Conference Coverage

Low-Dose Isotretinoin Tames Adult Acne

Major Finding: Sixteen weeks of low-dose isotretinoin at 5 mg/day in patients with persistent, low-grade adult acne resulted in a reduction in mean facial lesion count from 10.6 at baseline to 3.2, with a further 16 weeks of open-label isotretinoin dropping the lesion count to 1.3.

Data Source: This was a randomized, double-blind, placebo-controlled trial involving 58 adults aged 25-55 with persistent, low-grade acne since adolescence.

Disclosures: Dr. Rademaker’s investigator-initiated study was sponsored by Douglas Pharmaceuticals (an isotretinoin manufacturer in New Zealand). He had no other conflicts of interest.

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Long-Term Dosing a Realistic Option

In the United States, 5 mg of isotretinoin is not available, so dermatologists usually prescribe 10 mg per day as a low dose, according to Dr. Hilary E. Baldwin. She noted that she prescribes low-dose isotretinoin for adults, but not for getting patients from 70% to 100% clear.


Dr. Hilary E. Baldwin

"The FDA mandate for isotretinoin is that it be used for nodulocystic acne unresponsive to conventional therapy, and most of the patients in that 70%-100% group would not qualify, in my opinion. However, I certainly agree with the low dose, long-term approach, and it is often in my adult female patients who continue with their acne long into their mature years," she said in an interview.

She added that she often prescribes isotretinoin for women who tend to get one to two large acne lesions per week. "Topical products are ineffective on this type of lesion and it is hard to justify long-term use of antibiotics for 1-2 lesions per week. Antibiotic resistance is of crucial importance in these patients. Alternatives to long term/low dose isotretinoin include oral contraceptives and spironolactone. However, some adult patients exceed the safe-age contraindications for OCPs," she said.

Dr. Baldwin is vice chair of dermatology at the State University of New York, Brooklyn. She has received research funds from and/or serves as a consultant to Allergan, Coria, Galderma, GlaxoSmithKline, Graceway Pharmaceuticals, L’Oreal, Ortho Dermatologics, Medicis, and Sanofi-Aventis.


 

AT THE ANNUAL CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY

PRAGUE – Oral isotretinoin dosed at 5 mg per day proved to be highly effective, fast acting, and well tolerated for persistent, low-grade, adult acne in a randomized, double-blind clinical trial.

Results of this study provide physicians with evidence supporting the use of low-dose isotretinoin in the management of adult acne, Dr. Marius Rademaker said at the annual congress of the European Academy of Dermatology and Venereology.

Dr. Marius Rademaker

"There’s a high degree of dissatisfaction with treatment among adult acne sufferers because of their usual slow response to the traditional acne therapies, the poor clearance, and the very high relapse rate when you stop treatment. The standards of a woman of 35 with adult acne are quite different from those of a 15-year-old. I think people no longer want 70% improvement, they want 100% clearance," said Dr. Rademaker, a dermatologist at Waikato Hospital in Hamilton, New Zealand.

There have been few randomized, controlled studies focusing on treatment of adult acne, he reported, adding that he could find no studies involving systemic antibiotics for acne in adults. He found a few studies on topical retinoid trials, but they only included a minority of adults. And, he found no studies assessing the effectiveness of low dose isotretinoin for adults.

Therefore, he conducted a randomized trial of isotretinoin at 5 mg/day to determine if a lower dose would be as effective and would have fewer adverse events than the standard dose of 0.5-1.0 mg/kg per day. Avoiding relapse upon discontinuation of isotretinoin appears to be more a function of the duration of sebaceous gland suppression – longer is better – than of cumulative dose, he added.

He reported on 58 adults aged 25-55 with low-grade, indolent acne that had persisted since adolescence. Nearly 90% were women. Participants were randomized double-blind to 16 weeks of isotretinoin 5 mg/day or placebo, followed by an additional 16 weeks of open-label isotretinoin in both study arms. The primary end point was the change in the number of facial acne lesions between baseline and week 16.

The acne lesion count in the isotretinoin group was reduced by half within the first 4 weeks of the study, from a mean baseline of 10.6 lesions. By week 16, the group’s mean acne lesion count had dropped to 3.2. After a further 16 weeks of open-label therapy, it had fallen to 1.3.

In contrast, the mean acne lesion count in the control group didn’t change significantly over the first 16 weeks from a baseline of 9.7 lesions. After a subsequent 16 weeks of open-label isotretinoin, acne count dropped to 3.9.

A secondary outcome measure was change in Dermatology Life Quality Index (DLQI) scores. From a mean baseline score of 4.8, indicative of moderate skin disease–related disability, the score fell to 1.3 after 16 weeks of double-blind isotretinoin and to 1.2 after another 16 weeks of open-label therapy. The mean DLQI score of 4.9 was unchanged in the control group after 16 weeks of placebo, but dropped to 2.3 after 16 weeks of open-label isotretinoin.

In an interview, Dr. Neil S. Goldberg, a dermatologist in Bronxville, N.Y, questioned the blindness of any study involving isotretinoin. "No isotretinoin study can be blinded. The side effects of isotretinoin, even low dose, are just too obvious."

Dr. Neil S. Goldberg

The most common side effect in the study was dry lips, which nearly two-thirds of patients reported while on isotretinoin. Dry skin, musculoskeletal aches and pains, dry eyes, and fatigue were less frequently reported. One patient withdrew from the study because of anxiety and mood changes that may or may not have been treatment related, Dr. Rademaker said.

He added that in his experience, after a year of treatment at 5 mg/day, virtually all patients with persistent low-grade adult acne no longer have any acne. He is pursing the possibilities of conducting a long-term, follow-up study.

"Isotretinoin seems to me to be just as valuable a treatment in adults as in teenagers," said Dr. Steven R. Feldman, professor of dermatology at Wake Forest Baptist Medical Center in Winston-Salem, N.C. "My standard approach is to use it in the same way, though using it in lower doses for longer periods of time is reasonable and often effective with fewer side effects." Caution is warranted, however, when prescribing isotretinoin to women of childbearing potential because of the drug’s known teratogenicity.

Dr. Steven R. Feldman

In response to audience questions about restrictions placed upon isotretinoin prescribing in New Zealand, Dr. Rademaker replied that his country’s pregnancy prevention plan requires patient education but not mandatory pregnancy tests. "And our pregnancy rates [for females on isotretinoin] are lower than in Europe or the U.S.," he said.

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