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.”
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JAMA 2022; doi:10.1001/jama.2022.13591