Novel topical and systemic therapies in atopic dermatitis

Figures & data

Table 1. A summary of novel topical treatments for atopic dermatitis.

Agent	Target	Drug	Phase	Manufacturer	References
Crisaborole	PDE4	Topical PDE4 inhibitor	Phase III published	Pfizer, New York, NY	[29]
OPA15406	PDE4	Topical PDE4 inhibitor	Phase II published	Otsuka, Tokyo, Japan	[30]
Tofacitinib	JAK1/3	Topical JAK1/3 inhibitor	Phase II published	Innovaderm, Montreal, Quebec, Canada	[31]
JTE-052	JAK	Topical JAK inhibitor	Phase II published	Japan Tobacco Inc, Tokyo, Japan	[32]
Tapinarof	AhR	AhR modulating agent	Phase II published	GlaxoSmithKline, London, UK	[33]
PAC-14028	TRPV1	Topical TRPV1 antagonist	Phase II published	Amorepacific Corporation, Yongin, Korea	[34]

AhR: aryl hydrocarbon receptor; JAK: Janus kinase; PDE4: phosphodiesterase type 4; TRPV1: transient receptor potential vanilloid subfamily, member 1.

Table 2. A summary of novel systemic treatments for atopic dermatitis.

Agent	Target	Drug	Phase	Manufacturer	References
Dupilumab	IL-4Rα	Anti-IL-4Rα mAb	Phase III published	Regeneron, Tarrytown, NY	[35,36]
Lebrikizumab	IL-13	Anti-IL-13 mAb	Phase II published	Hoffmann-La Roche, Basel, Switzerland	[37]
Tralokinumab	IL-13	Anti-IL-13 mAb	Phase II published	MedImmune, Gaithersburg, MD	[38]
Nemolizumab	IL-31R	Anti-IL-31R mAb	Phase II published	Chugai, Tokyo, Japan	[39,40]
Ustekinumab	IL-12/23p40	Anti-p40 mAb	Phase II published	Janssen, Titusville, NJ	[41,42]
Apremilast	PDE4	PDE4 inhibitor: oral small molecule	Phase II published	Celgene, Summit, NJ	[43]
Fezakinumab	IL-22	Anti-IL-22 mAb	Phase II published	Pfizer, New York, NY	[44]
GBR830	OX40	Anti-OX40 mAb	Phase II published	Glenmark, Mumbai, India	[45]
Baricitinib	JAK1/2	JAK1/2 inhibitor: oral small molecule	Phase II published	Eli Lilly, Indianapolis, IN	[46]
ASN002	JAK/SYK	JAK/SYK inhibitor	Phase I published	Asana BioSciences, Bridgewater, NJ	[47]
ZPL-3893787	H4R	H4R antagonist	Phase II published	Ziarco Pharma, Sandwich, UK	[48]
Tezepelumab	TSLP	Anti-TSLP mAb	Phase II published	Amgen, Thousand Oaks, CA	[49]

H4R: histamine 4 receptor; IL-4R: IL-4 receptor; IL-31R: IL-31 receptor; JAK: Janus kinase; mAb: monoclonal antibody; PDE4: phosphodiesterase type 4; SYK: spleen tyrosine kinase; TSLP: thymic stromal lymphopoietin.

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Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175:902–911.

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Nakagawa H, Nemoto O, Igarashi A, et al. Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: a phase II, multicentre, randomized, vehicle-controlled clinical study. Br J Dermatol. 2018;178:424–432.

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Peppers J, Paller AS, Maeda-Chubachi T, 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.e83.

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Lee YW, Won CH, Jung K, et al. Efficacy and safety of PAC-14028 cream - a novel, topical, nonsteroidal, selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial. Br J Dermatol. 2019;180:1030–1038.

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Simpson EL, Flohr C, Eichenfield LF, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78:863–871.e811.

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Wollenberg A, Howell MD, Guttman-Yassky E, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019;143:135–141.

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Ruzicka T, Hanifin JM, Furue M, et al. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376:826–835.

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Kabashima K, Furue M, Hanifin JM, et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: randomized, phase II, long-term extension study. J Allergy Clin Immunol. 2018;142:1121–1130.e1127.

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Saeki H, Kabashima K, Tokura Y, et al. Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol. 2017;177:419–427.

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Khattri S, Brunner PM, Garcet S, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26:28–35.

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Simpson EL, Imafuku S, Poulin Y, et al. A phase 2 randomized trial of apremilast in patients with atopic dermatitis. J Invest Dermatol. 2019;139:1063–1072.

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Guttman-Yassky E, Brunner PM, Neumann AU, et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial. J Am Acad Dermatol. 2018;78:872–881.e876.

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Guttman-Yassky E, Pavel AB, Zhou L, et al. GBR830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J Allergy Clin Immunol. 2019.

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Guttman-Yassky E, Silverberg JI, Nemoto O, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. 2019;80:913–921.e919.

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Bissonnette R, Maari C, Forman S, et al. The Oral JAK/SYK inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: results from a randomised, double-blind, placebo-controlled study. Br J Dermatol. 2019.

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Werfel T, Layton G, Yeadon M, et al. Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143:1830–1837.

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Simpson EL, Parnes JR, She D, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80:1013–1021.

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