Retinopathy Risk in Lupus Increases With Longer Hydroxychloroquine Use

[lupus-support1]

Hydroxychloroquine retinopathy in lupus patients.

Katie Robinson

October 1, 2019

The incidence of retinopathy among systemic lupus erythematosus (SLE) patents treated with hydroxychloroquine increased with longer treatment duration, but could be predicted by monitoring blood levels of the drug, say researchers writing in Arthritis & Rheumatology this month.

Hydroxychloroquine is one of only four medications approved in the U.S. for patients with systemic lupus. It is the only medication that has been shown to improve survival for patients with systemic lupus, in part, by reducing flares by as much as 50 percent. However, the treatment is associated with the development of retinopathy over time.

In this study, which was led by Michelle Petri, M.D. M.P.H., of Johns Hopkins University School of Medicine in Baltimore, researchers assessed the risk of retinopathy by examining the clinical characteristics and hydroxychloroquine levels in the blood of 537 patients with systemic lupus (494 females, 46.9 percent Caucasian and 41.5 percent African American). They found an overall frequency of retinopathy as 4.3 percent with a 1 percent risk of developing retinopathy within the first five years of treatment. The risk dropped to 1.8 percent between years six and 10; 3.3 percent between years 11 to 15 years; 11.5 percent between years 16 to 20; and, 8 percent after 21 years.

Among patients in the lowest mean tertile of hydroxychloroquine blood levels (0 to 741 ng/mL), the rate of retinopathy was 1.2 percent, 3.7 percent for those with blood levels of 741.5 to 1,176.5 ng/mL and 7.9 percent for patients with levels of 1,177 to 3,513 ng/mL (P for trend = 0.0027).

Higher toxicity rates were seen in patients with a high body mass index, patients older than 60 years (10.1 percent versus 0.5% for those more than 45 years old) and with a longer duration of treatment. African Americans had lower daily doses of hydroxychloroquine than Caucasians (4.46 versus 4.84 mg), but there were no differences in blood levels or retinopathy rates between African Americans and Caucasians. The prevalence of retinal toxicity increased in accordance with the tertile blood levels, from 1.2 percent at the lowest to 6.7 percent at the highest tertile.

"We found the results on high body mass index particularly concerning, as we capped the dose of hydroxychloroquine at 400 mg daily, no matter how high the body mass index," the authors wrote.

This is the first study that focuses on assessing retinopathy risk by tracking hydroxychloroquine blood levels.

Despite the benefits of treatment, which may also include anti-thrombotic and anti-diabetic effects and complete renal remission when given in combination with mycophenolate mofetil, the risks have been well documented. In 2016, the American Academy of Ophthalmology changed the recommended dosing of hydroxychloroquine from 6.5 mg/kg to less than 5 mg/kg, following a large retrospective study that found retinopathy rates of almost 20 percent by year 20 of use.

"Our data agree that the prevalence of hydroxychloroquine retinopathy, using newer screening technologies, is much higher than previously reported," the authors wrote, “Monitoring hydroxychloroquine blood levels is an important step to improved medication adherence in patients with SLE. We now introduce the concept of hydroxychloroquine blood level monitoring to reduce overdosage. The clinical impact of our study is that practitioners would be able to either decrease hydroxychloroquine dose or increase monitoring in patients with the highest tertile of blood levels.”

REFERENCE

Michelle Petri, Marwa Elkhalifa, Jessica Li, et al. “Hydroxychloroquine Blood Levels Predict Hydroxychloroquine Retinopathy.” Arthritis and Rheumatology. September 18, 2019. doi: 10.1002/art.41121

Source: rheumatologynetwork.com/lup...

LUpus Patients Understanding & Support (LUPUS):

lupus-support.org/topic/312...

PLEASE DO NOT PANIC!

BEFORE TAKING HYDROXYCHLOROQUINE (PLAQUENIL), SEE AN OPHTHALMOLOGIST (A MEDICAL DOCTOR, NOT AN OPTICIAN) WHO WILL MONITOR YOU CLOSELY. ANY SIGN OF TOXICITY, THE DRUG WILL BE STOPPED BEFORE ANY DAMAGE. IT IS IMPORTANT TO SEE YOUR OPHTHALMOLOGIST REGULARLY WHO WILL ORDER APPROPRIATE TESTS.

–Shimon Peres, Tomorrow is Now, 1977.

–Shimon Peres, Tomorrow is Now, 1977.E–Shimon Peres, Tomorrow is Now, 1977.

PS I have been taking hydroxychloroquine for over 20 years, taking 400 mgs daily.

[Bellaflowe Volunteer]

This is a little concerning. I actually booked an appointment with my optometrist today and she told me that now people who take hydroxychloroquine should have more in-depth tests in hospital by an eye specialist. She said that, although, she could check my sight and ‘macular’ (I think that’s the word she used), specialist equipment in hospital is needed and should be organised by my rheumatologist. I didn’t know this until today, so it’s strange that you’ve just posted this!

Thanks for the info!

Suzy

[lupus-support1 Administrator in reply to Bellaflowe]

Provided you see an ophthalmologist & have regular tests, you should not be too anxious!

[fabwheelie Moderator Moderator]

Since this study was published, everyone has taken the findings on board, there's been ba change in guidelines to dose of hydroxychloroquine so drs are now trying to hit the 5mg per Kg dose guidelines.... this in reality is meaning thatsome patients are being asked to try reduced dosages (especially those who are 12 stones or less in weight). Drs actually should have always been aiming for "lowest dose that works for you" and one way they do that is sometimes ask you to take different doses on different days as they don't make a 100mg size hydroxychloroquine tablet but for example alternative days dosing such as alternative days taking 200mg one day and 400mg on the next, or taking 200mg on alternative days only, even things like take drug 5 days a week but not at weekend, all results in overall average lower dose over the week

There's also new guidelines for the eye test screening. I'll post a separate comment about that.

Please don't worry about this study the risk of retinopathy side effects from hydroxychloroquine is very rare, however because it is known as a risk it is monitored.

[fabwheelie Moderator Moderator]

The guidelines for eye test screening are changing as a result of a report by Royal college of opthalmology

Here is a link to some info as it's a good leaflet that explains about this issue, and the tests that are now recommended

It's new guidelines since the American study mentioned in this post, and it's likely that hospital opthalmology are now going to be very busy as I'd expect they have to be seeing all the new patients plus catch up with patients who've been on hydroxy a long time (I've been on it very long term and my rhemy consultant referred me as I've had the more specific tests, they do a few photos including one that makes your eyes blurry whilst they photo..... You can't drive after that test as it takes a few hours for effects of drops to fully wear off. I'd also advise take some sunglasses for use on journey home / first hour afterwards as the drops do make you very sensitive to bright lights

I do also personally always get annual checkup via Specsavers opticians who knows I'm on hydroxychloroquine and they do extra annual checks because of that including Amsler grid, vision fields tests and colour vision tests as they can help pick up if any changes to your eyes due to the hydroxychloroquine

macularsociety.org/resource...

[lupus-support1 Administrator]

These specialist eye tests can be very uncomfortable but ensure the toxicity has not affected the eyes. These tests will show up toxicity before any long term damage.

The problem, as you are probably aware, is the reduction in hydroxychloroquine, the staple medication for SLE.

I recently halved my dose & was OK for a month or two. By 10 weeks, I was going to rest almost every afternoon, which is intolerable.

My tests thus far has not shown toxicity but this doesn’t mean I don’t need to have these highly specialized tests. Macular degeneration is only one problem.

As always it’s a balance. All rheumatologists want us to take as few medications as possible vs quality of life.

It is ESSENTIAL to see an ophthalmologist every year and have these tests, even though they can be very unpleasant. Always take someone with you.