麻豆传媒

Factors such as higher cumulative doses of isotretinoin (Accutane) and female sex were associated with rates of acne relapse and isotretinoin retrial, according to a cohort study of commercial claims data.

Among nearly 20,000 patients taking isotretinoin, 22.5% of whom had acne relapse and 8.2% of whom had isotretinoin retrial, isotretinoin cumulative dosage was associated with a decreased rate of acne relapse (HR 0.996, 95% CI 0.995-0.997) and isotretinoin retrial (HR 0.99, 95% CI 0.98-0.99), reported Jenny Lai, PhD, and John S. Barbieri, MD, MBA, of Harvard Medical School and Brigham and Women's Hospital in Boston, and colleagues.

Meanwhile, female sex was significantly associated with increased rates of acne relapse (HR 1.43, 95% CI 1.35-1.52), and decreased rates of isotretinoin retrial (HR 0.68, 95% CI 0.62-0.76), they wrote in .

Of note, daily dose of isotretinoin was not associated with decreased risk of acne relapse or isotretinoin retrial among those with conventional and high cumulative dosages.

"When stratified by cumulative dosage, higher maximum daily dose was only associated with reduced rates of acne relapse and isotretinoin retrial for the low cumulative dosage group," Lai and Barbieri explained. "Within the conventional cumulative dosage group, higher maximum daily dose was associated with increased rates of acne relapse and isotretinoin retrial."

"The underlying factors for this association are uncertain, and could include increased from higher daily dose leading to earlier course termination, prescriber preferences, or confounding related to disease severity," they added.

Steve Daveluy, MD, of Wayne State University in Detroit, told 麻豆传媒 that "since the risk of side effects that can lead to intolerance increases with the daily dose, this study helped confirm my current practice of focusing on the cumulative dose and adjusting the daily dose based on tolerance."

"I typically prescribe around 1 mg/kg/day or a little higher, if I round up based on patient weight," he explained. "If a patient has intolerable side effects, we'll reduce the daily dose and extend the length of the treatment course to reach the same cumulative dose."

That "the benefit of higher cumulative dose was lost in the high-dose (>220 mg/kg) group suggests that it may not be beneficial to aim for any higher total dose," he suggested. "The absence of actual weight data means we don't truly know the weight-based daily or cumulative dose for each patient."

Daveluy also noted that "the increased risk of relapse in females both under and over age 18 makes sense, considering acne is more likely to manifest in adult females compared to men, usually due to the impact of hormone fluctuations. Whenever coverage and reimbursement will allow, I try to continue treatment for 1-2 months after the acne has cleared."

"The authors found that females were less likely to undergo repeat treatment with isotretinoin compared to males, and highlighted that this is likely due to our increased utilization of spironolactone," he added. "In my practice, I will prescribe a second course of isotretinoin in females who experience acne relapse, particularly for severe, widespread acne. If a female patient presents with acne in the typical hormonal pattern, with lesions concentrated along the jawline with premenstrual flares, then I'm more likely to start spironolactone than repeat isotretinoin."

This cohort study used data from the MarketScan commercial claims database from January 2017 through December 2020 to identify patients with acne ages 12 years and older who had received isotretinoin for 4 months or longer, with at least 1 year of continuous enrollment after completion of isotretinoin.

They included 19,907 patients in their study. Mean age was 20.6, and 52.8% were female. On average, maximum daily dose was 0.93 mg/kg, and cumulative dosage was 132.4 mg/kg.

The median time to acne relapse was 7.5 months. Of those who experienced relapse, 2.1% had a systemic acne prescription within 1 month of the index date, 25.8% within 1 to 3 months, 15.6% within 3 to 6 months, 25.2% within 6 to 12 months, and 31.3% after more than 12 months.

"Stratification by timing of isotretinoin retrial revealed that patients with isotretinoin retrial within 6 months had significantly lower retrial cumulative dosage and course duration than those with retrial after 6 months," Lai and Barbieri wrote. "These findings further suggest that early retrial courses may represent a continuation of the initial course due to a break in therapy due to substantial logistical barriers, or those with early retrial may reach acne clearance faster, potentially due to differences in acne severity at the time of retrial, or residual benefits from the initial course."

They acknowledged limitations to their study, including their use of average weight data from 2015 to 2018 for their study period of 2017 to 2020, and that acne relapse was defined by prescription of a systemic acne medication, which they noted could have been for reasons unrelated to acne relapse.

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