Conference Coverage

Fear of blindness hobbles hydroxychloroquine treatment of SLE



– The dosage of hydroxychloroquine (HCQ) for treating patients with systemic lupus erythematosus (SLE) is often overly influenced by fear that the drug could cause blindness, Michelle A. Petri, MD, said at the annual meeting of the American College of Rheumatology.

Dr. James T. Rosenbaum and Dr. Michelle A. Petri Mitchel L. Zoler/MDedge News

Dr. James T. Rosenbaum and Dr. Michelle A. Petri

HCQ “is the most important drug we have to treat lupus. It’s the only treatment shown to improve survival of lupus patients. There is no reason to make patients afraid of this very important drug. I am very concerned that fear of blindness is causing our patients to be less adherent” or making them receive an inadequate dosage, said Dr. Petri, a professor of medicine and the director of the Lupus Center at Johns Hopkins University in Baltimore. “I have had no patients who went blind on HCQ. A few patients developed retinopathy, but none went blind.”

Dr. Petri spoke about experiences with some of her SLE patients who were frightened by what an ophthalmologist told them about the retinal effects of HCQ and had their dosage of the drug unilaterally cut by the ophthalmologist.

“The message we should give patients is that retinopathy is a real complication that can happen, but usually not until after 16 years of treatment with HCQ, and we will work together to make sure you are regularly screened so that, if retinopathy developed, we would pick it up early and you’ll remain asymptomatic,” she said. ”We need to put the risk into perspective for our patients.”

Reports differ on the incidence of retinopathy in SLE patients on long-term HCQ treatment. During the session in which Dr. Petri spoke, James T. Rosenbaum, MD, cited a seminal report from 2014 that tracked 2,361 U.S. patients treated with HCQ daily for at least 5 years with regular retinal follow-up. The results showed a steady, cumulative increase in patients who developed retinopathy, an increase that was also dose dependent. For example, patients who received daily dosage of 5-5.9 mg/kg and took the drug for 20 or more years had a cumulative retinopathy incidence of 30% (JAMA Opthalmol. 2014 Dec;132[12]:1453-60). For patients on higher dosages, the cumulative risk at 20 years or longer jumped above 50%.

The findings from this study led directly to the most recent recommendations from the American Academy of Ophthalmology for retinopathy screening for patients on chronic HCQ treatment, said Dr. Rosenbaum, a professor of medicine and opthalmology at Oregon Health & Science University in Portland. The recommendations called for a dosage cap of less than 5 mg/kg real weight, a baseline retinal examination, and then at least annual follow-up examinations starting after 5 years of daily HCQ use, ideally using both automated visual fields and spectral-domain optical coherence tomography (Ophthalmology. 2016 June;123[6]:1386-94). The recommendations also noted that the presence of retinopathy risk factors, including renal disease or concomitant tamoxifen use, warrant starting screening at 5 years or sooner on HCQ.

Clinicians have often exceeded recommended dosage guidelines. Dr. Rosenbaum cited a 2017 report from one U.S. health care system that reviewed the treatment of 554 patients on HCQ and found that roughly half were overdosed in their starting regimen based on prevailing treatment recommendations (Opthalmology. 2017 May;124[5]:604-8).

But Dr. Petri contended that concerns about excessive HCQ dosages are overblown. At the meeting, she reported data showing a different perspective on the retinopathy risk of patients on chronic HCQ treatment. In a prospective series of 477 SLE patients on chronic HCQ treatment and followed at Johns Hopkins, the incidence of retinopathy was 10% among patients on treatment for 16 or more years, she reported in a talk at the meeting (Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2897).

A 10% retinopathy rate after 16 or more years on treatment “sounds a lot safer to patients” than rates as high as 30% or 50% that were reported in the JAMA Opthalmology report from 2014, Dr. Petri said. “There is a danger relying on one retrospective study,” she warned. In addition, the 10% risk for retinopathy is “manageable” when patients receive regular screening that produces early detection of retinal damage.

“There has been acceptance of suboptimal dosing of HCQ when discussion has only been about safety, not about efficacy. We need to put the risks into perspective and stop scaring patients.”

Dr. Petri presented her recommendations for treating SLE patients with HCQ: Treat with dosages as high as 6.5 mg/kg but without exceeding 400 mg/day, and cut the dosage for patients with renal insufficiency or failure, those with liver disease, or the elderly. In addition, Dr. Petri endorsed monitoring blood levels of HCQ. Data she reported at the meeting showed a roughly fourfold higher rate of retinopathy among patients who had a maximum HCQ blood level of 1,733 ng/mL or higher when compared with patients whose maximum level remained at 1,194 ng/mL or lower. Clinicians could use blood levels of HCQ to better focus screening and its intensity, she said. “We should embrace monitoring HCQ blood levels.”

Dr. Petri has been a consultant to Amgen, Exagen, GlaxoSmithKline, Inova Diagnostics, Janssen, Lilly, Merck, Novartis, Quintiles, and EMD Serono, and she has received research funding from AstraZeneca and Exagen. Dr. Rosenbaum has been a consultant to AbbVie, Eyevensys, Gilead, Janssen, Novartis, Regeneron, and Roche, and has received research funding from Pfizer.

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