Cumulative isotretinoin dose affects acne recurrence rates

Key takeaways:

• Higher cumulative doses of isotretinoin showed a decreased risk for acne relapse.
• These findings suggest an individualized approach to care should be implemented.

The risk for acne relapse following isotretinoin use is reduced with higher cumulative doses, suggesting individualized treatment plans based on patients’ goals could maximize efficacy, according to researchers.

“A lot of times people think of isotretinoin as a permanent cure for acne. However, while 80% of people will not have any meaningful acne afterward, one out of five people go on to require treatment with another systemic medicine,” John Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the advanced acne therapeutics clinic at Brigham and Women’s Hospital, told Healio.

Using data from the MarketScan commercial claims database, Barbieri and Jenny Lai, PhD, of Harvard Medical School and Brigham and Women’s Hospital, evaluated claims from 19,907 patients who had used isotretinoin for at least 4 months to determine if they had a relapse in acne in the year after treatment.

John Barbieri

Relapses were identified by prescriptions for systemic acne treatments, including oral tetracycline antibiotics of at least 28 days, spironolactone and isotretinoin, or rates of topical acne prescriptions, including retinoids, antibiotics, benzoyl peroxide and combination treatments.

Of the 19,907 patients included in the analysis, 4,482 (22.5%) had acne relapse, with a rate of acne relapse being 12.9 per 100 person-years.

Using multivariate cox proportional hazards regression, the researchers determined that female patients were more likely to experience relapse compared with male patients, with a hazard ratio of 1.43 (95% CI, 1.35-1.52).

Investigators also evaluated isotretinoin cumulative dosage, maximum daily dose and treatment duration as factors in acne relapse.

Cumulative dosage was measured as low (< 120 mg/kg), conventional (120 mg/kg to 220 mg/kg) or high (> 220 mg/kg). Daily dosages were also measured and stratified as low (< 0.5 mg/kg per day), conventional (0.5 mg/kg to 1 mg/kg per day) or high (> 1 mg/kg per day).

There was a significant association between cumulative dosage and a lower rate of acne relapse among patients in the low cumulative dosage group, as well as a lower rate of isotretinoin retrial in the low and conventional groups. However, neither association was found among patients in the high cumulative dosage group, the researchers reported.

“This suggests that beyond 220 mg/kg, higher cumulative dosage may not be helpful for preventing acne relapse or the need for another course of isotretinoin,” they added.

Daily doses did not show an association with acne relapse rates.

“The low, conventional and high daily dosing regimens have similar rates of long-term clearance as long as they get to the same amount of cumulative dose,” Barbieri said.

Isotretinoin treatment is associated with a host of adverse events, which can be exacerbated by larger doses in some patients.

According to Barbieri, the results of this study and the knowledge of possible adverse events necessitates an individualized approach to care. For patients who prioritize acne clearance without relapse, using higher cumulative doses could be the correct choice, whereas patients who are prone to experiencing adverse events and would like to minimize those risks should be treated with lower doses.

“It’s listening to those different preferences and adjusting the treatment plan accordingly, not just having a one-size-fits-all approach and being thoughtful about selecting both the daily dose and cumulative dose to align with the patient’s goals,” he said.

For more information:

John Barbieri, MD, MBA, can be reached at jbarbieri@bwh.harvard.edu.