A 150mg/kg cumulative dose of isotretinoin provides no benefits to patients with moderate to severe cystic acne compared with a 120mg/kg dose, an Australian trial has found.

UNSW Professor Dedee Murrell and colleagues randomised 91 adolescents and young adults to receive either a cumulative isotretinoin dose of 120 mg/kg or 150mg/kg, tracking changes in lesion count and acne severity and 12 month relapse rates. Among their findings:

• Both groups showed comparative improvement in lesion counts and disease severity between baseline and treatment completion, with no significant differences between the doses,
• After 12 months, relapse rates were similar at 26.7% in the 120mg/kg group and 32.3% in the 150mg/kg group,
• Scarring did not worsen throughout the treatment period, while adverse events were mild.

Writing in JEADV, the authors said none of the data favoured a higher treatment dose across anatomical sites or time points.

“Although some studies have reported numerically lower relapse rates with higher cumulative exposure, these differences are often small and rarely reach statistical significance, and they may be accompanied by a greater burden of adverse effects,” they said.

Professor Dedee Murrell.

By contrast, this study found a numerically higher, though not statistically significant, relapse rate among patients on the 150mg/kg dose.

“This finding was consistent when relapse was restricted to systemic retreatment only, supporting the robustness of the results,” the research team said.

“This observation reinforces the notion that exceeding the standard cumulative dose does not necessarily improve long-term outcomes.”

Multivariable analysis showed that dose, sex and baseline lesion numbers could not independently predict relapse risk at 12 months.

Cumulative dosing targets not a ‘rigid determinant’ of remission

The authors noted the current concept of a target cumulative isotretinoin dose of 120-150mg/kg is widely used to prevent patient relapse, but until this point there has been limited randomised trial data to compare outcomes between dosing strategies.

Increasing the dose towards the top end of the range did not deliver benefits to patients, they said.

“These findings suggest that cumulative dosing should be viewed as a pragmatic therapeutic framework rather than a rigid determinant of long-term remission.”

The findings supported a more individualised approach to dosing, the investigators concluded, though the 120mg/kg dose appeared sufficient for achieving sustained acne improvement.

“Our findings support 120mg/kg as an effective cumulative target for most patients with moderate-to-severe acne vulgaris.”