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Questions about optimal dosing of isotretinoin persist, expert says


 

FROM ODAC 2022

Acne fulminans

Dr. Thiboutot was part of a panel of experts who assembled guidelines on the classification, management, and prevention of acne fulminans, published in 2017. “Acne fulminans can be induced by isotretinoin or it can occur on its own. If you have someone who has a lot of inflammation, a lot of cysts and nodules, it’s probably best to start them on a lower dose with or without prednisone,” she said.

Age at treatment is another variable that can affect the duration of response to isotretinoin. “If the patient is very young when they need isotretinoin, it’s highly likely that they will need it again,” Dr. Thiboutot said. “Also, adult females often need a repeat dose of isotretinoin. The cumulative dose is important, and the presence of truncal acne is a factor affecting duration of response. Truncal acne takes longer to clear, and it oftentimes needs a longer treatment course.”

Data from the iPledge database indicate that 37% of 10- to 11-year-olds needed a repeat course of isotretinoin, “and as you get older, the need for retreatment is less,” she said.

High-dose versus low-dose isotretinoin

A slow, low-dose approach to the use of isotretinoin in practice can minimize side effects and cystic flares, according to Dr. Thiboutot. “The cons are that you could have a longer treatment duration, you might need more patient visits, and it creates more prolonged drug exposure in patients who can become pregnant,” she said.

“The pros of a high-dose strategy include a shorter treatment duration and potential costs savings. The cons are that there is an increased risk of side effects and a risk of cystic flare. It seems that the general agreement is to treat until clearance and then treat for another 2 months. A clear definition of acne relapse is needed as well as prospective studies to optimize dosing.”

Dr. Thiboutot disclosed that she is a consultant Galderma and Novartis. She has also performed clinical trials for Galderma, Cassiopea, and Foamix.

Commentary by Robert Sidbury, MD, MPH

Isotretinoin has been around for a long time – 40-plus years, to be exact. Despite this cumulative experience, ideal dosing and duration remain uncertain. Many providers have evolved from a “one size fits all” approach (for example, 1 mg/kg of body weight per day for 4-6 months) to a more tailored and nuanced strategy. Dr. Thiboutot validates the need to individualize therapy and helps identify patients at higher risk for relapse. Younger patients are at greater risk for repeat courses of isotretinoin – Dr. Thiboutot cites a study showing 37% of 10- to 11-year-olds required a second course of isotretinoin. This could simply be a proxy for severity, which also augurs a more protracted course. Adult women and those with truncal acne also trend toward longer courses. Knowing these risk factors will help practitioners counsel proper expectations, tailor treatment courses, and thread the always challenging isotretinoin needle: Should one dose “low and slow” and court a longer risk window, or higher and faster, sometimes leading to a dryer disaster?

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/10/22.

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