Systematization of the two-decade world experience using tacrolimus ointment off-label. Fundamental information on the product, its use in vitiligo and fibrosing connective tissue diseases

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Abstract

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.

About the authors

Dmitry D. Petrunin

LEO Pharmaсeutical Products LLC

Author for correspondence.
Email: prof.preobrazhenskii@gmail.com
ORCID iD: 0000-0002-6309-7044
SPIN-code: 1315-4785

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

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