40 years’ experience of using isotretinoin in treatment of acne: efficacy, optimal dosage, relapses

Objective — to analyze domestic and foreign literature sources on the use of systemic isotretinoin (SI) in the treatment of acne, focus on aspects of the evolution of the isotretinoin molecule, new routes of action and dosing regimens of the drug, the effectiveness of therapy, relapses and prognostic factors of their development. Materials and methods. We conducted the analysis of publications (systematic reviews, clinical trials and observational studies) from the databases of the Vernadskyi National Library of Ukraine, PubMed, MEDLINE, Web of Science and Scopus by June 2023. The search criteria were the words «acne», «systemic therapy», «isotretinoin», «isotre­tinoin-LIDOSE», «mechanism of action», «efficacy», «daily dose», «cumulative dose», «relapses» and their analogues in the English language. The final choice of 60 sources was based on the author’s judgments about their completeness and significance for solving the goals. Results and discussion. The clinical efficacy of SI is due to its powerful effect on the leading links of the pathogenesis: hyperproliferation of follicular keratinocytes, hyperactivity of sebocytes, excessive colonization of Cutibacterium acnes and immune-mediated inflammation. A comparative analysis of two forms of SI existing in Ukraine was carried out, the advan­tages of isotretinoin-LIDOSE over standard isotretinoin in clinical practice were determined. It is not possible to draw a clear conclusion about the indications for SI use in acne because there are conflicting recommendations in national guidelines (USA, UK, Canada) and the international consensus of the Global Alliance. At present, in addition to the standard daily doses of SI, a number of regimens have been proposed in the treatment of moderate and mild acne, suggesting a certain reduction in the corresponding doses that decreases the risk of side effects and has sufficient therapeutic efficacy. The advantages and disadvantages of standard, high-dose and low-dose isotretin regimens are described in terms of effectiveness, duration of remission, and relapse rate. Conclusions. Isotretinoin has a high profile of clinical efficacy. It is a treatment for severe and moderate forms of acne that provides a stable therapeutic effect at standard (0.5—1 mg/kg/day) or high doses (more than 1 mg/kg/day). The treatment of acne of moderate and mild severity with low daily doses of SI (less than 0.5 mg/kg) leads to the preservation of the effectiveness of therapy while improving tolerability and reducing the possible risk of side effects. It was determined that the rate of regression of clinical manifestations of acne does not depend on the daily dose (low, standard, high), but the frequency of relapses increases in patients who received low doses. The effectiveness of treatment is higher with the use of fixed (daily) standard, low or high doses of SI compared with intermittent use (every other day, 1 week or 10 days per month). Achieving a cumulative dose (120 to 150 mg/kg) is supported by clinical studies, consensus and dermatological practice. The duration of therapy with standard doses is 16—24 weeks, in the low-dose regimen — for a long time (more than 8 months). It is determined individually until a clinical effect is achieved. In cases of earlier regression of acne manifestations, when patients have not reached the cumulative dose, treatment with SI should be continued until complete regression of the rash and for the following 4—8 weeks. The use of isotretinoin-LIDOSE due to extrabioavailability, high solubility, independence from food intake allows obtaining better clinical results and improving compliance in the treatment of acne patients.