More accurate risk measurements
This news organization asked study coauthor April Jorge, MD, assistant professor of medicine in the division of rheumatology, allergy, and immunology at Massachusetts General Hospital and Harvard Medical School, Boston, to discuss the study, how it correlates to past research, and what it adds that’s new and useful to rheumatologists and ophthalmologists:
Question: Your research found that a higher dose of HCQ in the first 5 years of treatment led to a greater risk of retinopathy. Is there any indication that a lower dose given more frequently, either within that 5-year period or longer, would pose a similar risk?
Answer: In our study, we assessed the HCQ dose in the first 5 years of use but followed patients who continued the medication longer than 5 years, through up to 15 years of use. Therefore, we compared the risk of HCQ retinopathy associated with different HCQ dosages but for the same duration of use. We found that for any dose of HCQ, the risk of retinopathy increases the longer the medication is used. However, patients who used a higher dose of HCQ had a higher risk of developing retinopathy over time.
Dr. April Jorge
Although current guidelines recommend avoiding any HCQ dose over 5 mg/kg per day to reduce the risk of retinopathy, we found a higher risk of retinopathy associated with dosing over 6 mg/kg per day than between 5 and 6 mg/kg per day and the lowest risk with dosing under 5 mg/kg per day.
Q: How does your study align with and/or expand upon previous research regarding HCQ risk?
A: An important prior study of hydroxychloroquine retinopathy was the 2014 study by Ronald B. Melles, MD, and Michael F. Marmor, MD, published in JAMA Ophthalmology. Prior to our present study, that was the largest study to use the modern screening method (optical coherence tomography) to detect HCQ retinopathy. That screening tool is more sensitive than older methods, so it can detect early/mild cases of retinopathy that are typically asymptomatic. Compared to older studies, that 2014 study found a much higher risk of HCQ retinopathy than was previously appreciated.
However, that 2014 study did have some key limitations that could affect the risk estimates, such as using prevalent cases. A key feature of our present study is that we took several important steps to generate more accurate risk estimates. This included using an incident user cohort and detecting incident retinopathy cases through serial review of optical coherence tomography (screening) studies.
To achieve a high degree of methodologic rigor in correctly identifying retinopathy outcomes, we had expert ophthalmologists perform masked adjudication of all screening studies, and we assessed the intra-rater reliability of these study interpretations. Therefore, our study adds to the literature more accurate estimates of retinopathy risk. We found a lower cumulative incidence of retinopathy than was identified in the 2014 study, but the risk is still noteworthy.
Also unique to our study, we graded the severity of HCQ retinopathy outcomes. This was important, as we found that the majority of retinopathy cases detected through routine screening are mild and presumed to be asymptomatic. This will likely be reassuring news for patients that we can screen for this adverse event to detect it early and prevent vision loss.
Another important difference was that we assessed the risk of retinopathy associated with using over 6 mg/kg per day, between 5 and 6 mg/kg per day, and less than 5 mg/kg per day, whereas the highest dosing group assessed in the 2014 study included all patients using over 5 mg/kg per day. The risk was considerably higher in the > 6 mg/kg per day group than in the 5-6 mg/kg per day group.
Q: How can rheumatologists and ophthalmologists use this new information specifically to better treat their patients?
A: Our study provides more accurate estimates of the risk of HCQ retinopathy than in prior studies. These risk estimates can be used when rheumatologists (and other clinicians who prescribe HCQ) consider the risks and benefits of this otherwise important and well-tolerated medication. The risk associated with different dose ranges could also inform dosing decisions, since dosing over 6 mg/kg per day may be more of a concern than using doses in the 5-6 mg/kg range. Ophthalmologists can also use these new risk estimates to counsel patients of the importance of HCQ retinopathy screening and can also hopefully provide some reassurance to patients that the risk of severe retinopathy is low as long as they are being monitored.
The study authors were supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Rheumatology Research Foundation. The authors report no relevant financial relationships. Dr. Bose and Dr. Mirza had no relevant disclosures.
A version of this article first appeared on Medscape.com.