by Jill Buyon, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NYU Langone Health

Must be taking: Hydroxychloroquine

Must not be taking: Immunosuppressants, Biological agents

Disqualifiers: Retinopathy, Dementia, Cognitive impairment, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if older lupus patients can safely stop taking Hydroxychloroquine, a drug that reduces lupus symptoms but can harm the eyes over time. The study focuses on patients aged 60 and above who have stable disease. Researchers will monitor these patients for an extended period to see if their condition remains stable without the drug.

Do I need to stop my current medications for this trial?

The trial specifically focuses on stopping hydroxychloroquine (HCQ) for lupus patients. Participants must not be on any immunosuppressive drugs or biological agents, and they should have a stable disease status without moderate or severe flares in the past year.

What data supports the effectiveness of the drug hydroxychloroquine for lupus?

Research indicates that hydroxychloroquine helps prevent disease flares (sudden worsening of symptoms) and reduces damage in patients with lupus. It is also associated with improved survival rates and is recommended for all lupus patients due to its efficacy and safety. ^{1 2 3 4 5}

Is hydroxychloroquine generally safe for humans?

Hydroxychloroquine is generally well-tolerated, but it can cause serious side effects like retinal toxicity (eye damage) and cardiotoxicity (heart damage). Common side effects include skin rashes, stomach issues, and headaches, so regular monitoring by a doctor is important. ^{6 7 8 9 10}

How does the drug hydroxychloroquine differ from other treatments for lupus?

Hydroxychloroquine is unique because it not only helps manage lupus symptoms like joint pain and skin rashes but also reduces the risk of heart disease by lowering cholesterol and preventing blood clots. It is often used as a long-term treatment to prevent lupus flares and reduce the need for steroids, which can have more severe side effects. ^{4 5 9 11 12}

Research Team

Peter Izmirly

Principal Investigator

NYU Langone Health

Jill Buyon, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for stable/quiescent elderly patients (60+ years) with systemic lupus erythematosus who've been on Hydroxychloroquine (≥200mg daily) for at least 7 years. They must have no recent severe flares, be able to take oral meds, and show no retinal damage. Those on high-dose steroids or immunosuppressants are excluded.

Inclusion Criteria

I am 60 years old or older.

Provision of signed and dated informed consent form

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

Exclusion Criteria

My disease has not stabilized according to DORIS.

My HCQ level is below 100 ng/ml, indicating I haven't been relying on it.

Ophthalmologic evidence of retinopathy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Hydroxychloroquine or a matching placebo every 2 months for one year to assess disease activity and flares

12 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Hydroxychloroquine (Anti-malarial drug)
• Placebo (Drug)

Trial Overview The study tests the safety of stopping Hydroxychloroquine in older adults with inactive lupus by comparing it against a placebo. Participants will be randomly assigned to either continue HCQ or switch to a placebo and monitored bi-monthly for a year to track disease activity.

Participant Groups

Group I: Hydroxychloroquine (HCQ) Experimental Treatment 1 Intervention

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.

Group II: HCQ-Matching Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Dr. Alec C. Kimmelman

NYU Langone Health

Chief Executive Officer

MD and PhD from Mount Sinai School of Medicine

Dr. Nicole M. Adler

NYU Langone Health

Chief Medical Officer since 2023

MD

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

Findings from Research

In a six-month study involving 47 patients with stable systemic lupus erythematosus, those who continued taking hydroxychloroquine had a significantly lower risk of experiencing flare-ups compared to those who received a placebo, with a relative risk of 2.5 times higher for the placebo group.

Patients on placebo not only had more flare-ups but also experienced a shorter time to flare-up, and the risk of severe disease exacerbations was 6.1 times higher in the placebo group, indicating that maintaining hydroxychloroquine treatment is beneficial for preventing disease worsening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. [2022]

In a study of 539 systemic lupus erythematosus (SLE) patients followed for a median of 19 years, hydroxychloroquine (HCQ) was initiated by 96.7% of patients, demonstrating its widespread use due to its efficacy and safety profile.

The main reason for discontinuing HCQ was drug toxicity, particularly macular toxicity, affecting 18.6% of patients, highlighting the importance of monitoring for adverse effects in long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why lupus patients discontinue antimalarials in real life: A 50 years-experience from a reference centre. Araújo, O., Hernández-Rodríguez, J., Pelegrín, L., et al.[2022]

In a study of 608 patients with systemic lupus erythematosus (SLE), hydroxychloroquine was found to significantly improve survival rates, with a protective effect indicated by an odds ratio of 0.128 when used alone.

The protective effect of hydroxychloroquine on survival remained significant even after adjusting for confounding factors, suggesting it is a crucial treatment for enhancing longevity in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Alarcón, GS., McGwin, G., Bertoli, AM., et al.[2022]

In a study of 509 patients with systemic lupus erythematosus (SLE), those who discontinued hydroxychloroquine (HCQ) after less than one year were significantly more likely to experience disease flares compared to those who continued treatment for over a year (13.1% vs 5.7%).

The research indicates that longer duration of HCQ use is associated with better disease control, suggesting that continued treatment is crucial for managing SLE and reducing the risk of flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Systemic Lupus Erythematosus in Patients who Discontinue Hydroxychloroquine. Aouhab, Z., Hong, H., Felicelli, C., et al.[2022]

In a study of 224 patients with systemic lupus erythematosus (SLE), 70% used antimalarials, primarily hydroxychloroquine (HCQ), with an average treatment duration of 6.9 years, indicating long-term use is common.

While HCQ is generally well tolerated, there is a small risk of serious side effects, including retinopathy (0.95 cases per 1000 patient-years), highlighting the importance of regular ophthalmologic monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discontinuation of antimalarial drugs in systemic lupus erythematosus. Wang, C., Fortin, PR., Li, Y., et al.[2013]

A 71-year-old woman experienced retinal toxicity after taking hydroxychloroquine for 5 years, highlighting the risk of ocular side effects, particularly toxic maculopathy, associated with this medication.

The only effective treatment for hydroxychloroquine toxicity is to discontinue the drug, but the toxic effects may continue to progress due to the slow clearance of the medication, emphasizing the importance of regular eye examinations before and during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal toxicity secondary to Plaquenil therapy. Hanna, B., Holdeman, NR., Tang, RA., et al.[2016]

Hydroxychloroquine is an effective and well-tolerated drug for treating systemic lupus erythematosus and lupus nephritis, with mechanisms that include inhibiting inflammation and modulating immune responses.

While it shows promise for treating other kidney diseases and reducing cardiovascular risks, clinicians must monitor for potential side effects like retinal toxicity and cardiomyopathy, and blood level monitoring could help manage these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxychloroquine in nephrology: current status and future directions. Rao, IR., Kolakemar, A., Shenoy, SV., et al.[2023]

Hydroxychloroquine sulfate (HCQ) is used to treat autoimmune disorders but can cause severe retinal toxicity, including irreversible maculopathy, necessitating careful monitoring and potential discontinuation of therapy.

It is crucial for healthcare providers, including rheumatologists and ophthalmologists, to be aware of the risks associated with HCQ and to implement screening protocols to minimize the incidence of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. Geamănu Pancă, A., Popa-Cherecheanu, A., Marinescu, B., et al.[2022]

Hydroxychloroquine (HCQ) and chloroquine (CQ) are effective in treating systemic lupus erythematosus, improving symptoms like joint pain, fatigue, and skin rashes, while also reducing the need for steroids and lowering the risk of cardiovascular disease.

Although there are potential side effects, particularly related to retinal damage, these are rare and manageable, making anti-malarials a safe long-term treatment option for many lupus patients. Regular ophthalmologist check-ups are recommended to monitor for any issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current view on chloroquine derivative treatment from rheumatologist perspective and possible ocular side effects]. Pawlak-Buś, K., Gaca-Wysocka, M., Grzybowski, A., et al.[2016]

Hydroxychloroquine, commonly used for rheumatological disorders, has been linked to a variety of adverse effects, particularly in women over 50, with skin rashes being the most common issue occurring within 4 weeks of treatment.

More severe adverse events, although rare, include serious skin reactions like Stevens-Johnson syndrome and systemic issues such as cardiotoxicity and retinopathy, highlighting the importance of monitoring patients on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events. Gisondi, P., Piaserico, S., Bordin, C., et al.[2022]

4-aminoquinoline radical drugs, like hydroxychloroquine, are effective in managing systemic lupus erythematosus (SLE) and rheumatoid arthritis by interfering with antigen processing and reducing inflammation, which is beneficial for patients with these conditions.

Despite concerns about their use during pregnancy due to potential fetal risks, it is suggested that these drugs should not be discontinued in pregnant patients with lupus to prevent disease flares that could negatively impact pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimalarial drugs in systemic lupus erythematosus: use in pregnancy. Borden, MB., Parke, AL.[2019]

The combination of hydroxychloroquine (HCQ) and quinacrine (Qn) at a dosage of 100 mg/qd significantly improved various lupus skin lesions in 34 patients, with notable improvements in discoid lupus erythematosus and acute malar rash.

While the treatment was generally well tolerated, some patients experienced side effects, including skin discoloration and, in rare cases, more severe reactions like hepatitis, particularly in those with preexisting conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of lupus skin involvement with quinacrine and hydroxychloroquine. Cavazzana, I., Sala, R., Bazzani, C., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Why lupus patients discontinue antimalarials in real life: A 50 years-experience from a reference centre. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Systemic Lupus Erythematosus in Patients who Discontinue Hydroxychloroquine. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Discontinuation of antimalarial drugs in systemic lupus erythematosus. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Retinal toxicity secondary to Plaquenil therapy. [2016]

7. Italy pubmed.ncbi.nlm.nih.gov

Hydroxychloroquine in nephrology: current status and future directions. [2023]

8. Romania pubmed.ncbi.nlm.nih.gov

Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. [2022]

9. Poland pubmed.ncbi.nlm.nih.gov

[Current view on chloroquine derivative treatment from rheumatologist perspective and possible ocular side effects]. [2016]

10. Italy pubmed.ncbi.nlm.nih.gov

The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Antimalarial drugs in systemic lupus erythematosus: use in pregnancy. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Treatment of lupus skin involvement with quinacrine and hydroxychloroquine. [2013]