Janus kinaz (JAK) inhibitörlerinin psöriyazis ve psöriyatik artrit tedavisinde kullanımı

Yıl 2024, Cilt: 4 Sayı: 1, 1 - 9, 30.06.2024

Eslem Altın

Öz

Psöriyazis ve psöriyatik artrit birbirleriyle son derece ilişkili kronik, inflamatuar ve oto-immün rahatsızlıklardır. Plak psöriyazisi ciltte eritematöz pullu plaklar ile karakterize olan bir cilt hastalığıdır. Psöriyatik artrit ise psöriyazis hastalarının 1/3’ünü etkileyen, enflame eklemlerle karakterize romatizmal bir hastalıktır. Psöriyazis ve psöriyatik artrit patogenezindeki bu ortak temelden dolayı, tedavileri ortak bir süreci beraberinde getirebilmektedir. Çeşitli topikal ve sistemik tedaviler psöriyazis ve psöriyatik artitte güncel tedavi yöntemlerini oluşturmaktadır. Ancak bu iki komorbid hastalığın yüksek heterojenitesi ve mevcut tedavilerin dezavantajlarından dolayı alternatif ilaçların keşfi önem arz etmektedir. JAK-STAT (Janus kinase-signal transducer and activator of transcription) önemli inflamatuar süreçlere aracılık eden bir yolaktır ve psöriyazis ve psöriyatik artritte bu sinyal yolağı öncü bir rol oynar. JAK ailesi, JAK-1, JAK-2, JAK-3 ve Tirozin Kinaz-2 (TYK-2) olmak üzere 4 intraselüler üyeden oluşur. JAK inhibitörleri, JAK proteinlerini inhibe ederek yolağın aktivitesini önler. Psöriyazis ve psöriyatik artrit tedavisinde potent terapötikler olması sebebiyle yapılan araştırmalar devam etmektedir. Onaylanan farmasötiklerle bu ilaç grubunun tedavideki önemleri her geçen gün artmaktadır. Bu derlemede, JAK inhibitörlerinin psöriyazis ve psöriyatik artrit tedavisindeki kullanımları hakkında bilgi verilmesi amaçlanmıştır.

Anahtar Kelimeler

Psöriyazis, Psöriyatik artrit, JAK inhibitörleri

Etik Beyan

Çalışma bir derleme yazısıdır, etik beyan sunulmamıştır.

Destekleyen Kurum

Kütahya Sağlık Bilimleri Üniversitesi Tıp Fakültesi

Teşekkür

Danışman hocam Doç. Dr. Ayşe Koçak Sezgin’e teşekkür ederim.

Use of Janus kinase (JAK) inhibitors in the treatment of psoriasis and psoriatic arthritis

Öz

Psoriasis and psoriatic arthritis are chronic, inflammatory and auto-immune disorders that are highly related to each other. Plaque psoriasis is a skin disease, characterized by erythematous scaly plaques on the skin. And psoriatic arthritis is a rheumatic disease that affects 1/3 of psoriasis patients, characterized by inflamed joints. Due to common basis in the pathogenesis of psoriasis and psoriatic arthritis, their treatment can bring a common process. Various topical and systemic treatments are the current treatment methods for psoriasis and psoriatic arthritis. However, because of the high heterogeneity of these two comorbid diseases and the disadvantages of current treatments, the discovery of alternative drugs is important. JAK-STAT (The Janus kinase-signal transducer and activator of transcription) is a pathway that mediates important inflammatory processes and it is believed that this signaling pathway plays a leading role in psoriasis and psoriatic arthritis. The JAK family consists of 4 intracellular members, namely JAK-1, JAK-2, JAK-3 and Tyrosine Kinase-2 (TYK-2). JAK inhibitors prevent the activity of the pathway by inhibiting JAK proteins. They are potent therapeutics for the treatment of psoriasis and psoriatic arthritis, therefore researchs are ongoing. Through approved pharmaceuticals, the importance of this group in treatment is increasing every day. In this review, it was aimed to provide information about the use of JAK inhibitors in the treatment of psoriasis and psoriatic arthritis.

Anahtar Kelimeler

Psoriasis, Psoriatic arthritis, JAK inhibitors

Kaynakça

• Słuczanowska-Głąbowska S, Ziegler-Krawczyk A, Szumilas K, Pawlik A. Role of Janus kinase inhibitors in therapy of psoriasis. J Clin Med. 2021;10:4307.
• WHO. Global Report On Psoriasis: 2016. Geneva, WHO.
• Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140:645-53.
• Sarabia S, Ranjith B, Koppikar S, Wijeratne DT. Efficacy and safety of JAK inhibitors in the treatment of psoriasis and psoriatic arthritis: a systematic review and meta-analysis. BMC Rheumatol. 2022;6:71.
• Martin G. Novel Therapies in Plaque Psoriasis: A Review of Tyrosine kinase 2 inhibitors. Dermatol Ther (Heidelb). 2023;13:417-35.
• Torres T, Filipe P. Small molecules in the treatment of psoriasis. Drug Dev Res. 2015;76:215-27.
• Alpsoy E, Ergun T, Şendur N. Tüm Yönleriyle Psoriasis. Ankara, Türk Dermatoloji Derneği Yayınları. 2020;7.
• Doğan B. Psoriasisde kullanılan tedavi seçenekleri, sistemik tedavi seçenekleri, gelecekteki tedaviler. In Tüm yönleriyle psoriasis (Eds E Alpsoy, T Ergun, N Şendur). Ankara, Türk Dermatoloji Derneği Yayınları. 2020;7.
• Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017;76:736-44.
• Xin P, Xu X, Deng C, Liu S, Wang Y, Zhou X et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol. 2020;80:106210.
• Kvist-Hansen A, Hansen PR, Skov L. Systemic treatment of psoriasis with JAK inhibitors: A review. Dermatol Ther (Heidelb). 2020;10:29-42.
• Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019;20:1475.
• Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D et al. Treatment of plaque psoriasis with deucravacitinib (POETYK PSO-1 study): a plain language summary. Immunotherapy. 2023;15:963-73.
• Mosca M, Hong J, Hadeler E, Hakimi M, Liao W, Bhutani T. The role of IL-17 cytokines in psoriasis. Immunotargets Ther. 2021;10:409-18.
• Ocampo DV, Gladman D. Psoriatic arthritis. F1000Res. 2019;8: F1000 Faculty Rev-1665.
• Coates LC, Helliwell PS. Psoriatic arthritis: state of the art review. Clin Med (Lond). 2017;17:65-70.
• Şendur ÖF. Psoriasis ve psoriatik artrit ilişkisi. In Psoriatik Artrit (Ed K Nas):36-41. İstanbul, İstanbul Tıp Kitabevleri, 2021.
• Solmaz, D, Akar S. Psoriatik artritte entezit ve daktilit. In Psoriatik Artrit (Ed K Nas):47-51. İstanbul, İstanbul Tıp Kitabevleri. 2021;47
• Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391:2273-84.
• Kishimoto M, Deshpande GA, Fukuoka K et al. Clinical features of psoriatic arthritis. Best Pract Res Clin Rheumatol. 2021;35:101670.
• Nas K. (Edited by). Psoriatik Artrit. Çevik R, Em S. Psoriatik artritin genetiği. İstanbul Tıp Kitabevleri. 2021;7-14.
• Stober C. Pathogenesis of psoriatic arthritis. Best Pract Res Clin Rheumatol. 2021;35:101694.
• Jamilloux Y, El Jammal T, Vuitton L, Gerfaud-Valentin M, Kerever S, Sève P. JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2019;18:102390.
• Chen M, Dai SM. A novel treatment for psoriatic arthritis: Janus kinase inhibitors. Chin Med J (Engl). 2020;133:959-67.
• PubChem. Deucravacitinib.. https://pubchem.ncbi.nlm.nih.gov/ compound/134821691. (Accessed 19.09.2023).
• Estevinho T, Lé AM, Torres T. Deucravacitinib in the treatment of psoriasis. J Dermatolog Treat. 2023;34:2154122.
• Kim, Lori S.; Wu, Jashin J.; Han, George. Deucravacitinib for psoriasis. Curr Derm Rep. 2021;10:1-5.
• Papp K, Gordon K, Thaçi D, Morita A, Goodheram M, Foley P et al. Phase 2 trial of selective Tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379:1313-21.
• Armstrong A, Gooderham M, Warren RB, Papp K, Strober B, Thaçi D et al. Pos1042 efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 (tyk2) inhibitor, compared with placebo and apremilast in moderate to severe plaque psoriasis: results from the phase 3 poetyk pso-1 study. Ann Rheum Dis. 2021;80:795.1–96.
• Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P et al. 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. J Am Acad Dermatol. 2023;88:40-51.
• Aydın F, Şahin G. JAK-STAT inhibitörleri ve dermatolojide kullanımları. Dermatoz. 2018;9.1:1-10.
• Roskoski R Jr. Deucravacitinib is an allosteric TYK2 protein kinase inhibitor FDA-approved for the treatment of psoriasis. Pharmacol Res. 2023;189:106642.
• Azevedo A, Torres T. Tofacitinib: a new oral therapy for psoriasis. Clin Drug Investig. 2018;38:101-12.
• Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167:668-77.
• Mamolo C, Harness J, Tan H, Menter A. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, improves patient-reported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-to-severe psoriasis. J Eur Acad Dermatol Venereol. 2014;28:192-203.
• Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, Langley R et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2015;173:949-61.
• Şentürk N. Tofacitinib. Turkderm-Turk Arch Dermatol Venereol. 2022;56:67-9.
• Zhang J, Qi F, Dong J, Tan Y, Gao L, Liu F. Application of baricitinib in dermatology. J Inflamm Res. 2022;15:1935-41.
• 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;174:1266-76.
• Food and Drug Administration. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022. ( Accesed 17.08.2023).
• Schmieder GJ, Draelos ZD, Pariser DM, Banfield J, 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.
• Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81:815-22.
• PubChem. Upadacitinib. https://pubchem.ncbi.nlm.nih.gov/compound/58557659 (Accessed 20.08.2023).
• Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis. 2021;80:312-20.
• Nash P, Coates LC, Fleischmann R, Fleishmann R, Papp KA, Gómez-Reino JJ et al. Efficacy of tofacitinib for the treatment of psoriatic arthritis: Pooled analysis of two phase 3 studies. Rheumatol Ther. 2018;5:567-82.