Research Spotlight: Lower Hydroxychloroquine Dosing is Less Effective in Preventing Lupus Flares

April Jorge, MD, a Physician-Investigator in the Division of Rheumatology, Allergy & Immunology at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School, is the lead author of a research letter in JAMA, Hydroxychloroquine Dose per Ophthalmology Guidelines and the Risk of Systemic Lupus Erythematosus Flares.

What was the question you set out to answer with this study?

Hydroxychloroquine prevents systemic lupus erythematosus (SLE) flares and is recommended for all patients with SLE.

However, its long-term toxicity includes retinopathy, particularly at doses greater than 5 mg/kg per day. This dose-dependent risk led to 2016 ophthalmology guidelines and subsequent rheumatology recommendations to avoid prescribing hydroxychloroquine doses greater than 5 mg/kg per day. However, it has not been previously known whether lower dosing would lead to more lupus flares. Therefore, with this study, we assessed the association of this dose threshold on the risk of lupus flares.

What are two or three key takeaways?

We found that when patients with lupus received lower dosing of hydroxychloroquine—in  accordance with current ophthalmology guidelines—they had a higher risk of lupus flares than when they were taking a higher dose of the medication.

Using <5 mg/kg/day dosing was associated with an increased risk of all lupus flares and of moderate/severe lupus flares.

What were your conclusions?

Hydroxychloroquine dosing under 5 mg/kg/day is less effective in preventing lupus flares than higher dosing.

Individualized risks and benefits of hydroxychloroquine should be considered in determining the appropriate dose of the medication. Some patients may need higher dosing than current guidelines would allow.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.