Lower Hydroxychloroquine Dosing is Less Effective in Preventing Lupus Flares


April Jorge, MD

April Jorge, MD, an investigator in the Department of Rheumatology, Allergy, and 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 according to ophthalmic guidelines and the risk of systemic lupus erythematosus flares.

What question did you want to answer with this study?

Hydroxychloroquine prevents flare-ups of systemic lupus erythematosus (SLE) 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-related risk led to ophthalmic guidelines in 2016 and subsequent rheumatological recommendations to avoid prescribing doses of hydroxychloroquine in excess of 5 mg/kg per day. However, it was not previously known whether lower doses would lead to more lupus flare-ups. Therefore, with this study, we assessed the association of this dose threshold with the risk of lupus flares.

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What is two or three key takings?

We found that patients with lupus who received a lower dose of hydroxychloroquine—according to current ophthalmic guidelines—had a higher risk of lupus flare-ups than those who took a higher dose of the drug.

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

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What were your conclusions?

Hydroxychloroquine dosages below 5 mg/kg/day are less effective than higher dosages in preventing flare-ups of lupus.

Individual risks and benefits of hydroxychloroquine should be considered when determining the appropriate dose of the drug. Some patients may require higher dosages than current guidelines would allow.

Cited paper:

Jorge AM, Mancini C, Zhou B, Ho G, Zhang Y, Costenbader K, & Choi HK (2022). Hydroxychloroquine dose according to ophthalmic guidelines and the risk of systemic lupus erythematosus flares. JAMA, 10.1001/jama.2022.13591. Online Advance Release. https://doi.org/10.1001/jama.2022.13591

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About Massachusetts General Hospital

Founded in 1811, Massachusetts General Hospital is Harvard Medical School’s original and largest teaching hospital. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations exceeding $1 billion and includes more than 9,500 researchers working in more than 30 institutes, centers and departments. In July 2022, Mass General was ranked #8 on US News & World Report’s list of “America’s Best Hospitals.” MGH is a charter member of the Mass General Brigham Health System.



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