Reducing risk of HCQ retinopathy comes at a cost

3 minute read


Lupus patients meeting ophthalmology dosage guidelines for hydroxychloroquine were at increased risk of flares.


A retrospective case-crossover study investigating flares in lupus patients taking hydroxychloroquine has linked dosage levels consistent with recommended ophthalmological guidelines with higher risk of flare.

Patients taking 5mg/kg/day or less HCQ were around twice as likely to experience a flare as those taking more than 5mg/kg/day, and around six times as likely to have a moderate or severe flare.

“This study highlights the need to consider individualized risks and benefits in choosing the optimal dose of hydroxychloroquine, an important medication in lupus care,” wrote the authors in JAMA.

The study was conducted in the context of current ophthalmology and rheumatology guidelines which recommend avoiding doses higher than 5mg/kg/day to reduce the risk of retinopathy in long-term HCQ users.

The records of lupus patients from Massachusetts General Hospital who’d used HCQ between 2016 (when the ophthalmology guidelines were introduced) and 2020 were included in the study.

Patients were used as their own controls, with mean weight-based dose of HCQ in the 6 months prior to a flare compared with the 6 months prior to a visit with no flare. Doses were categorised as less than or equal to 5mg/kg/day or greater than 5mg/kg/day.

Of the 342 patients included, about half (49%) had at least one flare during the study period. The odds ratio (OR) for any lupus flare associated with HCQ 5mg/kg/day or less compared with more than 5mg/kg/day was 1.98 (95% CI, 1.03-3.79), adjusted for glucocorticoid use, immunosuppressant use and disease activity. The adjusted OR for moderate or severe flares was 6.04 (95% CI, 1.17-21.30).

Limitations of the study include the retrospective study design, the absence of data on medication adherence and the use of an academic medical centre cohort.

After presenting some of the data at ACR Convergence 2021, lead author Dr April Jorge said that given the higher doses do have a higher risk retinopathy, there probably isn’t one safe and effective dose across the board.

“It’s going to come down to individual patient decision making and balancing the risks and benefits. I think there might be some patients whose lupus is active that really do need a higher dose of hydroxychloroquine, at least for some period of time. Just monitor them closely, and keep in mind the long-term exposure of this medication when you’re making that decision.

“And definitely discuss the risks and benefits with the patient,” Dr Jorge added.

JAMA 2022, online 16 September

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