Study Examines Acne Relapse and Isotretinoin Retrial

Among patients treated with isotretinoin for acne, approximately one fifth experienced a relapse that required additional treatment with systemic medication, and 8.2% underwent a retrial with isotretinoin, in a cohort study that used national claims data.

In addition, low (under 0.5 mg/kg/d), conventional (0.5-1.0 mg/kg/d), and high (> 1 mg/kg/d) daily dose regimens were associated with similar rates of long-term clearance and isotretinoin retrial, provided that a sufficient cumulative dose was achieved.

Those are key findings from an analysis of national commercial claims data that aimed to assess acne relapse and isotretinoin retrial rates and to identify associated factors among patients with acne who received a course of isotretinoin.

“These findings reinforce the practice of prioritizing cumulative dose and treating to clinical endpoints over maximizing daily dose when using isotretinoin,” the study’s lead senior author, John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, told this news organization. “This allows for individualized treatment strategies that optimize long-term clearance while minimizing side effects,” he commented. “Additionally, the results emphasize the need to manage expectations as recurrence is relatively common. For this reason, I describe isotretinoin as causing a ‘remission’ rather than a ‘cure’ of acne.”

For the study, which was published on January 15, 2025, in JAMA Dermatology, Barbieri and Jenny Lai, PhD, a student at Harvard Medical School, used MarketScan commercial claims data from January 1, 2017, to December 31, 2020, to identify patients aged 12 years or older with acne who had received isotretinoin for 4 months or longer, and who had at least 1 year of continuous enrollment after completing isotretinoin treatment. They used multivariable Cox proportional hazards regression to assess the associations between patient demographics, treatment characteristics, and acne relapse, as well as the need for an isotretinoin retrial.

The study cohort included 19,907 patients with a mean age of 20.6 years. More than half of the patients (10,504 or 52.8%) were women, 4482 (22.5%) experienced acne relapse over a median of 7.5 months, and 1639 (8.2%) underwent an isotretinoin retrial. Multivariable Cox proportional hazards regression revealed that female sex was significantly associated with increased rates of acne relapse (hazard ratio [HR], 1.43; 95% CI, 1.35-1.52; P P 

In other findings, daily dose was not associated with decreased risk for acne relapse or isotretinoin retrial among those with conventional and high cumulative dosages. Female sex (HR, 0.68; 95% CI, 0.62-0.76) and isotretinoin cumulative dosage (HR, 0.990; 95% CI, 0.989-0.993) were associated with decreased rates of isotretinoin retrial. Stratification based on cumulative dosage revealed that higher cumulative dosages were linked to lower rates of retrial among patients with low ( 220 mg/kg) dosages. Additionally, the maximum daily dose did not show a negative association with acne relapse or isotretinoin retrial in patients who received a cumulative dosage of 120 mg/kg or more.

“Given that prior studies had generally supported that higher cumulative dose is associated with lower rates of recurrence, I was a little surprised that while we observed this effect for cumulative doses under 220 mg/kg, it did not appear that higher cumulative dose beyond 220 mg/kg was associated with reduced risk of recurrence,” Barbieri said. “This finding suggests that while higher cumulative dose can help reduce the likelihood of recurrence, there does appear to be a limit to this effect, and there may not be much benefit in going beyond 220 mg/kg.”

Regarding other clinical implications of the findings, Barbieri emphasized that maximizing long-term clearance with isotretinoin isn’t always the primary goal. “As some of the risks, such as chronic skin and eye dryness, might also be dependent on cumulative dose, we should be thoughtful about balancing the risks and benefits of higher cumulative dose regimens and tailor our approach to individual patient goals and preferences,” he said. “Even among those whose acne did recur, they often had milder acne that could be managed with topical medications alone.”

The MarketScan database lacked data on patient weight and clinical data on acne severity at the time of isotretinoin initiation and discontinuation, which the authors acknowledged as study limitations.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, DC, who was asked to comment on the study, said that the analysis “corroborated what is widely held: That higher cumulative dose over an entire isotretinoin course is associated with less relapse. Interestingly, while only 8% of patients required an additional course of isotretinoin after discontinuation more than two thirds of those who relapsed did so within the first year after discontinuation.”

Because many clinicians prescribe a topical retinoid or benzoyl peroxide to use for a while after isotretinoin therapy completion, he continued, “I wonder if the study could be expanded to analyze if the use of a topical for 6 months or more after therapy completion is associated with even less a need for a future isotretinoin course.”

No funding source for the study was noted. Barbieri reported consulting fees from Dexcel Pharma and Honeydew Care outside the submitted work. Green disclosed that he is a speaker, consultant, or investigator for Galderma and Ortho Dermatologics.