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29-09-2022 | Systemic lupus erythematosus | News

Reduced-dose hydroxychloroquine linked to higher flare risk in SLE

Author: Claire Barnard

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medwireNews: Research suggests that using a daily hydroxychloroquine dose of 5 mg/kg or lower, as recommended by ophthalmology guidelines, is associated with an increased risk for systemic lupus erythematosus (SLE) flares compared with higher doses.

Writing in a letter to JAMA, April Jorge (Massachusetts General Hospital, Boston, USA) and co-authors explain that the long-term toxicity of hydroxychloroquine “includes retinopathy, particularly at doses greater than 5 mg/kg per day.”

They add: “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, Jorge et al found that doses at or below this threshold were associated with a significant 1.98-fold increased risk for SLE flares relative to higher doses after adjustment for confounding factors, as well as a 6.04-fold increased risk for moderate or severe flares.

The case-crossover study included 168 hydroxychloroquine-treated individuals from Massachusetts General Hospital who experienced an SLE flare (according to the revised SELENA-SLEDAI flare index) in 2016–2020, with some patients experiencing more than one. Case periods were defined as the 6 months leading up to a flare, while control periods were defined as each 6-month period leading up to clinic visits with no flare. The mean weight-based hydroxychloroquine dose during each 6-month period was categorized as up to or greater than 5 mg/kg per day.

Of the 308 periods leading up to a flare, 57.5% occurred when patients were taking the lower hydroxychloroquine dose, while 42.5% occurred when they were on higher doses. The corresponding proportions for moderate or severe flares were 63.1% and 36.9%.

The researchers then modeled the estimated risk for SLE flare according to hydroxychloroquine dose, with the smoothed dose odds ratio curve indicating “an apparent threshold near 5 mg/kg per day.”

They say that “[t]ogether, these findings suggest reduced efficacy of lower hydroxychloroquine dosing for lupus disease activity, particularly around doses of 5mg/kg per day or less.”

And Jorge et al conclude: “This study highlights the need to consider individualized risks and benefits in choosing the optimal dose of hydroxychloroquine, an important medication in lupus care.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA 2022; doi:10.1001/jama.2022.13591


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