SAN FRANCISCO – Hydroxychloroquine (Plaquenil) dosing based on actual body weight – instead of ideal weight – is appropriate for patients with systemic lupus erythematosus (SLE), according to a review of 686 lupus patients at Johns Hopkins University in Baltimore.
Most were dosed by actual weight, 6.5 mg/kg up to a maximum of 400 mg/day. Patients with renal insufficiency were dosed at 200 mg daily, and those on hemodialysis received 200 mg after their sessions.
In their analysis, Hopkins researchers calculated that ideal and actual body weight dosing yielded statistically equivalent hydroxychloroquine blood levels. “This was reassuring. The take-home message is dosing based on actual weight” – up to 400 mg/day – “is appropriate,” said lead investigator Dr. Laura Durcan, now a rheumatology fellow at the University of Washington in Seattle.
M. Alexander Otto/Frontline Medical News
Dr. Laura Durcan
Rheumatologists generally opt for weight-based dosing, but ophthalmologists prefer to use ideal body weight to prevent overdoses in obese patients at an increased risk for retinopathy. The Hopkins team seems to have found a workable middle ground – weight-based dosing up to a maximum of 400 mg/day, which is considered safe in a lean person of about 136 pounds.
Three months after being prescribed hydroxychloroquine, however, just 56% of the patients were at a therapeutic level of 500 ng/mL or more. The rest were either subtherapeutic at 15-500 ng/mL or had no detectable hydroxychloroquine in their blood.
The problem was adherence. “We were horrified” at “how poorly compliant patients were in a cohort that is very well educated about the benefits of medication, and surprised by how few of them were taking their pills as prescribed,” Dr. Durcan said at the annual meeting of the American College of Rheumatology.
Even so, it’s well known that drug adherence is a problem with chronic disease, so “I think our numbers would be similar in any lupus cohort,” she said.
The researchers fixed the problem by insisting patients activate their Hopkins electronic health record portal, so they could check their blood work. If their numbers were low, they saw a reminder on their results page to take their pills every day, and the record system added a note to their chart to bring up adherence during the next office visit.
That’s all it took for most patients. By about their third office visit, 80% of patients were in the therapeutic range. “If you have a measurable outcome, you can significantly impact patient adherence,” Dr. Durcan said.
There was a trend towards higher disease activity with lower drug levels. The 13% of patients with undetectable levels at their first hydroxychloroquine checkup had a mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of 2.92, and the 31% who were subtherapeutic had a mean SLEDAI of 2.36. The 56% of patients in the therapeutic range had a mean SLEDAI of 2.20 (P = .04 for trend).
Those differences probably didn’t mean much clinically, but “it’s important to note that the impacts of therapy go beyond the immediate impact on disease activity,” Dr. Durcan said.
Over 90% of the subjects were women, and most were over 30 years old. The few men in the study were a bit more likely to have therapeutic levels of hydroxychloroquine 3 months after it was prescribed.
Hopkins uses in-house mass spectrometry to measure hydroxychloroquine concentrations in whole blood, believing it is more accurate and meaningful than the serum levels used elsewhere.
The investigators have no relevant disclosures. The work was funded by the National Institutes of Health.