Optimizing Isotretinoin Dosing for Acne

Source: Lai J, Barbieri JS. Acne relapse and isotretinoin retrial in patients with acne. JAMA Dermatology. Published online ahead of print, January 15, 2025. doi: 10.1001/jamadermatol.2024.5416.Investigators from Harvard Medical School conducted a retrospective study to assess the rate of acne relapse among adolescents and adults treated with isotretinoin and to identify risk factors for relapse. They also assessed rates of isotretinoin retrial in these patients. For the study, data were abstracted from the MarketScan database, which includes commercial insurance claims data on 1.85 million patients in the US with an ICD-10 diagnostic code for acne between 2017 and 2020. Demographic, inpatient, and outpatient encounters and pharmacy claims information also are in the database. Study participants were patients ≥12 years old with a diagnosis of acne who were treated with isotretinoin for at least 4 months and had ≥1 year of follow-up after completion of a course of the medication. The primary outcomes were acne relapse, defined as ≥1 encounter with an ICD-10 code for acne and a prescription for a systemic acne medication, and isotretinoin retrial, defined as a new prescription following completion of the initial course of treatment. Cox hazard proportional hazards regression was used to identify predictors of these outcomes. Covariates in the model included age, female sex, having a dermatologist provider, duration of treatment, maximum daily dose of isotretinoin, and cumulative dose.Data on 19,907 patients with acne who were treated with isotretinoin were included in the analysis. The mean age of study participants was 20.6 ±7.8 years, 52.8% were female, and 87% were treated by a dermatologist provider. The mean initial course of isotretinoin treatment was 45.6 ±1.6 months, with a mean maximum daily dose of 0.93 ±0.27 mg/kg and mean cumulative dose of 132.4 ±47.2 mg/kg. Among the study participants, 4,482 (22.5%) had acne relapse occurring a median of 7.5 months after completing their initial isotretinoin treatment, and 1,639 (8.2%) had an isotretinoin retrial. In the multivariate analysis, female sex (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.35, 1.52) and having a dermatologist provider (HR, 1.21; 95% CI, 1.11, 1.33) were associated with significantly higher chance of acne relapse and higher cumulative dosage of isotretinoin with a lower risk (HR, 0.996; 95% CI, 0.995, 0.997). Younger age, female sex, and higher cumulative dosage of isotretinoin were associated with a significantly lower risk of isotretinoin retrial, and dermatologist provider with a significantly higher chance.The authors conclude that a higher cumulative dosage of isotretinoin, but not daily dose, was associated with a lower risk of acne relapse and isotretinoin relapse.Dr Raphael has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Acne can severely impact the health-related quality of life of adolescents, increasing the risk of depression, bullying, and suicidal ideation.1 Despite this, it often goes undertreated, even in youths with moderate to severe symptoms.2 The American Academy of Dermatology recommends the use of isotretinoin for individuals with severe acne, especially those with scarring or psychosocial burden, who fail standard or topical treatment.1The current study has several strengths and fills an important gap in the literature by providing reliable estimates of acne recurrence risk. This study is amongst the largest available single studies of isotretinoin outcomes.3 As the study was based on claims data and the inclusion criteria considered the duration of treatment and follow-up, it is unlikely that the recurrence rate was underestimated due to loss to follow-up or overestimated due to inappropriate initial treatment. By defining relapse as the need for systemic acne therapy, the current study’s findings represent recurrence rates of moderate or severe symptoms.The current researchers also explore the optimum daily and cumulative dose for isotretinoin. While previous investigators have suggested that low daily doses (<0.5 mg/kg/day) may be effective for mild to moderate acne, information on relapse rates is limited.4,5 In the current study, a higher daily dose did not protect against acne relapse if a cumulative dose of >120 mg/kg was reached. This finding suggests that a shared decision-making approach could be used to individualize treatment plans to meet cumulative-dose thresholds and clinical goals.A limitation of the current study is the lack of weight data for individual participants in the data set. The authors used the population mean weight for age and sex to calculate weight-based daily and cumulative dosing. While the large sample size mitigates against some accuracy loss, the lack of patient-specific metrics reduces the reliability of the study conclusions.The likelihood of relapse after isotretinoin courses is lower if conventional cumulative dose thresholds (ie, >120 mg/kg) are met.