{"id":352488,"date":"2023-04-14T00:00:00","date_gmt":"2023-04-13T22:00:00","guid":{"rendered":"https:\/\/medizinonline.com\/?p=352488"},"modified":"2023-02-23T15:02:20","modified_gmt":"2023-02-23T14:02:20","slug":"tyk2-inhibition-shows-great-therapeutic-potential","status":"publish","type":"post","link":"https:\/\/medizinonline.com\/en\/tyk2-inhibition-shows-great-therapeutic-potential\/","title":{"rendered":"TYK2 inhibition shows great therapeutic potential"},"content":{"rendered":"\n

Psoriasis is nowadays understood as a systemic disease, which is based on chronic inflammation. Research into the etiopathogenesis, as well as the establishment of new active substances, is progressing rapidly. A promising new approach is TYK2 inhibition. In pivotal clinical trials, the first oral selective tyrosine kinase 2 inhibitor in psoriasis showed promising results. <\/strong><\/p>\n\n\n\n

For patients with moderate to severe psoriasis, there are many safe and effective biologic therapies available in addition to conventional systemic therapies. However, some patients prefer oral therapeutics [1]. TYK2 inhibition using deucravacitinib (BMS-986165) may fill this therapeutic gap. <\/p>\n\n

Deucravacitinib is a highly selective oral tyrosine kinase 2 inhibitor<\/h3>\n\n

In contrast to inhibitors of JAK1-3, deucravacitinib selectively blocks IL-23, IL-12, and type I IFN signaling by binding to the regulatory domain, but not those of IL-6, hematopoietic growth factors, and the \u03b3c-receptor family (Fig. 1)<\/strong> [2]. Thus, deucravacitinib achieves highly selective effects, which likely contributes to an improved safety profile. <\/p>\n\n

<\/p>\n\n

\"\"<\/a><\/figure>\n\n

In a randomized-controlled double-blind phase II dose-finding study including 267 patients with moderate-to-severe psoriasis, deucravacitinib showed clinical efficacy at a daily dose of 3 mg and higher (NCT02931838) [3]. The proportion of patients with a 75% or greater reduction in PASI at week 12 was significantly higher in patients receiving deucravacitinib than in the placebo group (at 3 mg daily or twice daily, at 6 mg twice daily, and at 12 mg daily) (p<0.001) [3]. <\/p>\n\n

Phase III study program POETYK: promising results <\/h3>\n\n

In the EU, a recommendation of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency is currently under review [4]. The CHMP based its positive opinion on the results of the pivotal Phase III POETYK PSO-1 and POETYK PSO-2 studies, which evaluated once-daily administration of deucravacitinib in patients with moderate-to-severe plaque psoriasis compared to placebo and twice-daily apremilast, as well as additional two-year data from the long-term extension study POETYK PSO. Results from the 52-week, double-blind, phase III POETYK PSO-1 trial (NCT03624127) were published in The Journal of the American Academy of Dermatology<\/em> 2023 [5]. Participants were randomized 2:1:1 to receive either deucravacitinib 6 mg daily (n=332), placebo (n=166), or apremilast 30 mg twice daily (n=168). At week 16, response rates were significantly higher with deucravacitinib than with placebo or apremilast for both PASI 75** (58.4% vs. 12.7% vs. 35.1%; p <0.0001) and sPGA\u00a3<\/sup> 0\/1 (53.6% vs. 7.2% vs. 32.1%; p<0.0001). Efficacy was maintained until week 52. The rate of adverse events with deucravacitinib was comparable to the placebo and apremilast study arms.<\/p>\n\n

** PASI75=at least 75% reduction in Psoriasis Area and Severity Index<\/em>.\u00a3<\/sup> sPGA 0\/1=static Physician’s Global Assessment Score of<\/em> 0 or 1.<\/p>\n\n

<\/p>\n\n

Literature: <\/p>\n\n

    \n
  1. Feldman SR, et al: Relative importance of mode of administration in treatment preferences among plaque psoriasis patients in the United States. JHEOR 2016; 4(2): 141-157. <\/li>\n\n\n\n
  2. Ghoreschi K, et al: TYK2 inhibition: potential in the treatment of chronic inflammatory immune diseases. JDDG 2021; 19(10): 1409-1420.<\/li>\n\n\n\n
  3. Papp K, et al: Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med 2018; 379(14): 1313-1321. <\/li>\n\n\n\n
  4. European Medicines Agency (EMA): Summary ofOpinion, 01\/26\/2013, www.ema.europa.eu\/en\/documents\/smop-initial\/chmp-summary-positive-opinion-sotyktu_en.pdf,<\/a>(last accessed 02\/09\/2023). <\/li>\n\n\n\n
  5. Armstrong AW, 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. JAAD 2023; 88(1): 29-39.<\/li>\n\n\n\n
  6. Rusi\u00f1ol L, Puig L: Tyk2 Targeting in Immune-Mediated Inflammatory Diseases. International Journal of Molecular Sciences 2023; 24(4): 3391.https:\/\/doi.org\/10.3390\/ijms24043391.<\/a><\/li>\n<\/ol>\n\n

    <\/p>\n\n

    DERMATOLOGIE PRAXIS 2023; 33(1): 28<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    Psoriasis is nowadays understood as a systemic disease, which is based on chronic inflammation. Research into the etiopathogenesis, as well as the establishment of new active substances, is progressing rapidly.…<\/p>\n","protected":false},"author":7,"featured_media":351592,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"pmpro_default_level":"","cat_1_feature_home_top":false,"cat_2_editor_pick":false,"csco_eyebrow_text":"Plaque psoriasis ","footnotes":""},"category":[11331,11340,11480,11548,11503],"tags":[23614,56439,66164,66154,35760,12520,14032,66148,66159],"powerkit_post_featured":[],"class_list":["post-352488","post","type-post","status-publish","format-standard","has-post-thumbnail","category-allergology-and-clinical-immunology","category-dermatology-and-venereology","category-rheumatology","category-rx-en","category-studies","tag-active-substances","tag-chronic-inflammation","tag-deucravacitinib-en","tag-etiopathogenesis","tag-oral-en","tag-plaque-psoriasis-en","tag-psoriasis-en-2","tag-systemic-disease-understood","tag-tyk2-inhibition-en","pmpro-has-access"],"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-06-19 17:45:09","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"wpml_current_locale":"en_US","wpml_translations":{"fr_FR":{"locale":"fr_FR","id":352422,"slug":"linhibition-de-tyk2-montre-un-grand-potentiel-therapeutique","post_title":"L'inhibition de TYK2 montre un grand potentiel th\u00e9rapeutique","href":"https:\/\/medizinonline.com\/fr\/linhibition-de-tyk2-montre-un-grand-potentiel-therapeutique\/"},"it_IT":{"locale":"it_IT","id":352452,"slug":"linibizione-di-tyk2-mostra-un-grande-potenziale-terapeutico","post_title":"L'inibizione di TYK2 mostra un grande potenziale terapeutico","href":"https:\/\/medizinonline.com\/it\/linibizione-di-tyk2-mostra-un-grande-potenziale-terapeutico\/"},"pt_PT":{"locale":"pt_PT","id":352485,"slug":"a-inibicao-de-tyk2-mostra-um-grande-potencial-terapeutico","post_title":"A inibi\u00e7\u00e3o de TYK2 mostra um grande potencial terap\u00eautico","href":"https:\/\/medizinonline.com\/pt-pt\/a-inibicao-de-tyk2-mostra-um-grande-potencial-terapeutico\/"},"es_ES":{"locale":"es_ES","id":352497,"slug":"la-inhibicion-de-tyk2-muestra-un-gran-potencial-terapeutico","post_title":"La inhibici\u00f3n de TYK2 muestra un gran potencial terap\u00e9utico","href":"https:\/\/medizinonline.com\/es\/la-inhibicion-de-tyk2-muestra-un-gran-potencial-terapeutico\/"}},"_links":{"self":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/352488","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/comments?post=352488"}],"version-history":[{"count":1,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/352488\/revisions"}],"predecessor-version":[{"id":352499,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/posts\/352488\/revisions\/352499"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media\/351592"}],"wp:attachment":[{"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/media?parent=352488"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/category?post=352488"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/tags?post=352488"},{"taxonomy":"powerkit_post_featured","embeddable":true,"href":"https:\/\/medizinonline.com\/en\/wp-json\/wp\/v2\/powerkit_post_featured?post=352488"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}