# Stopping Hydroxychloroquine In Elderly Lupus Disease (SHIELD)

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $1,308,540

## Abstract

This U01 application SHIELD (Stopping Hydroxychloroquine (HCQ) In Elderly Lupus Disease) follows
completion of an R34 and is driven by the exigency to establish evidence-based protocols for the management
of aging lupus patients, a topic that has received minimal attention. 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. 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. The decision to discontinue HCQ is difficult; however clinical equipoise should guide this consideration
especially in patients who have been stable and on the medication for years. As the longevity of lupus patients
improves, which may increase comorbidities that affect HCQ clearance (e.g., renal insufficiency), the ratio of
efficacy to toxicity is expected to decrease. That disease activity may wane in the aging population drives the
ratio down even further. The purpose of this U01 is to conduct a Phase III, randomized, double-blind placebo
controlled, multi-center, non-inferiority clinical trial 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. The population under study will be 330 patients who fulfill at least one of the classification
criteria (ACR, SLICC, EULAR/SLICC) for SLE, are ≥60yrs, are currently taking at least 200 mg HCQ daily for at
least 7yrs and have stable disease. 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. Subjects will be recruited from NYU (Peter
Izmirly, Jill Buyon), Albert Einstein (Anna Broder), HSS (Jane Salmon), Columbia (Anca Askanase), OMRF (Joan
Merrill), Penn State (Nancy Olsen), and UCLA (Maureen McMahon). The primary outcome will be the occurrence
of a moderate/severe flare during follow-up. Sample size is based on the projection of a 13% moderate/severe
flare rate in patients remaining on HCQ and a non-inferiority margin equal to a 10% absolute difference in rates
between groups. The trial infrastructure has been established in compliance with NIH guidelines and completion
of the following deliverables from the awarded R34: model recruitment supported by an sIRB with all sites; study
protocol with inclusion of biomarker studies and comprehensive statistical analysis plan; manual of operating
procedures; electronic data capture system; data management plan; acquisition of study drugs; and training of
support staff. It is anticipat...

## Key facts

- **NIH application ID:** 10908999
- **Project number:** 5R01AR082149-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jill P Buyon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,308,540
- **Award type:** 5
- **Project period:** 2023-08-17 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908999

## Citation

> US National Institutes of Health, RePORTER application 10908999, Stopping Hydroxychloroquine In Elderly Lupus Disease (SHIELD) (5R01AR082149-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10908999. Licensed CC0.

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