Vestnik dermatologii i venerologiiVestnik dermatologii i venerologiiВестник дерматологии и венерологии0042-46092313-6294Rossijskoe Obschestvo Dermatovenerologov i Kosmetologov1692510.25208/vdv16925seqiqoREVIEWSОБЗОР ЛИТЕРАТУРЫReview ArticleSystematization of the two-decade world experience using tacrolimus ointment off-label. Fundamental information on the product, its use in vitiligo and fibrosing connective tissue diseasesСистематизация мирового опыта двух десятилетий применения мази такролимуса по незарегистрированным показаниям (off-label). Фундаментальные сведения о препарате, применение при витилиго и фиброзирующих заболеваниях соединительной тканиhttps://orcid.org/0000-0002-6309-70441315-4785PetruninDmitry D.ПетрунинДмитрий Дмитриевич
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н.

prof.preobrazhenskii@gmail.comLEO Pharmaсeutical Products LLC«ЛЕО Фармасьютикал Продактс»25112025131220251015Vestnik dermatologii i venerologiiВестник дерматологии и венерологии45572107202528102025Copyright ©; 2025, Petrunin D.D.Copyright ©; 2025, Петрунин Д.Д.2025Petrunin D.D.Петрунин Д.Д.https://creativecommons.org/licenses/by-nc/4.0https://vestnikdv.ru/jour/article/view/16925

Developed in the 1990s and introduced into clinical practice in the first decade of the 21st century, tacrolimus ointment (known worldwide under the trade name Protopic®) became the first and most potent member of the class of topical calcineurin inhibitors (TCIs) and the first alternative to topical glucocorticosteroids (TGCs) in terms of its anti-inflammatory activity in half a century. Its unique mechanism of action (selective T-cell immunosuppressant) and the absence of side effects typical of TGCs have made it a valuable tool in the therapeutic arsenal of dermatologists. Today, tacrolimus ointment is included in all possible international and national clinical guidelines for the treatment of atopic dermatitis, which is the only registered indication, and has the highest level of evidence (1A). Unfortunately, for a number of reasons, mostly commercial in nature, the manufacturer did not invest in a clinical trial program that would have allowed the registration of tacrolimus ointment for other indications. However, it is clear that the T-cell immune response plays a crucial role in pathogenesis of a wide range of dermatoses, and the pharmacodynamics of tacrolimus are well-suited for their treatment. In this regard, over the past two decades, hundreds of clinical studies have been conducted by independent investigators including well-designed double-blind randomized studies that have provided the evidence base for including tacrolimus ointment in the clinical guidelines for a wide range of off-label indications. The purpose of this review is to systematize the aforementioned global experience in order to raise awareness of clinicians and make more rational practical use of the valuable clinical tool, that is tacrolimus ointment. The first part of this review (the second part will be published later) provides general information on tacrolimus ointment including the history of its development, pharmacological characteristics and clinical applications as well as addressing off-label drug use. The evidence base for the use of tacrolimus ointment in the treatment of vitiligo and fibrosing connective tissue diseases will be analyzed.

Созданный в 1990-е годы и вошедший в клиническую практику в первой декаде XXI в. препарат такролимуса в форме мази (известен во всех странах под торговым названием Протопик®) стал первым и наиболее активным представителем класса топических ингибиторов кальциневрина (ТИК) и первой за полвека альтернативой топическим глюкокортикостероидам (ТГКС) по своей противовоспалительной активности. Уникальный механизм действия (селективный Т-клеточный иммуносупрессант) и отсутствие характерных для ТГКС побочных эффектов сделали его ценным инструментом в терапевтическом арсенале дерматологов. На сегодняшний день мазь такролимуса входит во все возможные международные и национальные клинические рекомендации по лечению атопического дерматита, являющегося единственным зарегистрированным показанием к применению, имея наивысший уровень доказательности (1А). К сожалению, по ряду причин, преимущественно коммерческого характера, компания-производитель не стала инвестировать в программу клинических испытаний, которые позволили бы зарегистрировать мазь такролимуса по другим показаниям; в то же время очевидно, что Т-клеточный иммунный ответ играет ключевую роль в патогенезе широкого спектра дерматозов и фармакодинамика такролимуса полностью отвечает задаче их лечения. В связи с этим за два минувших десятилетия независимыми исследователями были проведены сотни клинических исследований, включая высокодоказательные двойные слепые рандомизированные, обеспечившие доказательную базу, которая позволила включить мазь такролимуса в клинические рекомендации по широкому спектру незарегистрированных показаний. Цель данного обзора — систематизация упомянутого мирового опыта для повышения осведомленности о нем клиницистов и более рационального практического использования ценного клинического инструмента, коим является мазь такролимуса. В первой части данного обзора (вторая будет опубликована позднее) приведены общие сведения о мази такролимуса, включая историю разработки, фармакологические характеристики и особенности клинического применения, а также затронута проблема off-label применения препаратов. Будет проанализирована доказательная база по применению мази такролимуса для лечения витилиго и фиброзирующих заболеваний соединительной ткани.

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