Isotretinoin for acne: Higher total dose exposure, lower relapse risk?

A large cohort study suggests that for patients with acne who received an isotretinoin treatment course, the cumulative dosage taken, rather than the daily dose, is a key factor for reducing the risk of relapse and treatment retrial.

Analysis of data from the MarketScan commercial claims database showed that acne relapse rates were higher among female than male patients (hazard ratio [HR], 1.43, 95 percent confidence interval [CI], 1.35-1.52). However, a risk decrease was seen with isotretinoin cumulative dosage (mg/kg) (HR, 0.996, 95 percent CI, 0.995–0.997). [JAMA Dermatol 2025;doi:10.1001/jamadermatol.2024.5416]

In terms of isotretinoin retrial, both female sex (HR, 0.68, 95 percent CI, 0.62–0.76) and isotretinoin cumulative dosage (HR, 0.99, 95 percent CI, 0.98–0.99) were associated with a decreased rate.

Meanwhile, daily dose did not impact the rates of acne relapse or isotretinoin retrial among patients who received either conventional (120–220 mg/kg) or high (>220 mg/kg) cumulative dosages.

In an analysis stratified by cumulative isotretinoin dosage, higher cumulative dosage had a protective effect on the rates of relapse and retrial among patients who received low cumulative isotretinoin dosage (<120 mg/kg; HR, 0.80, 95 percent CI, 0.65–0.99 and HR, 0.98, 95 percent CI, 0.98–0.99, respectively).

“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 adverse effects from higher daily dose leading to earlier course termination, prescriber preferences, or confounding related to disease severity,” the investigators said. [JEADV Clin Pract 2023;2:432-449]

“Moreover, even without considering cumulative dosage, the rate of acne relapse was comparable between conventional (0.5–1.0 mg/kg/d) and high (>1.0 mg/kg/d) daily doses (22.6 percent vs 21.7 percent),” they added.

Taken together, the findings point to the potential for a personalized approach to isotretinoin dosing, according to the investigators. Daily dosing can be adjusted based on individual patient needs, enabling clinicians to balance treatment efficacy with potential side effects and patient preferences for treatment duration, they added.

The investigators further highlighted that doses exceeding 220 mg/kg may not provide additional benefit with regard to preventing acne relapse or the need for another course of isotretinoin.

The study included 19,907 patients (mean age 20.6 years, 52.8 percent female) with acne who were at least 12 years of age and had received isotretinoin for 4 months or longer, with at least 1 year of continuous follow-up data after completion of isotretinoin. Of these, 4,482 (22.5 percent) had acne relapse and 1,639 (8.2 percent) underwent isotretinoin retrial.

The initial isotretinoin courses lasted a mean of 5.6 months, with a maximum daily dose of 0.93 mg/kg/d and cumulative dosage of 132.4 mg/kg. The mean follow-up time was 24.9 months.