By Abby S. Van Voorhees, MD, June 2, 2014
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Dean Morrell, MD, about his recent JAMA Dermatology article, “High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris.”
Dr. Van Voorhees: Isotretinoin has been used for the treatment of acne for many years. What made you decide to look at the use of high-dose isotretinoin?
Dr. Morrell: Due to its profound positive effect on patients, isotretinoin is one of my favorite medications. As I gained more clinical experience with isotretinoin, I noticed that some people required longer courses to reach total acne clearance. I also noticed that those who had overall higher cumulative doses tended to have better long-term outcomes and be less likely to require a second course of medication. Although not officially tracked, it was my impression that the adverse events with higher dosing seemed similar to patients with traditional lower dosing. With the outstanding assistance of Dr. Jackie Coloe Dosal, we performed a retrospective review of my patients’ outcomes, including reported adverse effects relative to their total cumulative dose. Statistically, we found that patients receiving cumulative dose greater than 219mg/kg were less likely to require an additional course of isotretinoin. In addition, adverse effects were not different in lower versus higher doses.
Since there are obvious issues with retrospective studies, several UNC Dermatology faculty members and resident physicians joined me to perform a prospective study to look at outcomes and potential adverse events. We gathered the information prospectively in a systematic format after which UNC medical students Rachel Blasiak and Christopher Stamey crunched the numbers to yield the results.
Dr. Van Voorhees: How was this higher dose of isotretinoin administered? In a larger daily dose? In a more prolonged course of treatment? How did you determine which patients were in the lower dose course versus those in the higher dose course? What criteria were used to determine when a single course of isotretinoin was completed?
Dr. Morrell: In the years prior to our study, my faculty colleagues Drs. Aida Lugo-Somolinos and Craig Burkhart were traditional isotretinoin dose prescribers. For the study, we decided to treat our patients in our own clinical patterns: Aida and Craig as traditional dose prescribers and me as the high dose prescriber. Otherwise, the laboratory monitoring and documentation of potential adverse events were identical.
My higher dose approach starts the same as traditional dosing as I start all patients at 40mg per day. During the second month, patients’ doses are increased to slightly greater than 1mg/kg/day (a 70kg patient would take 80mg each day; a 150kg patient would be increased to 160mg per day). Through the course of a high dose patient, I push the daily dose toward 2mg/kg/day (a 70kg patient would receive 120-140mg/day for the last two to three months of therapy). As a patient enters into months four to six of therapy, I calculate the total cumulative dose at monthly visits and watch for clearance of acne lesions. In the study, the definition of a completed course was similar: patients had completed a course of isotretinoin when they had achieved the targeted total dose (120mg/kg or 220mg/kg) AND were clear of all acne lesions for one month. The average total dose for our high dose group was 310mg/kg. Because we defined clearance of acne for one month on the medication plus the target dose as completion of a course of medication, our low dose group drifted a little higher (171mg/kg total dose) than traditional dosing (120mg/kg).