What’s New in Topicals for Atopic Dermatitis?

Chiesa Fuxench ZC, Block JK, Boguniewicz M, Boyle J, Fonacier L, Gelfand JM, et al. Atopic dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139(3):583–90. https://doi.org/10.1016/j.jid.2018.08.028.

CAS  Article  PubMed  Google Scholar 

Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131(1):67–73. https://doi.org/10.1038/jid.2010.251.

CAS  Article  PubMed  Google Scholar 

Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483–94. https://doi.org/10.1056/nejmra074081.

CAS  Article  PubMed  Google Scholar 

Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116–132. https://doi.org/10.1016/j.jaad.2014.03.023

Charman CR, Morris AD, Williams HC. Topical corticosteroid phobia in patients with atopic eczema. Br J Dermatol. 2000;142(5):931–6. https://doi.org/10.1046/j.1365-2133.2000.03473.x.

CAS  Article  PubMed  Google Scholar 

Niemeier V, Kupfer J, Schill WB, Gieler U. Atopic dermatitis—topical therapy: do patients apply much too little? J Dermatol Treat. 2005;16(2):95–101. https://doi.org/10.1080/09546630510027895.

CAS  Article  Google Scholar 

Asgari MM, Tsai AL, Avalos L, Sokil M, Quesenberry CP Jr. Association between topical calcineurin inhibitor use and keratinocyte carcinoma risk among adults with atopic dermatitis. JAMA Dermatol. 2020;156(10):1066–73. https://doi.org/10.1001/jamadermatol.2020.2240.

Article  PubMed  Google Scholar 

Paller AS, Fölster-Holst R, Chen SC, Diepgen TL, Elmets C, Margolis DJ, et al. No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis. J Am Acad Dermatol. 2020;83(2):375–81. https://doi.org/10.1016/j.jaad.2020.03.075.

CAS  Article  PubMed  Google Scholar 

Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503.e6. https://doi.org/10.1016/j.jaad.2016.05.046.

CAS  Article  PubMed  Google Scholar 

Grewe SR, Chan SC, Hanifin JM. Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness. J Allergy Clin Immunol. 1982;70(6):452–7. https://doi.org/10.1016/0091-6749(82)90008-2.

CAS  Article  PubMed  Google Scholar 

Schlessinger J, Shepard JS, Gower R, Su JC, Lynde C, Cha A, et al. Safety, effectiveness, and pharmacokinetics of crisaborole in infants aged 3 to < 24 months with mild-to-moderate atopic dermatitis: a phase IV open-label study (CrisADe CARE 1). Am J Clin Dermatol. 2020;21(2):275–84. https://doi.org/10.1007/s40257-020-00510-6.

Article  PubMed  PubMed Central  Google Scholar 

Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2(3): e24137. https://doi.org/10.4161/jkst.24137.

Article  PubMed  PubMed Central  Google Scholar 

Chovatiya R, Paller AS. JAK inhibitors in the treatment of atopic dermatitis. J Allergy Clin Immunol. 2021;148(4):927–40. https://doi.org/10.1016/j.jaci.2021.08.009.

CAS  Article  PubMed  Google Scholar 

O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72 Suppl 2(0 2):ii111–ii115. https://doi.org/10.1136/annrheumdis-2012-202576

Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease [published online ahead of print]. Nat Rev Drug Discov. 2021;1–20. https://doi.org/10.1038/s41573-021-00266-6

Prescribing information for opzelura (ruxolitinib) cream 1.5%; Revised 2021 Sept [cited 2022 Feb 13]; https://www.opzelura.com/prescribing-information.pdf

Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung D, 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):863–72. https://doi.org/10.1016/j.jaad.2021.04.085.

CAS  Article  PubMed  Google Scholar 

Gong X, Chen X, Kuligowski ME, Liu X, Liu X, Cimino E, et al. Pharmacokinetics of ruxolitinib in patients with atopic dermatitis treated with ruxolitinib cream: data from phase II and III studies. Am J Clin Dermatol. 2021;22(4):555–66. https://doi.org/10.1007/s40257-021-00610-x.

Article  PubMed  PubMed Central  Google Scholar 

Blauvelt A, Szepietowski JC, Papp K, et al. Ruxolitinib cream rapidly decreases pruritus in atopic dermatitis: pooled results from two phase 3 studies. Presented at: AAD VMX 2021; April 23–26, 2021. Poster 26884.

Eichenfield LF, Simpson EL, Siegfried EC, et al. Efficacy and safety of ruxolitinib cream among adolescents with atopic dermatitis: pooled results from two phase 3 studies. Presented at: AAD VMX 2021; April 23–26, 2021. Poster 27633.

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82(4):823–31. https://doi.org/10.1016/j.jaad.2019.12.015.

CAS  Article  PubMed  Google Scholar 

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Murata R, Kaino H, et al. Long-term safety and efficacy of delgocitinib ointment, a topical janus kinase inhibitor, in adult patients with atopic dermatitis. J Dermatol. 2020;47(2):114–20. https://doi.org/10.1111/1346-8138.15173.

CAS  Article  PubMed  Google Scholar 

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kabashima K, Oda M, et al. Delgocitinib ointment in pediatric patients with atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study. J Am Acad Dermatol. 2021;85(4):854–62. https://doi.org/10.1016/j.jaad.2021.06.014.

CAS  Article  PubMed  Google Scholar 

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Oda M, Kabashima K, et al. Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis [published correction appears in J Allergy Clin Immunol. 2021 Oct;148(4):1088]. J Allergy Clin Immunol. 2019;144(6):1575–1583. https://doi.org/10.1016/j.jaci.2019.08.004

Worm M, Bauer A, Elsner P, Mahler V, Molin S, Nielsen TSS. Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study. Br J Dermatol. 2020;182(5):1103–10. https://doi.org/10.1111/bjd.18469.

CAS  Article  PubMed  Google Scholar 

Worm M, Thyssen JP, Schliemann S, Bauer A, Shi VY, Ehst B, et al. The topical pan-JAK inhibitor delgocitinib cream demonstrates dose response in a 16-week phase 2b trial in chronic hand eczema. D1T03.4A, EADV 2020 Virtual Congress, 29–31 Oct.

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT04872101, Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 2); 2021 May 4 [cited 2022 Feb 13]; https://clinicaltrials.gov/ct2/show/NCT04872101

Li H, Zuo J, Tang W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front Pharmacol. 2018;9:1048. https://doi.org/10.3389/fphar.2018.01048.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Schafer PH, Truzzi F, Parton A, Wu L, Kosek J, Zhang LH, et al. Phosphodiesterase 4 in inflammatory diseases: effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. Cell Signal. 2016;28(7):753–63. https://doi.org/10.1016/j.cellsig.2016.01.007.

CAS  Article  PubMed  Google Scholar 

Zebda R, Paller AS. Phosphodiesterase 4 inhibitors. J Am Acad Dermatol. 2018;78(3):S43–52. https://doi.org/10.1016/j.jaad.2017.11.056.

CAS  Article  PubMed  Google Scholar 

Schlessinger J, Shepard JS, Gower R, Su JC, Lynde C, Cha A, et al. Safety, Effectiveness, and pharmacokinetics of crisaborole in infantsa aged 3 to < 24 months with mild-to-moderate atopic dermatitis: a phase IV open-label study (CrisADe CARE 1). Am J Clin Dermatol. 2020;21(2):275–84. https://doi.org/10.1007/s40257-020-00510-6.

Article  PubMed  PubMed Central  Google Scholar 

Gooderham MJ, Kircik LH, Zirwas M, Lee M, Kempers SE, Draelos ZD, et al. The safety and efficacy of roflumilast cream 0.15% and 0.05% in atopic dermatitis: phase 2 proof-of-concept study. Br J Dermatol. 2021;184:e56–e87. https://doi.org/10.1111/bjd.19722

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT04773587, Trial of PDE4 inhibition with roflumilast for the management of atopic dermatitis (INTEGUMENT-I); 2021 Feb 26 [cited 2022 Feb 13]; https://clinicaltrials.gov/ct2/show/NCT04773587?term=roflumilast&cond=atopic+dermatitis&draw=2&rank=3

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT04773600, Trial of PDE4 inhibition with roflumilast for the management of atopic dermatitis (INTEGUMENT-II); 2021 Feb 26 [cited 2022 Feb 13]; https://clinicaltrials.gov/ct2/show/NCT04773600?term=roflumilast&cond=atopic+dermatitis&draw=1&rank=4

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT04845620, Trial of PDE4 inhibition with roflumilast for the management of atopic dermatitis (INTEGUMENT-PED); 2021 April 15 [cited 2022 Feb 13]; https://clinicaltrials.gov/ct2/show/NCT04845620?term=roflumilast&cond=atopic+dermatitis&draw=1&rank=5

Saeki H, Ito K, Yokota D, Tsubouchi H. Difamilast ointment in adult patients with atopic dermatitis: a phase 3 randomized double-blind vehicle-controlled trial. J Am Acad Dermatol. 2021;S0190–9622(21):02682–7. https://doi.org/10.1016/j.jaad.2021.10.027.

CAS  Article  Google Scholar 

Saeki H, Baba N, Ito K, Yokota D, Tsubouchi H. Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial. Br J Dermatol. 2021. https://doi.org/10.1111/bjd.20655.

Article  PubMed  PubMed Central  Google Scholar 

Otsuka Pharmaceutical Co., Ltd. [Internet]. Otsuka's moizerto® ointment granted approval in japan as a treatment for atopic dermatitis; 2021 Sept 27 [cited 2022 Feb 13]; https://www.otsuka.co.jp/en/company/newsreleases/2021/20210927_1.html

Chieosilapatham P, Kiatsurayanon C, Umehara Y, Trujillo-Paez JV, Peng G, Yue H, et al. Keratinocytes: innate immune cells in atopic dermatitis. Clin Exp Immunol. 2021;204(3):296–309. https://doi.org/10.1111/cei.13575.

CAS  Article  PubMed  PubMed Central  Google Scholar 

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):1059–67. https://doi.org/10.1016/j.jaad.2020.10.085.

CAS  Article  PubMed  Google Scholar 

Furue M, Hashimoto-Hachiya A, Tsuji G. Aryl hydrocarbon receptor in atopic dermatitis and psoriasis. Int J Mol Sci. 2019;20(21):5424. https://doi.org/10.3390/ijms20215424.

CAS  Article  PubMed Central  Google Scholar 

Furue M. Regulation of filaggrin, loricrin, and involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: pathogenic implications in atopic dermatitis. Int J Mol Sci. 2020;21(15):5382. https://doi.org/10.3390/ijms21155382.

CAS  Article  PubMed Central  Google Scholar 

Peppers J, Paller AS, Maeda-Chubachi T, Wu S, Robbins K, Gallagher K, et al. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019;80:89–98. https://doi.org/10.1016/j.jaad.2018.06.047.

CAS  Article  PubMed  Google Scholar 

Paller AS, Stein Gold L, Soung J, Tallman AM, Rubenstein DS, Gooderham M. Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis. J Am Acad Dermatol. 2021;84(3):632–8. https://doi.org/10.1016/j.jaad.2020.05.135.

CAS  Article  PubMed  Google Scholar 

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT05014568, Tapinarof for the treatment of atop

留言 (0)

沒有登入
gif