Stopping Hydroxychloroquine for Lupus

(SHIELD Trial)

Recruiting at 10 trial locations

Overseen By Mala Masson

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 months

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether it is safe for people with lupus to stop taking hydroxychloroquine (HCQ), a drug that helps manage the condition. Researchers aim to determine if stopping HCQ could cause lupus symptoms to return, especially since long-term use can harm the eyes. Participants will either continue taking HCQ or switch to a placebo to assess if their lupus remains controlled. This trial targets individuals aged 60 and older who have had stable lupus for at least one year without recent flare-ups. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to research that could change lupus treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that hydroxychloroquine (HCQ) is generally safe and well-tolerated for people with lupus. It has been used for many years to reduce lupus symptoms and maintain disease stability. Studies indicate that HCQ can lower disease activity by more than half for many patients.

However, long-term use of HCQ can lead to eye damage, known as retinal toxicity. About one-third of patients may experience some eye damage over time, prompting doctors to exercise caution when prescribing HCQ for extended periods.

Regarding safety, HCQ is usually recommended for most lupus patients, including those who are pregnant or breastfeeding. However, stopping HCQ before a year may increase the risk of lupus flares. One study found that discontinuing HCQ in stable lupus patients could raise the risk of disease flares by 2.5 times.

In summary, while HCQ is effective and mostly safe, it can cause eye issues with long-term use. Balancing the benefits of controlling lupus with the risk of eye damage is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the possibility of stopping hydroxychloroquine (HCQ) in patients with lupus, a condition traditionally managed with ongoing HCQ treatment. Current lupus treatments often involve long-term use of medications like HCQ, which can lead to side effects over time. This trial examines whether patients can maintain their health without continuous HCQ use, potentially reducing medication burden and side effects. If successful, this approach could transform how lupus is managed by personalizing treatment and minimizing unnecessary drug exposure.

What is the effectiveness track record for Hydroxychloroquine in treating lupus?

Studies have shown that hydroxychloroquine (HCQ) effectively reduces the symptoms of systemic lupus erythematosus (SLE). It helps prevent flare-ups and can decrease the need for long-term steroid use. Research indicates that patients with stable SLE who continue taking HCQ are less likely to experience flare-ups than those who stop. This trial will compare the effects of continuing HCQ with an HCQ-matching placebo to evaluate the impact of stopping the medication. Overall, HCQ offers proven benefits for managing SLE symptoms and controlling the disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Peter Izmirly

Principal Investigator

NYU Langone Health

Jill Buyon, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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

Provision of signed and dated informed consent form

I am 60 years old or older.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Hydroxychloroquine
• Placebo

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.

How Is the Trial Designed?

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.

Hydroxychloroquine is already approved in United States, European Union for the following indications:

Approved in United States as Plaquenil for:

• Malaria
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Approved in European Union as Plaquenil for:

• Malaria
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

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]

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]

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]

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]

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, 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8848057/

Hydroxychloroquine in systemic lupus erythematosus HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6857977/

Outcomes of Systemic Lupus Erythematosus in Patients who ... Previous randomized drug withdrawal–based studies demonstrated significant decreases in SLE flares in individuals taking HCQ compared with those taking a ...

3. lupus.org lupus.org/resources/drug-spotlight-on-hydroxychloroquine

Hydroxychloroquine (Plaquenil): Benefits, Side Effects, and ... In 1955 HCQ was shown to be effective for both systemic lupus and rheumatoid arthritis. (Wallace DJ, Hahn BH, eds. Dubois' Lupus Erythematosus. 1997:1117 ...

4. nejm.org nejm.org/doi/full/10.1056/NEJM199101173240303

A Randomized Study of the Effect of Withdrawing ... Patients with quiescent systemic lupus erythematosus who are taking hydroxychloroquine are less likely to have a clinical flare-up if they are ...

5. nature.com nature.com/articles/s41598-024-58463-3

An observational study to identify causative factors for not ... Hydroxychloroquine improves the disease activity and allows the reduction of the corticosteroid dose regardless of background treatment in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01551069

NCT01551069 | Multicenter Study Assessing the Efficacy & ... Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double-Blind, Randomized, Parallel-Group Trial. Arthritis ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S004901722200097X

Outcomes following antimalarial withdrawal in patients with ... One previous randomized controlled trial showed that withdrawal of hydroxychloroquine in patients with quiescent SLE resulted in a 2.5 times increased risk of ...