Increased Cumulative Isotretinoin Doses Linked to Lower Acne Relapse Rates

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Greater cumulative doses of isotretinoin are linked to decreased rates of acne relapse occurrences and isotretinoin retrial, new findings suggest, although this is provided that dosing increases are not daily.¹

These results represent the conclusion of a recent study authored in part by Jenny Lai, PhD, from the department of dermatology at Brigham and Women’s Hospital in Boston. Lai et al. sought to identify the characteristics and factors which are associated with acne relapse following isotretinoin therapy for patients with this skin condition.

The investigators noted that prior observational research had yielded findings that varied widely when assessing the rates and predictive factors linked to acne relapse and associated with isotretinoin retrial.^2,3

“The purpose of this study was to assess the rates of acne relapse and isotretinoin retrial and identify factors associated with these outcomes in patients who completed a first course of isotretinoin,” Lai and colleagues wrote.¹

Design Details

The research team implemented data drawn from the MarketScan commercial claims database and conducted a retrospective cohort study that looked into the period from January 2017 - December 2020. The claims database the team utilized includes de-identified claims of over 1.85 million people who had at least a single claim connected to a diagnosis of acne.

Patients’ sex and age were covered in the database as well as longitudinal information on outpatient, inpatient, and pharmacy claims. Overall, the investigators assessed data on individuals aged 12 years or older who had been provided treatment with isotretinoin for 4 or more months and had been continuously enrolled in insurance for 1 year after the conclusion of their treatment course.

The investigative team determined that the index date would be the date marking the end of the first isotretinoin course. They evaluated outcomes among the study subjects over at least a single year of follow-up from this point.

The researchers defined relapse of acne as the receipt of a prescription for a systemic acne therapy accompanied by a clinical meeting for the skin condition taking place after the index date. They identified a retrial of isotretinoin by a subsequent prescription for isotretinoin after the aforementioned index date.

The investigators consolidated instances of isotretinoin prescriptions with gaps of up to 60 days between start dates into a single course to account for possible nonadherence or delays. Data analyses for the trial were carried out between June - August 2024, with the research team using multivariable Cox proportional hazards regression to determine any links between demographic and treatment characteristics and the likelihood of acne relapse or retrial of isotretinoin.

Notable Findings

The investigators completed the study with an evaluation of 19,907 individuals, 52.8% of whom were reported as female and all of whom had a mean age of 20.6 years. They found that 22.5% of the study subjects had an acne relapse and that 8.2% had been shown to experience an isotretinoin retrial.

One significant associated factor with a likelihood increase of acne relapse was being of the female sex (hazard ratio [HR], 1.43; 95% CI, 1.35-1.52). A factor associated with a diminished risk of acne relapse was a higher cumulative isotretinoin dosage (HR, 0.996; 95% CI, 0.995-0.997).

Despite this conclusion, the research team found that maximum daily isotretinoin doses did not diminish participants’ risk of relapse or retrial, and this was true regardless of whether subjects had been given conventional or high cumulative doses.

The team noted that female sex (HR, 0.68; 95% CI, 0.62-0.76) and higher cumulative isotretinoin doses (HR, 0.99; 95% CI, 0.98-0.99) were linked to diminished isotretinoin retrial rates. When they stratified the findings by cumulative dosage, the investigators found that higher cumulative dosages led to substantially lower rates of retrial in those given low (<120 mg/kg) and more conventional (120-220 mg/kg) cumulative doses.

However, they added that this effect had not been observed in participants showing higher cumulative doses (>220 mg/kg). The analysis also demonstrated a lack of protective association with a maximum daily dose (mg/kg/day) against acne relapse or retrial in those showing cumulative dosages of 120 mg/kg or more.

“This large cohort study identified factors associated with acne relapse and isotretinoin retrial that may guide treatment selection and prognosis,” they wrote. “Further research is needed to understand optimal strategies to prevent acne relapse among those at highest risk.”¹

References

1. ^{Lai J, Barbieri JS. Acne Relapse and Isotretinoin Retrial in Patients With Acne. JAMA Dermatol. Published online January 15, 2025. doi:10.1001/jamadermatol.2024.5416.}
2. ^{Skroza N, Tolino E, Balduzzi V, et al. Advantages of tailored isotretinoin treatment in moderate to severe acne: real-life data. Front Pharmacol. 2021;12:733526. doi:10.3389/fphar.2021.733526.}
3. ^{Morales-Cardona CA, Sánchez-Vanegas G. Acne relapse rate and predictors of relapse following treatment with oral isotretinoin. Actas Dermosifiliogr. 2013;104(1):61-66. doi:10.1016/j.ad.2012.05.004.}