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Study showed lower doses less effective.
Higher doses of isotretinoin can effectively treat patients with acne vulgaris and reduce the relapse rate without significantly increasing adverse events, according to a recent report published in JAMA Dermatology.
Rachel C. Blasiak, MD, MPH, and her colleagues from the department of dermatology, School of Medicine, University of North Carolina at Chapel Hill, reviewed the medical records of patients at their institution and discovered that lower doses of the drug was associated with higher relapse and retrial rates. The researchers then conducted a prospective observational study of 180 patients with severe nodular-cystic acne, to determine the effectiveness and safety of higher cumulative doses of isotretinoin (220 mg/kg or more).
Of the 180 patients, 116 (64%) completed the study and follow-up survey 12 months after the treatment. Approximately 52% were women, the mean age was 19.3 years, and the majority was white (74%). The mean cumulative dose of isotretinoin was 264.3 mg/kg with a mean treatment period of 6.3 months. In the lower-dose group, the mean cumulative dose was 170.8 mg/kg, and in the higher- dose group, the mean cumulative dose was 309.8 mg/kg. Treatments started August 1, 2008 and continued through August 31, 2009.
At the 12-month follow-up, patients in the high-dose group had a lower relapse rate (26.6%) compared with patients in the low-dose group (43.8%), after adjustment for age, sex, race, treating physician, and treatment duration. Most patients (97%) reported in the survey that their condition had improved with the isotretinoin treatment, and more than 55% did not need any further treatments with acne medication. Approximately 25% were treated with topical prescriptions at the 12-month follow-up, almost 15% used an over-the-counter medication, 1.7% were receiving an oral antibiotic, and 0.9% were being retreated with isotretinoin.
“Of the patients in the lower-dose group, 42.3% were given a prescription for another acne medication after completing isotretinoin compared with 28.1% in the high-dose group,” Blasiak wrote. “In the lower-dose group, 12.8% of patients reported using over-the-counter acne treatment compared with 16.2% of patient in the high-dose group. This difference was not statistically significant (P=.23).”
In the study, 14% of patients had laboratory abnormalities, with most occurring in the higher-dose group. Elevated liver enzyme levels were seen in the higher-dose group, with 6.4% having elevated aspartate aminotransferase (AST) levels and 1.3% having elevated alanine aminotransferase (ALT) levels. In this higher-dose group, 1.3% also had elevated cholesterol levels and 11.5% had elevated triglycerides. In the lower-dose group, 5.3% had elevated triglycerides.
Other adverse effects during treatment included cheilitis and xerosis, which was reported by most of the patients in both treatment groups. Patients in the higher-dose group also reported retinoid dermatitis at higher rates (53.8%) than the patients in the lower-dose group (31.6%). Systemic effects included arthralgias, myalgias, and epistaxis.
After the 12-month follow-up, patients continued to report cheilitis, xerosis, and headaches, with both groups experiencing similar rates. “At the 12-month follow-up, the percentage of patients reporting rash decreased to less than 10%, with no statistically significant difference between the dosing groups, suggesting that isotretinoin has a transient, dose-dependent effect,” Blasiak wrote.
“At 1 year after completion of isotretinoin therapy, we found that patients in the high-dose group had a significantly decreased risk of relapse, which was defined as the need for prescription acne medication. Our overall rate of retrial or retreatment with a second course of isotretinoin was so low that we are unable to draw conclusions about the effect of dose on retrial rate,” she concluded.