Dupilumab
Dupilumab, a monoclonal antibody against interleukin-4 receptor alpha, was established as a treatment for atopic dermatitis via two randomised, placebo-controlled phase 3 trials (SOLO1 and SOLO2) and is approved for this indication.[51]Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016 Dec 15;375(24):2335-48.
https://www.nejm.org/doi/10.1056/NEJMoa1610020
http://www.ncbi.nlm.nih.gov/pubmed/27690741?tool=bestpractice.com
[52]Ho JSS, Molin S. A review of existing and new treatments for the management of hand eczema. J Cutan Med Surg. 2023 Sep-Oct;27(5):493-503.
https://journals.sagepub.com/doi/10.1177/12034754231188325
http://www.ncbi.nlm.nih.gov/pubmed/37496489?tool=bestpractice.com
Its use for chronic hand eczema, including vesicular subtypes, has been studied in phase 2b and observational trials where subjects achieved clinical and symptomatic improvement.[53]Voorberg AN, Romeijn GLE, de Bruin-Weller MS, et al. The long-term effect of dupilumab on chronic hand eczema in patients with moderate to severe atopic dermatitis-52 week results from the Dutch BioDay Registry. Contact Dermatitis. 2022 Aug;87(2):185-91.
https://onlinelibrary.wiley.com/doi/10.1111/cod.14104
http://www.ncbi.nlm.nih.gov/pubmed/35279856?tool=bestpractice.com
[54]Voorberg AN, Kamphuis E, Christoffers WA, et al. Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin: a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study. Br J Dermatol. 2023 Sep 15;189(4):400-9.
https://academic.oup.com/bjd/article/189/4/400/7160661
http://www.ncbi.nlm.nih.gov/pubmed/37170922?tool=bestpractice.com
There have also been published case reports and case series of successful use of dupilumab in dyshidrotic eczema.[55]Oosterhaven JAF, Romeijn GLE, Schuttelaar MLA. Dupilumab treatment of very severe refractory atopic hand eczema. JAMA Dermatol. 2018 Aug 1;154(8):969-70.
https://jamanetwork.com/journals/jamadermatology/article-abstract/2686153
http://www.ncbi.nlm.nih.gov/pubmed/29971331?tool=bestpractice.com
[56]Cheng J, Facheris P, Ungar B, et al. Current emerging and investigational drugs for the treatment of chronic hand eczema. Expert Opin Investig Drugs. 2022 Aug;31(8):843-53.
https://www.doi.org/10.1080/13543784.2022.2087059
http://www.ncbi.nlm.nih.gov/pubmed/35658708?tool=bestpractice.com
[57]Deng L, Luo Y, An B, et al. Recalcitrant palmar-plantar atopic dermatitis successfully treated with dupilumab: a case series. Clin Cosmet Investig Dermatol. 2022;15:2421-26.
https://www.dovepress.com/recalcitrant-palmar-plantar-atopic-dermatitis-successfully-treated-wit-peer-reviewed-fulltext-article-CCID
http://www.ncbi.nlm.nih.gov/pubmed/36387965?tool=bestpractice.com
Janus kinase (JAK) inhibitors
The small molecule JAK inhibitors encompass a class of newer topical and oral medicines directed towards the JAK/STAT signalling pathway which are implicated in several inflammatory diseases including dermatitis.[52]Ho JSS, Molin S. A review of existing and new treatments for the management of hand eczema. J Cutan Med Surg. 2023 Sep-Oct;27(5):493-503.
https://journals.sagepub.com/doi/10.1177/12034754231188325
http://www.ncbi.nlm.nih.gov/pubmed/37496489?tool=bestpractice.com
Topical JAK inhibitors such as ruxolitinib, tofacitinib, and delgocitinib have demonstrated benefit in atopic dermatitis in phase 2 and 3 trials.[58]Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016 Nov;175(5):902-11.
https://academic.oup.com/bjd/article/175/5/902/6697102
http://www.ncbi.nlm.nih.gov/pubmed/27423107?tool=bestpractice.com
[59]Nakagawa H, Nemoto O, Igarashi A, et al. 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 Apr;82(4):823-31.
https://www.doi.org/10.1016/j.jaad.2019.12.015
http://www.ncbi.nlm.nih.gov/pubmed/32029304?tool=bestpractice.com
Topical ruxolitinib is approved for atopic dermatitis and was studied for hand eczema.[60]Papp K, Szepietowski JC, Kircik L, 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 Oct;85(4):863-72.
https://linkinghub.elsevier.com/retrieve/pii/S0190962221009312
http://www.ncbi.nlm.nih.gov/pubmed/33957195?tool=bestpractice.com
The oral JAK inhibitors abrocitinib, upadacitinib, and baricitinib have randomised, controlled, clinical trial evidence for efficacy and treatment of atopic dermatitis with upadacitinib currently being studied for hand eczema.[61]Reich K, Thyssen JP, Blauvelt A, et al. Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial. Lancet. 2022 Jul 23;400(10348):273-82.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01199-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35871814?tool=bestpractice.com
[62]Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021 Mar 25;384(12):1101-12.
https://www.nejm.org/doi/10.1056/NEJMoa2019380
http://www.ncbi.nlm.nih.gov/pubmed/33761207?tool=bestpractice.com
[63]Shi VY, Bhutani T, Fonacier L, et al. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J Am Acad Dermatol. 2022 Aug;87(2):351-58.
https://www.jaad.org/article/S0190-9622(22)00608-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/35439608?tool=bestpractice.com
[64]Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020 Jul 25;396(10246):255-66.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30732-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32711801?tool=bestpractice.com
[65]Silverberg JI, Simpson EL, Thyssen JP, et al. Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020 Aug 1;156(8):863-73.
https://jamanetwork.com/journals/jamadermatology/fullarticle/2766772
http://www.ncbi.nlm.nih.gov/pubmed/32492087?tool=bestpractice.com
[66]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 Apr;80(4):913-21.e9.
https://www.jaad.org/article/S0190-9622(18)30129-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29410014?tool=bestpractice.com
[67]Bieber T, Reich K, Paul C, et al. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol. 2022 Sep;187(3):338-52.
https://academic.oup.com/bjd/article/187/3/338/6966588
http://www.ncbi.nlm.nih.gov/pubmed/35484697?tool=bestpractice.com
[68]Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021 Jun 5;397(10290):2151-68.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00588-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34023008?tool=bestpractice.com
[69]Reich K, Teixeira HD, de Bruin-Weller M, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021 Jun 5;397(10290):2169-81.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00589-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34023009?tool=bestpractice.com
There is a case report of treatment success with the upadacitinib for dyshidrotic eczema.[70]Kiszla BM, Orlowski TJ, Kole LCS. Efficacy and tolerance of upadacitinib in the treatment of dyshidrotic eczema. JAAD Case Rep. 2023 Aug;38:141-43.
https://www.jaadcasereports.org/article/S2352-5126(23)00219-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37521189?tool=bestpractice.com
Crisaborole
Crisaborole is a topical phosphodiesterase-4 inhibitor that is approved for atopic dermatitis, based on two large double blinded vehicle-controlled studies.[71]Paller AS, Tom WL, Lebwohl MG, 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 Sep;75(3):494-503.e6.
https://www.jaad.org/article/S0190-9622(16)30330-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27417017?tool=bestpractice.com
[72]Chu DK, Chu AWL, Rayner DG, et al. Topical treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials. J Allergy Clin Immunol. 2023 Sep 5;:.
https://www.doi.org/10.1016/j.jaci.2023.08.030
http://www.ncbi.nlm.nih.gov/pubmed/37678572?tool=bestpractice.com
Although it has not been studied specifically in dyshidrotic eczema, it has shown some efficacy in hand dermatitis in a single institution case series.[73]Kahn JS, Grossman-Kranseler JS, Zancanaro P, et al. Topical crisaborole in the treatment of atopic hand dermatitis: a retrospective chart review. Dermatitis. 2021 Nov-Dec 01;32(6):e141-43.
https://www.doi.org/10.1097/DER.0000000000000793
http://www.ncbi.nlm.nih.gov/pubmed/34570730?tool=bestpractice.com