{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:26:18Z","timestamp":1789147578282,"version":"build-2803163510"},"reference-count":90,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Psoriasis is an inflammatory skin disease with a chronic relapsing course and an often-detrimental impact on patients\u2019 quality of life. Thanks to incredible advances in research over the past few decades, the therapeutic armamentarium of psoriasis is now reasonably broad and structured, with several therapeutic agents that have demonstrated successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of existing ones. A great deal of attention has recently been paid to the JAK\/STAT pathway, playing a crucial role in chronic inflammatory skin diseases, including psoriasis. Indeed, in a disease with such a complex pathogenesis, the possibility to antagonize multiple molecular pathways via JAK\/STAT inhibition offers an undeniable therapeutic advantage. However, data from clinical trials evaluating the use of oral JAK inhibitors in immune-mediated disorders, such as RA, have arisen safety concerns, suggesting a potentially increased risk of class-specific AEs such as infections, venous thromboembolism, and malignancies. New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis.<\/jats:p>","DOI":"10.3390\/jcm13113091","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T09:33:31Z","timestamp":1716802411000},"page":"3091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic Potential of Targeting the JAK\/STAT Pathway in Psoriasis: Focus on TYK2 Inhibition"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9441-3923","authenticated-orcid":false,"given":"Martina","family":"Dragotto","sequence":"first","affiliation":[{"name":"Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8315-3413","authenticated-orcid":false,"given":"Martina","family":"D\u2019Onghia","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-9206","authenticated-orcid":false,"given":"Emanuele","family":"Trovato","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-4310","authenticated-orcid":false,"given":"Linda","family":"Tognetti","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Rubegni","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5238-2336","authenticated-orcid":false,"given":"Laura","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, 53100 Siena, Italy"},{"name":"Institute of Dermatology, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1075","DOI":"10.1111\/jdv.19117","article-title":"Real-life effectiveness of Risankizumab according to body mass index: Results of an Italian multicentre retrospective study","volume":"37","author":"Dragotto","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1001\/jamadermatol.2021.2007","article-title":"Psoriasis Prevalence in Adults in the United States","volume":"157","author":"Armstrong","year":"2021","journal-title":"JAMA Dermatol."},{"key":"ref_3","first-page":"1","article-title":"Prevalence of skin diseases in a population; a census study from the faroe islands","volume":"11","author":"Lomholt","year":"1964","journal-title":"Dan Med. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ii18","DOI":"10.1136\/ard.2004.033217","article-title":"Psoriasis: Epidemiology, clinical features, and quality of life","volume":"64","author":"Langley","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1365-2133.2009.09593.x","article-title":"Epidemiology and comorbidity of psoriasis in children","volume":"162","author":"Augustin","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","author":"Boehncke","year":"2015","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1365-2133.2006.07675.x","article-title":"A classification of psoriasis vulgaris according to phenotype","volume":"156","author":"Griffiths","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1136\/bmj.3.5768.231","article-title":"Psoriasis\u2014Clinical features","volume":"3","author":"Baker","year":"1971","journal-title":"Br. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gisondi, P., Bellinato, F., and Girolomoni, G. (2020). Topographic Differential Diagnosis of Chronic Plaque Psoriasis: Challenges and Tricks. J. Clin. Med., 9.","DOI":"10.3390\/jcm9113594"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1590\/abd1806-4841.20164288","article-title":"Geographic tongue and psoriasis: Clinical, histopathological, immunohistochemical and genetic correlation\u2014A literature review","volume":"91","author":"Picciani","year":"2016","journal-title":"An. Bras. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/S0140-6736(18)30830-4","article-title":"The pathogenesis of psoriatic arthritis","volume":"391","author":"Veale","year":"2018","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"D\u2019onghia, M., Ursini, F., Cinotti, E., Calabrese, L., Tognetti, L., Cartocci, A., Lazzeri, L., Frediani, B., Rubegni, P., and Trovato, E. (2024). Psoriasis and Fibromyalgia: A Systematic Review. J. Pers. Med., 14.","DOI":"10.3390\/jpm14020165"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1080\/14712598.2022.2093106","article-title":"Place in therapy of anti-IL-17 and 23 in psoriasis according to the severity of comorbidities: A focus on cardiovascular disease and metabolic syndrome","volume":"22","author":"Trovato","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ii65","DOI":"10.1136\/ard.2004.031237","article-title":"Psoriasis assessment tools in clinical trials","volume":"64","author":"Feldman","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gisondi, P., Del Giglio, M., and Girolomoni, G. (2017). Treatment Approaches to Moderate to Severe Psoriasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112427"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/ijd.16917","article-title":"Drug survival of biologics and non-biologics in patients affected by palmoplantar psoriasis: A \u00abreal-world\u00bb, mono-center experience","volume":"63","author":"Caldarola","year":"2024","journal-title":"Int. J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1080\/13543784.2023.2184684","article-title":"Investigational systemic drugs for moderate to severe plaque psoriasis: What\u2019s new?","volume":"32","author":"Calabrese","year":"2023","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lee, H.J., and Kim, M. (2023). Challenges and Future Trends in the Treatment of Psoriasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713313"},{"key":"ref_20","first-page":"411","article-title":"New JAK inhibitors for the treatment of psoriasis and psoriatic arthritis","volume":"155","author":"Chiricozzi","year":"2020","journal-title":"G. Ital. Dermatol. Venereol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1080\/13543784.2020.1800639","article-title":"Baricitinib: Therapeutic potential for moderate to severe atopic dermatitis","volume":"29","author":"Calabrese","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/17425255.2022.2099835","article-title":"Pharmacodynamics of Janus kinase inhibitors for the treatment of atopic dermatitis","volume":"18","author":"Calabrese","year":"2022","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rendon, A., and Sch\u00e4kel, K. (2019). Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061475"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0738-081X(95)93817-8","article-title":"Altered keratinocyte growth and differentiation in psoriasis","volume":"13","author":"McKay","year":"1995","journal-title":"Clin. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1365-2613.2009.00669.x","article-title":"Angiogenesis drives psoriasis pathogenesis","volume":"90","author":"Heidenreich","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1016\/j.jaad.2005.10.057","article-title":"Innate and adaptive immunity and the pathophysiology of psoriasis","volume":"54","author":"Gaspari","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/jdv.14433","article-title":"The role of IL-23 and the IL-23\/TH 17 immune axis in the pathogenesis and treatment of psoriasis","volume":"31","author":"Girolomoni","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ni.2366","article-title":"IL-12 family cytokines: Immunological playmakers","volume":"13","author":"Vignali","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ng.311","article-title":"Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways","volume":"41","author":"Nair","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1084\/jem.20050500","article-title":"Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production","volume":"202","author":"Nestle","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1080\/17460441.2023.2246880","article-title":"The preclinical discovery and development of deucravacitinib for the treatment of psoriasis","volume":"18","author":"Coscarella","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nri1001","article-title":"Interleukin-12 and the regulation of innate resistance and adaptive immunity","volume":"3","author":"Trinchieri","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.3389\/fimmu.2018.01210","article-title":"Transcription Factor Retinoid-Related Orphan Receptor \u03b3t: A Promising Target for the Treatment of Psoriasis","volume":"9","author":"Tang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/S0140-6736(21)00184-7","article-title":"Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis","volume":"397","author":"Ghoreschi","year":"2021","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Harrison, D.A. (2012). The Jak\/STAT pathway. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a011205"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-065X.2008.00754.x","article-title":"Janus kinases in immune cell signaling","volume":"228","author":"Ghoreschi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Diop, A., Santorelli, D., Malagrin\u00f2, F., Nardella, C., Pennacchietti, V., Pagano, L., Marcocci, L., Pietrangeli, P., Gianni, S., and Toto, A. (2022). SH2 Domains: Folding, Binding and Therapeutical Approaches. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415944"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/pro.3519","article-title":"The molecular details of cytokine signaling via the JAK\/STAT pathway","volume":"27","author":"Morris","year":"2018","journal-title":"Protein Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41392-023-01655-6","article-title":"Signaling pathways and targeted therapies for psoriasis","volume":"8","author":"Guo","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jaad.2021.06.869","article-title":"Tyrosine kinase 2 and Janus kinase\u2013signal transducer and activator of transcription signaling and inhibition in plaque psoriasis","volume":"86","author":"Krueger","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rusi\u00f1ol, L., and Puig, L. (2023). Tyk2 Targeting in Immune-Mediated Inflammatory Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043391"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4331\/wjbc.v13.i1.1","article-title":"Current understanding of the role of tyrosine kinase 2 signaling in immune responses","volume":"13","author":"Muromoto","year":"2022","journal-title":"World J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.4049\/jimmunol.1202859","article-title":"A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors","volume":"191","author":"Sohn","year":"2013","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20140712","article-title":"The molecular regulation of Janus kinase (JAK) activation","volume":"462","author":"Babon","year":"2014","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1074-7613(00)00054-6","article-title":"Partial impairment of cytokine responses in Tyk2-deficient mice","volume":"13","author":"Karaghiosoff","year":"2000","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Karjalainen, A., Shoebridge, S., Krunic, M., Simonovi\u0107, N., Tebb, G., Macho-Maschler, S., Strobl, B., and M\u00fcller, M. (2020). TYK2 in Tumor Immunosurveillance. Cancers, 12.","DOI":"10.3390\/cancers12010150"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/emboj\/cdg038","article-title":"The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression","volume":"22","author":"Ragimbeau","year":"2003","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s40265-020-01261-8","article-title":"JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors","volume":"80","author":"Nogueira","year":"2020","journal-title":"Drugs"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5373","DOI":"10.2147\/JIR.S380686","article-title":"TYK2 in Immune Responses and Treatment of Psoriasis","volume":"15","author":"Shang","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0140-6736(21)00438-4","article-title":"Current and future status of JAK inhibitors","volume":"398","author":"McLornan","year":"2021","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2147\/CCID.S433367","article-title":"JAK Inhibitors in Psoriatic Disease","volume":"16","author":"Megna","year":"2023","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3109\/09546634.2015.1115819","article-title":"A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis","volume":"27","author":"Bissonnette","year":"2016","journal-title":"J. Dermatolog. Treat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/bjd.16004","article-title":"Efficacy and safety of the Janus kinase 1 inhibitor PF-04965842 in patients with moderate-to-severe psoriasis: Phase II, randomized, double-blind, placebo-controlled study","volume":"179","author":"Schmieder","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/bjd.14399","article-title":"Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study","volume":"174","author":"Ludbrook","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1016\/S0140-6736(18)32483-8","article-title":"Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): Results from a randomised, placebo-controlled, phase 2 trial","volume":"392","author":"Mease","year":"2018","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/bjd.14403","article-title":"A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1\/JAK2 inhibitor, in patients with moderate-to-severe psoriasis","volume":"174","author":"Papp","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jaad.2018.04.018","article-title":"Topical Janus kinase inhibitors: A review of applications in dermatology","volume":"79","author":"Hosking","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/bjd.13745","article-title":"A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis","volume":"173","author":"Papp","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1056\/NEJMoa1615977","article-title":"Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors","volume":"377","author":"Gladman","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1056\/NEJMoa1615975","article-title":"Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis","volume":"377","author":"Mease","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s40744-020-00209-4","article-title":"Safety and Efficacy of Tofacitinib in Patients with Active Psoriatic Arthritis: Interim Analysis of OPAL Balance, an Open-Label, Long-Term Extension Study","volume":"7","author":"Nash","year":"2020","journal-title":"Rheumatol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/bjd.14018","article-title":"Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Results from two randomized, placebo-controlled, phase III trials","volume":"173","author":"Papp","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0140-6736(14)62113-9","article-title":"Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: A phase 3 randomised non-inferiority trial","volume":"386","author":"Bachelez","year":"2015","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.jaci.2015.12.1318","article-title":"Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study","volume":"137","author":"Krueger","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1111\/bjd.13551","article-title":"Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: A randomized controlled trial","volume":"172","author":"Bissonnette","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMoa2022516","article-title":"Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis","volume":"384","author":"McInnes","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1136\/annrheumdis-2020-218870","article-title":"Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2","volume":"80","author":"Mease","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/14728214.2020.1745773","article-title":"Emerging systemic drugs in the treatment of plaque psoriasis","volume":"25","author":"Balogh","year":"2020","journal-title":"Expert Opin. Emerg. Drugs."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"eaaw1736","DOI":"10.1126\/scitranslmed.aaw1736","article-title":"Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain","volume":"11","author":"Burke","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11061","DOI":"10.1074\/jbc.M114.619502","article-title":"Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by Pharmacological Stabilization of Its Pseudokinase Domain","volume":"290","author":"Tokarski","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8973","DOI":"10.1021\/acs.jmedchem.9b00444","article-title":"Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165","volume":"62","author":"Wrobleski","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1056\/NEJMoa1806382","article-title":"Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis","volume":"379","author":"Papp","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jaad.2022.07.002","article-title":"Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial","volume":"88","author":"Armstrong","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jaad.2022.08.061","article-title":"Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program for Evaluation of TYK2 inhibitor psoriasis second trial","volume":"88","author":"Strober","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1093\/bjd\/ljae014","article-title":"Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase 3 poetyk trials","volume":"190","author":"Lebwohl","year":"2024","journal-title":"Br. J. Dermatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/1346-8138.16740","article-title":"Efficacy and safety of the selective TYK2 inhibitor, deucravacitinib, in Japanese patients with moderate to severe plaque psoriasis: Subgroup analysis of a randomized, double-blind, placebo-controlled, global phase 3 trial","volume":"50","author":"Imafuku","year":"2023","journal-title":"J. Dermatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/1346-8138.17074","article-title":"Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in Japanese patients with moderate to severe plaque, erythrodermic, or generalized pustular psoriasis: Efficacy and safety results from an open-label, phase 3 trial","volume":"51","author":"Imafuku","year":"2024","journal-title":"J. Dermatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/psp4.13100","article-title":"Population pharmacokinetic modeling of oral brepocitinib in healthy volunteers and patients with immuno-inflammatory diseases","volume":"13","author":"Maleki","year":"2024","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jaad.2021.03.050","article-title":"A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results","volume":"85","author":"King","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"EVIDoa2300155","DOI":"10.1056\/EVIDoa2300155","article-title":"Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa","volume":"3","author":"Kimball","year":"2024","journal-title":"NEJM Evid."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/j.jid.2019.11.027","article-title":"Molecular and Cellular Responses to the TYK2\/JAK1 Inhibitor PF-06700841 Reveal Reduction of Skin Inflammation in Plaque Psoriasis","volume":"140","author":"Page","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/jcph.1046","article-title":"The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a TYK2\/JAK1 Inhibitor (PF-06700841) in Healthy Subjects and Patients With Plaque Psoriasis","volume":"58","author":"Banfield","year":"2018","journal-title":"J. Clin. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1016\/j.jid.2020.03.962","article-title":"TYK2\/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial","volume":"140","author":"Forman","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1002\/art.42519","article-title":"Efficacy and Safety of the TYK2\/JAK1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial","volume":"75","author":"Mease","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/bjd\/ljad098","article-title":"Efficacy and safety of topical brepocitinib cream for mild-to-moderate chronic plaque psoriasis: A phase IIb randomized double-blind vehicle-controlled parallel-group study","volume":"189","author":"Landis","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e204","DOI":"10.1016\/S2665-9913(20)30397-0","article-title":"Safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of the oral TYK2 inhibitor PF-06826647 in participants with plaque psoriasis: A phase 1, randomised, double-blind, placebo-controlled, parallel-group study","volume":"3","author":"Tehlirian","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jaad.2022.03.059","article-title":"Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study","volume":"87","author":"Tehlirian","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/jdv.19426","article-title":"The safety of systemic Janus kinase inhibitors in atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials","volume":"38","author":"Yoon","year":"2024","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2154122","DOI":"10.1080\/09546634.2022.2154122","article-title":"Deucravacitinib in the treatment of psoriasis","volume":"34","author":"Estevinho","year":"2023","journal-title":"J. Dermatolog. Treat."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:48:29Z","timestamp":1760107709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,24]]},"references-count":90,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13113091"],"URL":"https:\/\/doi.org\/10.3390\/jcm13113091","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,24]]}}}