Low Dose, High Rates of Success
Ultra-low dose isotretinoin is all many acne patients need
San Francisco - Low and ultra-low doses of isotretinoin are an effective therapy for many acne patients. This safer and cheaper solution can even be used continuously.
Gerd Plewig, M.D., believes that the doses of isotretinoin typically used in the United States and Europe are far too high. For many patients, as little as 2.5 mg twice a week, which he describes as "a drop of rain on a dusty road" is adequate.
Dermatologists all over the world already are treating some patients continuously with low doses of isotretinoin, according to Dr. Plewig, director, dermatology and allergy clinic, Ludwig-Maximilian University in Munich.
"When you talk to doctors in this country and other countries of the world, they use 10 mg twice a week or three times a week, which is a low or ultra-low dose. But nobody ever bothered to show and demonstrate that it works," he said. Thus, he and his team performed two clinical trials to assess its efficacy.
Study Spotlights Low Dosing In the first trial, 28 patients with acne conglobata and inflammatory acne took a low dose of isotretinoin: 20 mg/kg, 10 mg/kg, or 0.5 mg/kg body weight daily for six months. In the second study, 11 acne patients took an ultra low dose of isotretinoin: 2.5 mg to 5 mg daily or 2.5 mg twice a week for six months. Both trials involved multiple endpoints, including clinical grading, lesion counts, counts of follicular filaments (believed to be precursors to lesions), bacterial colonization, patients' opinion of seborrhea levels, two objective measurements of sebum levels (Sebutape and Bentonite clay), qualitative assessment of sebum using high power, thin layer chromatography, and biopsies to assess size and configuration of sebaceous glands.
Trials Yield Significant Improvement Results of the first trial in which low doses of isotretinoin were used revealed significant improvements in all parameters tested. Numbers of follicular filaments, and lesions dropped, as did levels of bacteria and sebum. Sebaceous glands shrank, as well.
At the end of the second study, which investigated ultra-low doses of isotretinoin, efficacy was maintained on many of the parameters. There were significant reductions in numbers of active lesions and follicular filaments as well as objective measures of sebum levels. Patients' ratings of seborrhea improved, and levels of P. acnes on the skin diminished.
"The endpoint or the lowest point of a retinoid being effective for the treatment of seborrhea, persistent low grade acne, or maintenance therapy for patients with bad acne probably is around 2.5 mg or 2 mg, or maybe even 1.5 mg," Dr. Plewig said.
The best candidates for low and ultra-low doses isotretinoin therapy, Dr. Plewig said, include patients with severe acne who were controlled with higher doses and require a lower-dose maintenance therapy, individuals whose facial acne has persisted from adolescence into adulthood, and people with sebaceous gland hyperplasia. "Some patients come only because of their oiliness. ... For these patients, I think the low or ultra-low dose is very good, and it's cheap, too," he said.
Severe Patients Still Receive Low Doses Dr. Plewig keeps doses of isotretinoin relatively low in patients with severe acne. "I pretreat patients with severe inflammatory acne with systemic corticosteroids to begin with...about 1 mg/kg body weight for about seven to 14 days, taper it off, and then give an antibiotic, usually an erythromycin, a macrolide," he said. "And then I start with the isotretinoin [0.2 mg/kg to 0.4 mg/kg body weight]. It is so much better. We used to start immediately with isotretinoin or tried antibiotics, but often it takes too long, the patients are miserable, and it is so much better for them because you can have a faster final result, a better final result with cooling down the skin first, then adding your active treatment."
Continuous Use Offers Versatility A great benefit of using lower doses of isotretinoin is that it can be used continuously. There are other important advantages, as well. "In terms of pharmacoeconomics, it is cheaper to use lower doses, it is better tolerated by patients, has fewer side effects, fewer laboratory abnormalities, and of course the patients like it when they have continuous elegant treatment," Dr. Plewig said.
Despite the safer side-effect profile with low-dose isotretinoin, Dr. Plewig emphasized that, at any dose, the drug should still be considered teratogenic and be used with great caution in women of childbearing age.
http://www.dermatologytimes.com/dermatolog...il.jsp?id=65528
Prof. Dr. Dr. h. c. G. Plewig
Klinik und Poliklinik ;>für Dermatologie und Allergologie
Ludwig-Maximilians-Universität München
Frauenlobstra*e 9 – 11
D-80337 München, Germany
Tel.: +49-89-51 60 60 00
Fax: +49-89-51 60 60 02
E-mail:
Gerd.Plewig@;derma.med.uni-muenchen.de
Background: Excessive seborrhea, coarse-pored skin, minimal acne and oily scalp hair comprise a well-known clinical entity. It causes considerable concern, has social impact, and affects the quality of life in some individuals. Some patients seek treatment for seborrhea. No effective topical sebosuppressive medication is available. Oral isotretinoin is the only remedy for men. In women, oral isotretinoin is the most effective remedy, followed by antiandrogens.
Patients and methods: Eleven patients in three groups were treated for 6 months with very low dose isotretinoin. The influence on seborrhea was measured during oral treatment with 5 mg/d, 2.5 mg/d, or 2.5 mg 3× weekly.
Results: Sebum production, measured with Sebutape®, was reduced by up to 64 %. Acne lesions regressed by as much as 84 %. Follicular filaments were reduced by 66 %. Microcomedones were reduced on average up to 86 %. Quantitative bacteriology showed a reduction of Propionibacterium acnes but no increase of Staphylococcus epidermidis. Biopsies revealed a 51 % reduction in sebaceous gland size. With Bentonite™, a reduction of lipids was demonstrated with 2.5 and 5 mg isotretinoin/d but not with 2.5 mg 3× weekly. There was a shift within the lipid fractions: triglycerides dominated, followed by squalenes and free fatty acids.
Conclusions: Good results were achieved in all patients. The small number of patients did not permit a statistical analysis of the three isotretinoin doses studied, but there was a tendency toward better results with the two higher doses.
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