American College of Rheumatology Annual Meeting

American College of Rheumatology Annual Meeting

Issue: December 2018
October 29, 2018
3 min read

Experts Debate Hydroxychloroquine Dosing Guidelines in Lupus

Issue: December 2018
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Michelle Petri

CHICAGO — Hydroxychloroquine has many indications, including systemic lupus erythematosus. In this setting, it has been shown to reduce flares, prevent organ damage, reduce cardiovascular risks, and protect against diabetes. However, recommendations released in 2016 by the American Academy of Ophthalmology emphasize the risk for retinopathy and suggest the dose be limited to 5 mg/kg of body weight.

The guidelines, which also include recommendations for screening, have left rheumatologists with questions regarding the proper dose in this patient population.

Here at the ACR/ARHP Annual Meeting, James T. Rosenbaum, MD, chair of division of arthritis and rheumatic diseases at Oregon Health and Science University and chair of ophthalmology at the Legacy Devers Eye Institute, and Michelle Petri, MD, MPH, professor of medicine at the Johns Hopkins University School of Medicine, director of the Hopkins Lupus Cohort, and co-director of the Hopkins Lupus Pregnancy Center, argued for and against the appropriateness of the guidelines in the treatment of lupus patients.

Recommendations released in 2016 by the American Academy of Ophthalmology for hydroxychloroquine emphasize the risk for retinopathy and suggest the dose be limited to 5 mg/kg of body weight.
Source: Shutterstock

Guidelines are appropriate

Rosenbaum argued that hydroxychloroquine is a safe and valuable drug, if monitored properly. He explained that the first guidelines issued by the American Academy of Ophthalmology in 2002, which recommended the use of an Amsler grid, were created in part to be less restrictive than the PDR for an eye exam every 3 months and recommended a dosage of 6.5 mg/kg per day. In 2016, a revised version of the guidelines recommended a maximum dose of 5 mg/kg based on actual weight, with an examination at baseline and repeat screening — via optical coherence tomography (OCT) and visual field tests — annually beginning at 5 years.

The guidelines are based on data, Rosenbaum said, and hydroxychloroquine toxicity has been studied for quite some time. In 2014, however, a “major” study published in JAMA Ophthalmology demonstrated that among patients treated with hydroxychloroquine for at least 5 years, the prevalence of retinal toxicity was three times higher than previously reported, with individual risks dependent upon dosage and duration of use. According to the study, “prevalence can exceed 50% with use above 5 mg/kg and with duration beyond 20 years.”

The guidelines have been validated in numerous studies, Rosenbaum said, citing data on additional toxicities associated with hydroxychloroquine, including cardiac toxicity, rashes, myopathy, hearing loss and others.

“Antimalarials are a valuable part of our therapeutic armamentarium and they have a very low rate of toxicity, if only we follow the appropriate guidelines,” Rosenbaum concluded.


Guidelines are not appropriate

According to Petri, the guidelines, which did not include input from rheumatologists, have instilled fear in lupus patients that could be affecting medication adherence.

“Twenty-nine percent of adolescents and young adults [with SLE] are nonadherent with their hydroxychloroquine, and of course they often have the worst lupus,” Petri said during her argument. “[We] always think that as the patient gets to know us and we get to know them, that adherence is going to improve, and this is an awful conclusion, isn’t it? That adherence worsens over the first year.”

Petri provided a personal anecdote about a patient who returned from a routine eye exam to inform her that the ophthalmologist lowered her dose of hydroxychloroquine because she was at risk for going blind. At this point, Petri explained, having a balanced conversation with the patient is very difficult.

“I can’t get the patient to be adherent again, and I can’t have a discussion about why the patient needs a higher dose,” she said. “It can’t be ‘one rule fits all’ in lupus — lupus is a disease where there’s still a lot of art and probably not enough science.”

Regarding dose, Petri said she still follows the 2002 guidelines and uses up to 6.5 mg/kg, but does not exceed 400 mg. She reduces the dose for elderly patients and those with renal insufficiency or renal failure, and she believes in the clinical benefit of monitoring hydroxychloroquine blood levels.

One point both Rosenbaum and Petri both agreed on was the importance of following the screening and follow-up guidelines.

“I don’t want to throw the baby out with bath water. I think all those studies of OCT are really important,” Petri said. “New technology is our friend; it’s how we’ll pick up retinopathy before it’s a long-term problem for the patient. ... I say, ‘no harm no foul.’ Let’s all obey these rules, let’s all insist on the OCT because you know most of our patients aren’t getting it.” – by Stacey L. Adams

Disclosure: Petri and Rosenbaum report no relevant financial disclosures.

Reference :

Petri M. The guidelines are not appropriate.

Rosenbaum J. The guidelines are appropriate. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.