Itch and Janus Kinase Inhibitors
DOI:
https://doi.org/10.2340/actadv.v103.5346Keywords:
atopic dermatitis, itch, Janus kinase inhibitors, pruritus, psoriasisAbstract
Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors.
Downloads
References
Yosipovitch G, Rosen JD, Hashimoto T. Itch: from mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol 2018; 142: 1375-1390.
https://doi.org/10.1016/j.jaci.2018.09.005 DOI: https://doi.org/10.1016/j.jaci.2018.09.005
O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The jaK-STAT pathway: impact on human disease and therapeutic intervention. Ann Rev Med 2015; 66: 311-328.
https://doi.org/10.1146/annurev-med-051113-024537 DOI: https://doi.org/10.1146/annurev-med-051113-024537
Chapman S, Kwa M, Gold LS, Lim HW. Janus kinase inhibitors in dermatology: Part I. A comprehensive review. J Am Acad Dermatol 2022; 86: 406-413.
https://doi.org/10.1016/j.jaad.2021.07.002 DOI: https://doi.org/10.1016/j.jaad.2021.07.002
Al-Mashdali AF, Kashgary WR, Yassin MA. Ruxolitinib (a JAK2 inhibitor) as an emerging therapy for refractory pruritus in a patient with low-risk polycythemia vera: a case report. Medicine (Baltimore) 2021; 100: e27722.
https://doi.org/10.1097/MD.0000000000027722 DOI: https://doi.org/10.1097/MD.0000000000027722
Sutaria N, Adawi W, Goldberg R, Roh YS, Choi J, Kwatra SG. Itch: pathogenesis and treatment. J Am Acad Dermatol 2022; 86: 17-34.
https://doi.org/10.1016/j.jaad.2021.07.078 DOI: https://doi.org/10.1016/j.jaad.2021.07.078
Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell 2017; 171: 217-228.
https://doi.org/10.1016/j.cell.2017.08.006 DOI: https://doi.org/10.1016/j.cell.2017.08.006
Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol 2017; 139: S65-76.
https://doi.org/10.1016/j.jaci.2017.01.011 DOI: https://doi.org/10.1016/j.jaci.2017.01.011
Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol 2018; 121: 340-347.
https://doi.org/10.1016/j.anai.2018.07.006 DOI: https://doi.org/10.1016/j.anai.2018.07.006
Amano W, Nakajima S, Kunugi H, Numata Y, Kitoh A, Egawa G, et al. The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. J Allergy Clin Immunol 2015; 136: 667-677.
https://doi.org/10.1016/j.jaci.2015.03.051 DOI: https://doi.org/10.1016/j.jaci.2015.03.051
Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol 2016; 175: 902-911.
https://doi.org/10.1111/bjd.14871 DOI: https://doi.org/10.1111/bjd.14871
Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung DYM, 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; 85: 863-872.
https://doi.org/10.1016/j.jaad.2021.04.085 DOI: https://doi.org/10.1016/j.jaad.2021.04.085
Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. 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 (published correction appears in J Am Acad Dermatol. 2021 Oct; 85: 1069). J Am Acad Dermatol 2020; 82: 823-831.
https://doi.org/10.1016/j.jaad.2019.12.015 DOI: https://doi.org/10.1016/j.jaad.2019.12.015
Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kabashima K, Oda M, et al. Delgocitinib ointment in pediatric patients with atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study. J Am Acad Dermatol 2021; 85: 854-862.
https://doi.org/10.1016/j.jaad.2021.06.014 DOI: https://doi.org/10.1016/j.jaad.2021.06.014
Landis MN, Arya M, Smith S, Draelos Z, Usdan L, Tarabar S, et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group. Br J Dermatol 2022; 187: 878-887.
https://doi.org/10.1111/bjd.21826 DOI: https://doi.org/10.1111/bjd.21826
Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol 2020; 183: 242-255.
https://doi.org/10.1111/bjd.18898 DOI: https://doi.org/10.1111/bjd.18898
Guttman-Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, 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 (published correction appears in Lancet 2021 Jun 5; 397(10290): 2150). Lancet 2021; 397: 2151-2168.
https://doi.org/10.1016/S0140-6736(21)00588-2 DOI: https://doi.org/10.1016/S0140-6736(21)00588-2
Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol 2020; 156: 863-873.
https://doi.org/10.1001/jamadermatol.2020.1406 DOI: https://doi.org/10.1001/jamadermatol.2020.1406
Silverberg JI, Hong HC, Thyssen JP, Calimlim BM, Joshi A, Teixeira HD, et al. Comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis without topical corticosteroids: systematic review and network meta-analysis. Dermatol Ther 2022; 12: 1181-1196.
https://doi.org/10.1007/s13555-022-00721-1 DOI: https://doi.org/10.1007/s13555-022-00721-1
Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De Bruin-Weller M, Barbarot S, et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial (published correction appears in JAMA Dermatol 2022 Feb 1; 158: 219). JAMA Dermatol 2021; 157: 1047-1055.
https://doi.org/10.1001/jamadermatol.2021.3023 DOI: https://doi.org/10.1001/jamadermatol.2021.3023
Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med 2021; 384: 1101-1112.
https://doi.org/10.1056/NEJMoa2019380 DOI: https://doi.org/10.1056/NEJMoa2019380
Bos JD, De Rie MA. The pathogenesis of psoriasis: immunological facts and speculations. Immunol Today 1999; 20: 40-46.
https://doi.org/10.1016/S0167-5699(98)01381-4 DOI: https://doi.org/10.1016/S0167-5699(98)01381-4
Yosipovitch G, Goon A, Wee J, Chan YH, Goh CL. The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. Br J Dermatol 2000; 143: 969-973.
https://doi.org/10.1046/j.1365-2133.2000.03829.x DOI: https://doi.org/10.1046/j.1365-2133.2000.03829.x
Reich A, Szepietowski JC. Mediators of pruritus in psoriasis. Mediators Inflamm 2007; 2007: 64727.
https://doi.org/10.1155/2007/64727 DOI: https://doi.org/10.1155/2007/64727
Papp KA, Bissonnette R, Gooderham M, Feldman SR, Iversen L, Soung J, et al. Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a Phase 2b randomized clinical trial. BMC Dermatol 2016; 16: 15.
https://doi.org/10.1186/s12895-016-0051-4 DOI: https://doi.org/10.1186/s12895-016-0051-4
Punwani N, Burn T, Scherle P, Flores R, Shi J, Collier P, et al. Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor. Br J Dermatol 2015; 173: 989-997.
https://doi.org/10.1111/bjd.13994 DOI: https://doi.org/10.1111/bjd.13994
Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol 2016; 174: 1266-1276.
https://doi.org/10.1111/bjd.14403 DOI: https://doi.org/10.1111/bjd.14403
Schmieder GJ, Draelos ZD, Pariser DM, Banfield C, Cox L, Hodge M, et al. 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. Br J Dermatol 2018; 179: 54-62.
https://doi.org/10.1111/bjd.16004 DOI: https://doi.org/10.1111/bjd.16004
Ludbrook VJ, Hicks KJ, Hanrott KE, Patel JS, Binks MH, Wyres MR, et al. Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study. Br J Dermatol 2016; 174: 985-995.
https://doi.org/10.1111/bjd.14399 DOI: https://doi.org/10.1111/bjd.14399
Armstrong A, Strober B, Gordon KB, Zhuo J, Becker B, Kisa R, et al. Deucravacitinib improves psoriasis symptoms and signs diary domain scores in patients with moderate to severe plaque psoriasis: results from the phase 3 POETYK PSO-1 and POETYK PSO-2 studies. J Cutan Med 2021; 5: s38.
https://doi.org/10.25251/skin.5.supp.38 DOI: https://doi.org/10.25251/skin.5.supp.38
Wang F, Morris C, Bodet ND, Kim BS. Treatment of refractory chronic pruritus of unknown origin with tofacitinib in patients with rheumatoid arthritis. JAMA Dermatol 2019; 155: 1426-1428.
https://doi.org/10.1001/jamadermatol.2019.2804 DOI: https://doi.org/10.1001/jamadermatol.2019.2804
Kim BS, Berger TG, Yosipovitch G. Chronic pruritus of unknown origin (CPUO): Uniform nomenclature and diagnosis as a pathway to standardized understanding and treatment. J Am Acad Dermatol 2019; 81: 1223-1224.
https://doi.org/10.1016/j.jaad.2019.06.038 DOI: https://doi.org/10.1016/j.jaad.2019.06.038
Efficacy of abrocitinib for reducing pruritus in adults with prurigo nodularis and chronic pruritus of unknown origin. [Accessed 2022 Sept 29]. Available from: https://ClinicalTrials.gov/show/NCT05038982.
Agrawal D, Sardana K, Mathachan SR, Bhardwaj M, Ahuja A, Jain S. A prospective study examining the expression of STAT 1, 3, 6 in prurigo nodularis lesions with its immunopathogenic and therapeutic implications. J Cosmet Dermatol 2022; 21: 4009-4015.
https://doi.org/10.1111/jocd.14709 DOI: https://doi.org/10.1111/jocd.14709
A study to evaluate the efficacy and safety of INCB054707 in participants with prurigo nodularis. [Accessed 2022 Sept 29]. Available from: https://ClinicalTrials.gov/show/NCT05061693.
Ju T, Labib A, Vander Does A, Yosipovitch G. Topical Janus kinase-signal transducers and activators of transcription inhibitor tofacitinib is effective in reducing nonatopic dermatitis chronic itch: a case series. J Am Acad Dermatol 2022; 87: 400-403.
https://doi.org/10.1016/j.jaad.2022.03.012 DOI: https://doi.org/10.1016/j.jaad.2022.03.012
Peng C, Li C, Zhou Y, Wang Q, Xie P, Li T, Hao P. Tofacitinib for prurigo nodularis: a case report. Clin Cosmet Investig Dermatol 2022; 15: 503-506.
https://doi.org/10.2147/CCID.S354025 DOI: https://doi.org/10.2147/CCID.S354025
Shao S, Tsoi LC, Sarkar MK, Xing X, Xue K, Uppala R, et al. IFN-γ enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus. Sci Transl Med 2019; 11: eaav7561.
https://doi.org/10.1126/scitranslmed.aav7561 DOI: https://doi.org/10.1126/scitranslmed.aav7561
Brumfiel CM, Patel MH, Severson KJ, Zhang N, Li X, Quillen JK, et al. Ruxolitinib cream in the treatment of cutaneous lichen planus: a prospective, open-label study. J Invest Dermatol 2022; 142: 2109-2116.e4.
https://doi.org/10.1016/j.jid.2022.01.015 DOI: https://doi.org/10.1016/j.jid.2022.01.015
Seiringer P, Lauffer F, Pilz AC, Boehmer D, Biedermann T, Eyerich K. Tofacitinib in hypertrophic lichen planus. Acta Derm Venereol 2020; 100: adv00220.
https://doi.org/10.2340/00015555-3585 DOI: https://doi.org/10.2340/00015555-3585
Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, et al. 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. J Am Acad Dermatol 2023; 88: 29-39.
https://doi.org/10.1016/j.jaad.2022.07.002 DOI: https://doi.org/10.1016/j.jaad.2022.07.002
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2023 Yujin Han, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
