Systemic isotretinoin in modern clinical guidelines on acne management

Abstract

Objective — to analyze the medical and technological documents developed on the basis of evidence­based medicine (guidelines, recommendations, consensuses) regarding the treatment of patients with acne of various degrees of severity with systemic retinoids (systemic isotretinoin preparations) dating from 2013 to 2023, as also to focus attention on the pharmacokinetic features of the original systemic isotretinoin according to innovative Lidose technology. Materials and methods. An analysis was conducted of clinical European guidelines (French guideline and those of the European Dermatology Forum), guidelines of the American Academy of Dermatology, the National Institute for Health Protection and Improvement of Medical Care (NICE) of Great Britain in conjunction with the British Dermatology Association and the Canadian Dermatology Association, recommendations of the American Academy of Pediatrics and the French Society of Dermatology, the International Consensus of the Global Alliance for the Improvement of Acne Treatment Outcomes, and consensus­based practical and daily guideline for the management of acne patients. The key words for the search were «acne», «clinical guideline», «consensus», «systemic treatment», «isotretinoin», «isotretinoin­ Lidose». Results and discussion. Clinical guidelines (2013, 2015, 2016) for the management of acne recommend isotretinoin at a dose of 0.5—1 mg/kg/day for 16—24 weeks to a total (cumulative) dose of 120—150 mg/kg for severe acne (nodular/conglobate acne). Low-­dose regimens of isotretinoin (< 0.5 mg/kg/day) have been used with varying degrees of success in the treatment of severe papulopustular/moderate nodular acnе. The International Consensus of the Global Alliance to Improve Acne Treatment Outcomes (2017) supports standard isotretinoin dosing for severe acne until the cumulative dose is reached. At the same time, for patients that have severe papulopustular acne, poor tolerance, risk of serious side effects, or rash regression before the cumulative dose is achieved it is recommended to continue taking the drug until the skin is completely cleansed of acne­elements and for additional 1—2 months. Such provisions are set out in the guidelines developed jointly with the British Association of Dermatologists (2021). According to the American Academy of Dermatology (2023) guidelines, standard isotretinoin or isotretinoin ­Lidose® is recommended for patients for whom isotretinoin is indicated, which is supported by high­quality evidence. Due to the Lidose technology, the soluble fraction of isotretinoin increases, while the insoluble fraction responsible for side effects, on the contrary, decreases. The bioavailability of the drug increases, which allows lowering the daily and course doses of the drug. Conclusions. Systemic isotretinoin has a convincing evidence base as highly effective treatment for severe and moderate forms of acne, providing a sustained therapeutic effect at standard or low doses. In current US guidelines, isotretinoin and isotretinoin­ Lidose® are recommended for the treatment of severe acne, as well as acne that causes psychosocial burden or scarring, or acne that does not respond to treatment with oral or topical therapy. The use of isotretinoin ­Lidose® due to extrabioavailability, high solubility, independence from food intake allows to obtain better clinical results, has a favorable safety profile, characterized by a minimal frequency of adverse reactions.