High-Dose Isotretinoin Cuts Acne Relapse Risk without Upping Side Effects
November 07, 2013
By Anne Harding
NEW YORK (Reuters Health) Nov 06 - Patients treated for acne vulgaris with high-dose isotretinoin have a smaller risk of relapse without any significant increase in the risk of serious side effects, researchers have found.
Patients who received a cumulative dose of 220 milligrams per kilogram (mg/kg) were at lower risk of relapse and were less likely to require a repeat course of isotretinoin than those given a lower dose, Dr. Dean S. Morrell of the University of North Carolina at Chapel Hill and his colleagues found.
Isotretinoin is the most effective treatment for severe acne, but the drug carries the risk of adverse events ranging from xerosis and dermatitis to rarer, systemic effects such as elevations in cholesterol, triglycerides, or transaminase levels, Dr. Morrell and his colleagues note in their report, online October 30 in JAMA Dermatology. There is no consensus, they add, on the best dosage for optimizing treatment response while reducing adverse events.
In his own practice, Dr. Morrell told Reuters Health, he had observed that patients receiving the traditional dose of 120 to 150 mg/kg were coming back and requiring additional courses of medication.
"When we're using a medication like isotretinoin that costs a lot of money, requires monthly visits so time away from work and school, and lab tests, I think that if we can maximize the outcomes during that time that would be everyone's goal," he said.
Dr. Morrell gradually increased isotretinoin dosing for the patients he treated, and found that they seemed to be doing better with fewer relapses. They performed a retrospective review that showed 220 mg/kg was the dose at which results were significantly improved, without additional adverse effects.
To prospectively examine the risks and benefits, Dr. Morrell and his team conducted a prospective observational study in which they compared patients who received a cumulative dose of 220 mg/kg or higher to those who received a lower cumulative dose. Patients had severe nodular-cystic acne that had not responded to other treatments, and received no other topical or prescription medications for their acne during the study.
There were 38 patients in the lower-dose group (mean cumulative dose 170.8 mg/kg) and 78 in the higher-dose group (mean cumulative dose 309.8 mg/kg).
Overall, a third of the patients had relapsed by 12 months, meaning they needed another prescription acne medication, and about 2% required another course of isotretinoin. The relapse rate was 47.4% for the lower-dose group, versus 26.9% for the higher dose group (p=0.03); after adjustment for age, gender, race, treating physician and treatment duration, the relapse rates were 43.8% and 26.6%, respectively (p=0.22).
Fourteen percent of patients in the study had elevated lab values during treatment, and there was no significant difference between the high- and low-dose groups. Nearly all of the patients developed cheilitis and xerosis during treatment. Retinoid dermatitis occurred in 53.8% of patients in the high-dose group versus 31.6% of the low-dose group (p=0.02). The low- and high-dose groups reported similar rates of systemic effects, which included arthralgias, myalgias, and epistaxis.
In his practice, Dr. Morrell explained, he starts patients at 40 mg/day for the first month, then increases their dose to above 1 mg/kg daily, and slowly progresses toward 2 mg/kg daily. The goal is to reach a cumulative dose above 200 mg/kg, and for the patient to be acne-free for the last month that they are on the medication. This course of treatment takes six or seven months, according to Dr. Morrell, rather than the traditional five months.
Based on the results of the current study, Dr. Morrell said that this dosing regimen should be given to all patients on isotretinoin. "We get better outcomes, side effects are not significantly different, and the patients have less acne relapses and require less repeat courses of an expensive medication."
"This study suggests that a 'high-and-dry' approach to isotretinoin dosing may lead to better long-term outcomes without increased risk for significant adverse effects," Dr. Thomas J. McIntee of Marshfield Clinic in Marshfield, Wisconsin, and Dr. Anna Bruckner of the University of Colorado in Aurora write in a commentary accompanying the study. "Comparison with prior studies is difficult, however, because of wide variation in methods of acne assessment and in the definition of outcomes, such as relapse and retrial."
They conclude: "Standardization of acne severity assessment and therapeutic outcomes is needed to compare studies effectively."
JAMA Dermatology 2013.