Exploring Newer Topical Therapies for Inflammatory Skin Diseases: A Guide for Rheumatologists
DOI:
https://doi.org/10.58931/crt.2024.1249Abstract
Understanding the pathogenesis of many inflammatory skin diseases and their associated signalling pathways has revealed multiple promising therapeutic targets. Given the chronic nature of many of these conditions, products with long-term safety and efficacy are desired. While topical corticosteroids have been the mainstay of topical therapies for years, they are burdened by concerns over long-term safety (i.e., atrophy, striae, telangiectasias), risk of absorption with systemic glucocorticoid side effects, and patient apprehension regarding steroid use. Similarly, topical calcipotriol and retinoids may be ineffective and can cause irritation. Although topical calcineurin inhibitors (i.e., pimecrolimus, tacrolimus) have been approved for atopic dermatitis, their off-label use for many inflammatory conditions may be limited by tolerability issues such as stinging and burning, and lack of effectiveness. The emergence of newer targeted small molecules for topical application, including topical phosphodiesterase-4 inhibitors (PDE4i), topical Janus kinase inhibitors (JAKi), and a therapeutic aryl hydrocarbon modulating agent (TAMA), offer promising new options and will be reviewed here and summarized in Table 1.
References
Bäumer W, Hoppmann J, Rundfeldt C, Keitzmann M. Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007;6(1):17-26. doi: 10.2174/18715280778007731 DOI: https://doi.org/10.2174/187152807780077318
Crowley EL, Gooderham MJ, Phosphodiesterase-4 Inhibition in the management of Psoriasis. Pharmaceutics. 2023;16(1):23. https://doi.org/10.3390/pharmaceutics16010023 DOI: https://doi.org/10.3390/pharmaceutics16010023
Otezla [package insert]. Mississauga (ON): Amgen Canada Inc; 2020. [Cited 2024 Jun 10]. Available from: https://pdf.hres.ca/dpd_pm/00054839.PDF
Eucrisa [package insert]. Kirkland (QC): Pfizer Canada ULC; 2021.[Cited 2024 Jun 10]. Available from: https://pdf.hres.ca/dpd_pm/00060960.PDF
Zoryve [package insert]. Westlake Village (CA): Arcutis Biotherapeutics Inc.; 2023. [Revised 2024 Jan]. [Cited 2024 Jun 10]. Available from: https://www.arcutis.com/wp-content/uploads/USPI-roflumilast-cream.pdf
Lebwohl MG, Kircik LH, Moore AY, Stein Gold L, Draelos ZD, Gooderham MJ, et al. Effect of roflumilast cream vs vehicle cream on chronic plaque psoriasis. JAMA. 2022;328(11):1073. https://doi.org/10.1001/jama.2022.15632 DOI: https://doi.org/10.1001/jama.2022.15632
Zirwas MJ, Draelos ZD, DuBois J, Kircik LH, Moore AY, Gold LS, et al. Efficacy of roflumilast foam, 0.3%, in patients with seborrheic dermatitis: a double-blind, vehicle-controlled phase 2a randomized clinical trial. JAMA Dermatol. 2023;159(6):613–620. doi:10.1001/jamadermatol.2023.0846 DOI: https://doi.org/10.1001/jamadermatol.2023.0846
Gooderham M, Kircik L, Zirwas M, Lee M, Kempers S, Draelos Z, et al. The safety and efficacy of roflumilast cream 0.15% and 0.05% in patients with atopic dermatitis: randomized, double-blind, phase 2 proof of concept study. J Drugs Dermatol. 2023;22(2):139-147. doi:10.36849/JDD.7295 . DOI: https://doi.org/10.36849/JDD.7295
Kontzias A, Kotlyar A, Laurence A, Changelian P, O’Shea JJ. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012;12(4):464-470. doi:10.1016/j.coph.2012.06.008 DOI: https://doi.org/10.1016/j.coph.2012.06.008
Opzelura [package insert]. Wilmington (DE): Incyte Corporation; 2022. [Cited 10 Jun 2024]. Available from: https://www.opzelura.com/opzelura-prescribing-information
Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LE, Leung DYM, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85(4):863-872. doi:10.1016/j.jaad.2021.04.085 DOI: https://doi.org/10.1016/j.jaad.2021.04.085
Rosmarin D, Passeron T, Pandya AG, Grimes P, Harris JE, Desai SR, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387(16):1445–1455. https://doi.org/10.1056/nejmoa2118828 DOI: https://doi.org/10.1056/NEJMoa2118828
Corectim Ointment 0.5% [package insert]. Tokyo, Japan: Japan Tobacco Inc.; 2019. [Cited 2024 Jun 10]. Available from: https://www.torii.co.jp/en/release/2021/20210526_E1.pdf
Bissonnette R, Warren R, Stingeni L, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: results of the Phase 3 DELTA 1 trial. Presented at: Late Breaking Research: presentation on 18 March 2023 at the 81st Annual Meeting of the American Academy of Dermatology (AAD) in New Orleans, LA, USA DOI: https://doi.org/10.1016/j.jaad.2024.07.152
Schliemann S, Pinter A, Schutterlaar ML, et al. Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: results of the Phase 3 DELTA 2 trial. Poster presentation at: The 32nd Annual Congress of the EADV, 11-14 October 2023. Berlin, Germany
Gooderham M, Molin S, Bissonnette R, et al. Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with chronic hand eczema: results of the Phase 3 open-label extension DELTA 3 trial. Presented at: Late Breaking Research: Session 1. 9 March 2024. The 82nd Annual Meeting of the American Academy of Dermatology (AAD), in San Diego, CA, USA DOI: https://doi.org/10.1093/bjd/ljae266.034
Bissonnette R, Stein Gold L, Rubenstein, DS, Tallman AM, Armstrong A. Tapinarof in the treatment of psoriasis: a review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor–modulating agent. J Am Acad Dermatol. 2021;84(4):1059-1067. doi:10.1016/j.jaad.2020.10.085 DOI: https://doi.org/10.1016/j.jaad.2020.10.085
Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, et al. Phase 3 trials of tapinarof cream for plaque psoriasis. N Engl J Med. 2021;385(24):2219-2229.doi: 10.1056/NEJMoa2103629 DOI: https://doi.org/10.1056/NEJMoa2103629
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