: Tyrosine kinase 2 (TYK2) inhibition has recently emerged as a novel therapeutic strategy in dermatology, targeting key cytokine pathways involved in immune-mediated inflammatory diseases. Deucravacitinib, an oral, selective TYK2 inhibitor that binds the regulatory pseudokinase domain, modulates signalling mediated by IL-12, IL-23 and type I interferons whilst sparing the broader JAK family, thereby providing targeted immunomodulation with a potentially improved safety profile compared with conventional JAK inhibitors. Pivotal randomized clinical trials have demonstrated robust efficacy and sustained responses in moderate-to-severe plaque psoriasis and psoriatic arthritis, establishing deucravacitinib as an effective systemic therapeutic option. However, clinical trials only partially capture the complexity of cases encountered in routine dermatological practice. In this context, this narrative review summarizes the current clinical evidence on deucravacitinib in dermatology, with a particular focus on real-world data and emerging off-label applications. Real-world studies in psoriasis consistently confirm rapid clinical improvement, durable responses and favourable tolerability across heterogeneous patient populations, including individuals with prior biologic exposure and those with involvement of difficult-to-treat areas such as the scalp, nails, palms and soles. Beyond psoriasis, an expanding body of evidence from case series and observational reports suggests potential therapeutic benefits of TYK2 inhibition in several inflammatory and autoimmune dermatological conditions, including cutaneous lupus erythematosus, dermatomyositis, alopecia areata, lichen planus, granuloma annulare, pityriasis rubra pilaris, overlapping psoriasis/eczema and cutaneous sarcoidosis. These observations highlight the broad immunomodulatory potential of TYK2 inhibition across diverse cytokine-driven pathways implicated in dermatological diseases. Although current evidence outside psoriasis remains limited and largely derived from small case series, the accumulating clinical experience suggests that deucravacitinib may represent a versatile therapeutic option in patients with refractory or complex disease phenotypes. Ongoing clinical trials and future real- world studies will be crucial to better define the long-term efficacy, safety and optimal therapeutic positioning of deucravacitinib across the spectrum of dermatological disorders.
Deucravacitinib in dermatology: current indication and existing off-label data / D'Agostino, M., Potestio, L., Tommasino, N., Megna, M.. - In: DRUGS IN CONTEXT. - ISSN 1740-4398. - 15:(2026), pp. 1-26. [10.7573/dic.2026-4-1]
Deucravacitinib in dermatology: current indication and existing off-label data
D'Agostino, Michela;Potestio, Luca;Tommasino, Nello;Megna, Matteo
2026
Abstract
: Tyrosine kinase 2 (TYK2) inhibition has recently emerged as a novel therapeutic strategy in dermatology, targeting key cytokine pathways involved in immune-mediated inflammatory diseases. Deucravacitinib, an oral, selective TYK2 inhibitor that binds the regulatory pseudokinase domain, modulates signalling mediated by IL-12, IL-23 and type I interferons whilst sparing the broader JAK family, thereby providing targeted immunomodulation with a potentially improved safety profile compared with conventional JAK inhibitors. Pivotal randomized clinical trials have demonstrated robust efficacy and sustained responses in moderate-to-severe plaque psoriasis and psoriatic arthritis, establishing deucravacitinib as an effective systemic therapeutic option. However, clinical trials only partially capture the complexity of cases encountered in routine dermatological practice. In this context, this narrative review summarizes the current clinical evidence on deucravacitinib in dermatology, with a particular focus on real-world data and emerging off-label applications. Real-world studies in psoriasis consistently confirm rapid clinical improvement, durable responses and favourable tolerability across heterogeneous patient populations, including individuals with prior biologic exposure and those with involvement of difficult-to-treat areas such as the scalp, nails, palms and soles. Beyond psoriasis, an expanding body of evidence from case series and observational reports suggests potential therapeutic benefits of TYK2 inhibition in several inflammatory and autoimmune dermatological conditions, including cutaneous lupus erythematosus, dermatomyositis, alopecia areata, lichen planus, granuloma annulare, pityriasis rubra pilaris, overlapping psoriasis/eczema and cutaneous sarcoidosis. These observations highlight the broad immunomodulatory potential of TYK2 inhibition across diverse cytokine-driven pathways implicated in dermatological diseases. Although current evidence outside psoriasis remains limited and largely derived from small case series, the accumulating clinical experience suggests that deucravacitinib may represent a versatile therapeutic option in patients with refractory or complex disease phenotypes. Ongoing clinical trials and future real- world studies will be crucial to better define the long-term efficacy, safety and optimal therapeutic positioning of deucravacitinib across the spectrum of dermatological disorders.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.


