Hydroxychloroquine dosage recommendations often ignored


Evidence continues to mount that some North American rheumatologists are not following practice recommendations for minimizing the retinal toxicity risk of patients on long-term hydroxychloroquine treatment.

An audit of 100 patients seen at any of nine Canadian rheumatology clinics during early 2016 showed that 30% of patients were not on appropriate weight-based hydroxychloroquine dosages, and 13% of patients on the drug had not received a baseline retinal assessment during their first year of treatment, Sahil Koppikar, MD, reported in a poster presented at the annual meeting of the Canadian Rheumatology Association in Ottawa in February.

Dr. Sahil Koppikar of Queen's University, Kingston, Ontario. Courtesy Dr. Sahil Koppikar

Dr. Sahil Koppikar

“We are significantly below the standard of care for appropriately dosing and screening” patients treated with hydroxychloroquine (Plaquenil), concluded Dr. Koppikar, an internal medicine physician at Queens University in Kingston, Ont.

In a second recently reported study, researchers from the Chicago area documented that roughly half of the 554 rheumatology patients on hydroxychloroquine (HCQ) in a regional health system and seen by an ophthalmologist during 2009-2016 received an excessive dosage of the drug (Ophthalmology. 2017 Jan 30. doi: 10.1016/j.ophtha.2016.12.021).

Although his study did not examine reasons for the compliance shortfall, Dr. Koppikar proposed some possible factors.

HCQ comes only as 200-mg tablets, and prescribing intermediate dosages can be a challenge (although veteran clinicians know that a safe and easy way to dial down a dosage is to have the patient periodically skip a dose). Also, “it is more convenient to prescribe 400 mg daily rather than calculate an exact dosage,” Dr. Koppikar said in an interview. In addition, rheumatologists may be unaware that the prevalence of retinopathy in patients on HCQ is fairly common (about 8% in one large recent study), assessment for risk factors that heighten sensitivity to the drug isn’t always done, and appointments for retinal screening can fall through the cracks.

Dr. James T. Rosenbaum

Dr. James T. Rosenbaum

Compliance with today’s relatively new era of intensified retinal screening and capped dosages remains spotty, agreed James T. Rosenbaum, MD, professor and chief of arthritis and rheumatic diseases at Oregon Health & Science University in Portland. “Many rheumatologists used Plaquenil for decades, and it seemed safe and well tolerated,” but then ophthalmologists introduced optical coherence tomography [OCT] to assess retinal damage. OCT “changed our appreciation of the frequency of HCQ damage,” Dr. Rosenbaum said in an interview.

“It behooves rheumatologists to adopt the [HCQ] recommendations of the American Academy of Ophthalmology [AAO] because there is more toxicity than we previously appreciated,” he added. A new version of the AAO’s recommendations came out in March 2016.

The Committee on Rheumatologic Care of the American College of Rheumatology (ACR) has regularly updated the ACR’s position statement on screening for HCQ retinopathy and appropriate dosages, with the most recent version out in August 2016. The August statement “is very similar” to the AAO’s 2016 recommendations, said Vinicius Domingues, MD, a member of the committee and an ACR spokesman for the revision. The ACR statement acknowledges and cites the AAO 2016 recommendations.

Dr. Vinicius Domingues

Dr. Vinicius Domingues

“The main difference is that we [the ACR] do not necessarily advocate for regular OCT of the retina, as this technique is highly sensitive and can detect clinically irrelevant changes,” said Dr. Domingues, a rheumatologist at New York University Medical Center.

The ACR’s 2016 statement also does not fully endorse the AAO’s 2016 firm statement that “all patients using HCQ keep daily dosage less than 5.0 mg/kg real weight,” aside from “rare instances” when a higher dosage is needed to treat a “life-threatening disease.”

The ACR 2016 statement goes on to note that other authors have recommended a dosage of 6.5 mg/kg of actual body weight but capped at 400 mg/day and adjusted for renal insufficiency, and the ACR statement stops short of specifying which dosage strategy it recommends.

“The AAO recommendations are much more definitive and state more specifically what screening is recommended and what is a safe dosage,” commented Dr. Rosenbaum.

Dr. Domingues agreed that rheumatologist compliance with HCQ best practices has been spotty.

“In the past few years, more studies have used new ways to detect macular abnormalities and have identified a higher-than-expected incidence of maculopathy. Through lectures, CME, and articles, rheumatologists have received a tremendous amount of information with regard to screening and preventing retinal toxicity,” he said in an interview. “There are still gaps, and some rheumatologists still prescribe HCQ without taking into consideration the patient’s weight.”

That was a key finding in the poster presented at the Canadian Rheumatology Association by Dr. Koppikar and his collaborator on the study, Henry Averns, MD. The 100 patients assessed through the nine-clinic audit process averaged 58 years old, 81% were women, and patients had been taking HCQ for an average of just over 6 years, primarily for rheumatoid arthritis or systemic lupus erythematosus. Nearly two-thirds had a high risk for retinal toxicity. Based on the 2011 recommendations from the AAO and ACR, 17% of the patients were receiving an HCQ overdose that was more than 10% above the recommended dosage, and another 13% received a smaller overdose. If the 2016 dosage guidelines were applied, the extent of overdosing might be even greater, Dr. Koppikar said.

Dr. Koppikar and Dr. Averns said they believe that one way to address HCQ overdosing is by giving clinicians a dosing chart to easily find the right dosage for a patient’s weight. They have distributed these charts to the practices they audited and plan to do a follow-up audit to measure the effect of the intervention on HCQ prescribing.

Results from the initial clinical audit showed that “clinicians were not meeting standards, and we needed an intervention [a dosing chart] to implement a change,” Dr. Koppikar said. “Clinical audits are easy to implement, cost effective, and help improve patient care.”

Dr. Koppikar, Dr. Rosenbaum, Dr. Domingues, and Dr. Averns had no relevant financial disclosures.

On Twitter @mitchelzoler

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