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50 Years of Topical Retinoids for Acne: Evolution of Treatment

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Abstract

Since the US Food and Drug Administration (FDA) approved tretinoin in 1971, retinoids alone or combined with other agents have become the mainstay of acne treatment. Retinoids act through binding to retinoic acid receptors, altering expression levels of hundreds of cellular proteins affecting multiple pathways involved in acne pathogenesis. Retinoids have evolved from first-generation agents, such as tretinoin, through chemical modifications resulting in a second generation (etretinate and acitretin for psoriasis), a third generation (adapalene and tazarotene) and, most recently, a fourth (trifarotene). For all topical retinoids, local irritation has been associated with poor tolerability and suboptimal adherence. Efforts to improve tolerability have utilized novel delivery systems and/or novel agents. This qualitative literature review summarizes the evolution of the four topical single-agent retinoids available for the treatment of acne in the US today and their various formulations, presenting the rationale behind their development and data from key studies.

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Fig 1
Fig 2

Adapted from Embil and Nacht, 1996 [64]. Scanning electron micrograph of a microsponge particle approximately 25 microns in diameter (×5000). Inset: The ultrastructure of a fractured microsponge (×6000). b Micronized tretinoin [62]. Cryo scanning electron microscopy imaging of the polymeric matrix (×1000). Micronized tretinoin particles are predominantly < 10 microns in diameter. c Polymeric emulsion (for tazarotene) [70]. Part 1: Cryo-scanning electron microscopy imaging showing oil-in-water emulsion droplet (approximately 1- to 2-micron diameter) separated within a polymeric matrix (×10,000). Part 2: This highly spreadable lotion formulation was developed to allow for even skin distribution and more efficient delivery of tazarotene into dermal layers while reducing the potential for skin irritation

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Acknowledgements

Medical writing support was provided by Robert M. Rydzewski, CMPP and Lynn M. Anderson, PhD (Prescott Medical Communications Group, Chicago, IL, USA) with financial support from Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC.

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Authors and Affiliations

  1. The Acne Treatment and Research Center, Brooklyn, NY, USA

    Hilary Baldwin

  2. Robert Wood Johnson University Hospital, New Brunswick, NJ, USA

    Hilary Baldwin

  3. Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA

    Guy Webster

  4. Henry Ford Hospital, Detroit, MI, USA

    Linda Stein Gold

  5. Callender Dermatology and Cosmetic Center, Glenn Dale, MD, USA

    Valerie Callender

  6. Howard University College of Medicine, Washington D.C., USA

    Valerie Callender

  7. PLLC and Department of Dermatology, Mount Sinai Hospital Center, New York, NY, USA

    Fran E. Cook-Bolden

  8. Ortho Dermatologics, a Division of Bausch Health US, LLC, Bridgewater, NJ, USA

    Eric Guenin

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Correspondence to Hilary Baldwin.

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Medical writing support for this review article was funded by Ortho Dermatologics.

Conflict of Interest

Hilary Baldwin has served as advisor, investigator, and on speakers’ bureaus for Almirall, Cassiopea, Foamix, Galderma, Ortho Dermatologics, Sol Gel, and Sun Pharmaceuticals. Guy Webster has served as a consultant, speaker, or investigator for Ortho Dermatologics, Galderma, Almirall, Foamix Pharmaceuticals, and Sol-Gel Technologies. Linda Stein Gold has served as investigator, consultant, or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharmaceuticals, UCB, Arcutis, and Lilly. Valerie Callender has served as an investigator, consultant, or speaker for Allergan, Galderma, L’Oréal, and Ortho Dermatologics. Fran E. Cook-Bolden has served as consultant, speaker, or investigator for Galderma, LEO Pharma, Almirall, Cassiopea, Ortho Dermatologics, Investigators Encore, Foamix Pharmaceuticals, Hovione, Aclaris, and Cutanea. Eric Guenin is an employee of Ortho Dermatologics and may hold stock and/or stock options in its parent company.

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Baldwin, H., Webster, G., Stein Gold, L. et al. 50 Years of Topical Retinoids for Acne: Evolution of Treatment. Am J Clin Dermatol 22, 315–327 (2021). https://doi.org/10.1007/s40257-021-00594-8

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