Introduction Atopic dermatitis (AD) is the most common inflammatory skin disorder. Despite the high disease burden, the therapeutic options are limited and their efficacy in controlling AD might be partially satisfactory. Areas Covered Most of the key mediators in AD pathogenesis act through the JAK/STAT signaling pathway, which represents a valid therapeutic target. The first generation of JAK inhibitors, namely tofacitinib and ruxolitinib, inhibit multiple JAKs, whereas newer JAK inhibitors show more selective inhibitory effects for specific JAKs. The aim of this review was to discuss the role of the JAK/STAT pathway in AD and its inhibition, with a special focus on pharmacodynamic properties. Expert opinion JAK inhibitors have different selectivity for various JAK molecules, which influences their pharmacodynamics, efficacy, and safety profile. Since many key cytokines in AD signal through JAK1, the selective JAK1 inhibition may be effective, avoiding the concomitant inhibition of JAK2- and JAK3-dependent pathways could be associated with additional safety issues. Therefore, selective JAK1 inhibitors may represent promising therapeutic agents for AD, as they might prevent off-target effects of JAK inhibitors, especially related to the hematologic profile.

Calabrese, L., Chiricozzi, A., De Simone, C., Fossati, B., D'amore, A., Peris, K., Pharmacodynamics of Janus kinase inhibitors for the treatment of atopic dermatitis, <<EXPERT OPINION ON DRUG METABOLISM &amp; TOXICOLOGY>>, 2022; 18 (5): 347-355. [doi:10.1080/17425255.2022.2099835] [http://hdl.handle.net/10807/214084]

Pharmacodynamics of Janus kinase inhibitors for the treatment of atopic dermatitis

Calabrese, Laura;Chiricozzi, Andrea;De Simone, Clara;Fossati, Barbara;Peris, Ketty
2022

Abstract

Introduction Atopic dermatitis (AD) is the most common inflammatory skin disorder. Despite the high disease burden, the therapeutic options are limited and their efficacy in controlling AD might be partially satisfactory. Areas Covered Most of the key mediators in AD pathogenesis act through the JAK/STAT signaling pathway, which represents a valid therapeutic target. The first generation of JAK inhibitors, namely tofacitinib and ruxolitinib, inhibit multiple JAKs, whereas newer JAK inhibitors show more selective inhibitory effects for specific JAKs. The aim of this review was to discuss the role of the JAK/STAT pathway in AD and its inhibition, with a special focus on pharmacodynamic properties. Expert opinion JAK inhibitors have different selectivity for various JAK molecules, which influences their pharmacodynamics, efficacy, and safety profile. Since many key cytokines in AD signal through JAK1, the selective JAK1 inhibition may be effective, avoiding the concomitant inhibition of JAK2- and JAK3-dependent pathways could be associated with additional safety issues. Therefore, selective JAK1 inhibitors may represent promising therapeutic agents for AD, as they might prevent off-target effects of JAK inhibitors, especially related to the hematologic profile.
Inglese
Calabrese, L., Chiricozzi, A., De Simone, C., Fossati, B., D'amore, A., Peris, K., Pharmacodynamics of Janus kinase inhibitors for the treatment of atopic dermatitis, <<EXPERT OPINION ON DRUG METABOLISM &amp; TOXICOLOGY>>, 2022; 18 (5): 347-355. [doi:10.1080/17425255.2022.2099835] [http://hdl.handle.net/10807/214084]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/214084
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact