– Routine office measurement of hydroxychloroquine blood levels in systemic lupus erythematosus (SLE) patients accomplishes two major objectives, Nathalie Costedoat-Chalumeau, MD, asserted at an international congress on systemic lupus erythematosus.

Dr. Nathalie Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University Bruce Jancin/MDedge News

Dr. Nathalie Costedoat-Chalumeau

First, measuring hydroxychloroquine levels identifies the surprisingly large number of individuals who are severely nonadherent to this cornerstone of lupus therapy despite its excellent benefit/risk ratio. Also, serial measurements coupled with brief counseling have been shown to boost poor adherence rates, noted Dr. Costedoat-Chalumeau, professor of rheumatology at Paris Descartes University.

Numerous studies have documented startlingly low adherence to hydroxychloroquine among SLE patients. Some of the same studies show prescribing physicians are often clueless as to their patients’ adherence or lack thereof.

Just how bad is the adherence problem? A recent study of 10,406 Medicaid patients with SLE who started on hydroxychloroquine showed that 85% of them were nonadherent as defined by pharmacy refill data, indicating insufficient medication on hand to cover a minimum of 80% of days during at least 1 year of follow-up.

In a novel finding, the investigators also broke down the Medicaid data month by month and identified four broad patterns of adherence/nonadherence. A total of 17% of patients were persistently adherent throughout the first year after the drug was dispensed. Another 36% were persistent nonadherers right from the get-go. A further 24% remained partially adherent, dropping down to a plateau of 30%-40% monthly adherence after the first couple of months and staying there. And 23% dropped steadily from roughly 50% adherence at month 3 to nearly total nonadherence from month 9 onward. Overall, adherence in the Medicaid cohort declined over the course of the first year (Semin Arthritis Rheum. 2018 Oct;48[2]:205-13).

Dr. Costedoat-Chalumeau was the lead investigator in a large French multicenter clinical trial known as the PLUS Study, which established that increasing the hydroxychloroquine daily dose to raise blood levels to a target of at least 1,000 ng/mL didn’t reduce the risk of flares (Ann Rheum Dis. 2013;72[11]:1786-92).

“So there is no reason to use blood drug measurements to adjust hydroxychloroquine daily dose or blood levels to prevent SLE flares. But drug levels teach us something regarding adherence,” she said.

Why routinely measuring hydroxychloroquine levels matters

Dr. Costedoat-Chalumeau and other investigators have shown that whole blood drug levels below 200 ng/mL indicate a patient is severely nonadherent. In various studies, that’s 7%-29% of SLE patients who are supposedly on hydroxychloroquine.

Also, investigators at Johns Hopkins University, Baltimore, have analyzed prospective data from the Hopkins Lupus Cohort and determined that at the first clinic visit after going on a maximum of 400 mg/day of hydroxychloroquine, only 44% of participants had a blood drug level above the 500-ng/mL threshold indicative of adherence.

Importantly, however, the Hopkins researchers also demonstrated that with repeated brief counseling of nonadherent patients as to why hydroxychloroquine is the most important medication they take for their SLE, adherence climbed in stepwise fashion with each visit in which the drug blood level was assessed: With no prior measurement, adherence was 56%; with one prior measurement, it jumped to 69%; with two, 77% of patients were adherent to hydroxychloroquine; and with three or more prior blood level checks, adherence rose to 80% (J Rheumatol. 2015 Nov;42[11]:2092-7).

It is well established that hydroxychloroquine prevents SLE flares, protects against thrombotic events, diabetes, dyslipidemia, and lupus-induced organ damage, and improves survival. Dr. Costedoat-Chalumeau’s final words on hydroxychloroquine adherence: ”Drugs don’t work in people who don’t take them.”

She reported having no financial conflicts regarding her presentation.