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Background: Two phase 3 trials, POETYK PSO-1 and PSO-2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis. Objectives: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. Methods: Pooled safety data were evaluated from PSO-1 and PSO-2 in which patients with moderate-to-severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast. Results: A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure-adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person-years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Die atopische Dermatitis (AD) ist die häufigste entzündliche Haut-erkrankung und gilt als komplexe und heterogene Erkrankung. Kürzlich wurden verschiedene AD-Phänotypen beschrieben, die nach dem Alter des Patienten zu Beginn, dem ethnischen Hintergrund, der Krankheitsdauer und anderen Krankheitsmerkmalen definiert wurden und der Notwendigkeit eines personalisierten Behandlungsansatzes zugrunde liegen. Jüngste Fortschritte beim Verständnis der AD-Pathogenese führten zu einer echten translationalen Revolution und zu einer exponentiellen Erweiterung der therapeutischen Pipeline. Die Untersuchung von Biomarkern in klinischen Studien zu neuen Behandlungen trägt dazu bei, die Rolle jedes Zytokins und Immunwegs bei der AD zu klären und wird es ermöglichen, den einzigartigen immunologischen Fingerabdruck jeder AD-Untergruppe zu adressieren. Die personalisierte Medizin wird das ultimative Ziel dieser gezielten translationalen Forschung sein. In dieser Übersichtsarbeit diskutieren wir die Veränderungen in den Konzepten sowohl der Pathogenese als auch des Behandlungsansatzes für AD, heben die wissenschaftliche Begründung für jede zielgerichtete Behandlung hervor und berichten über die neuesten klinischen Daten zur Wirksamkeit. [ABSTRACT FROM AUTHOR]

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Hintergrund: Psoriasis ist eine immunvermittelte, langwierige Erkrankung, von der weltweit etwa 100 Millionen Menschen betroffen sind. Anti-Interleukin (IL)-23-Wirkstoffe haben einen besonderen Status in Bezug auf die Sicherheit und klinische Wirksamkeit. Anti-IL-23-Wirkstoffe haben in früheren weltweiten Forschungsarbeiten therapeutische Vorteile bei Psoriasis gezeigt. Allerdings war bei der Behandlung von Psoriasis eine Reihe von Nebenwirkungen mit den Anti-IL-23-Wirkstoffen assoziiert. Ziel dieser systematischen Übersichtsarbeit war es, die in Phase-III-Studien ermittelten Nebenwirkungen von Anti-IL-23-Wirkstoffen bei Patienten mit Psoriasis zu bewerten. Methodik: Für diese systematische Übersichtsarbeit wurden die PRISMA-Richtlinien herangezogen. Die Autorin durchsuchte systematisch die Datenbanken Google Scholar, PubMed, Scopus und Cochrane, um geeignete Artikel über Nebenwirkungen von Anti-IL-23-Wirkstoffen bei Patienten mit Psoriasis zu finden, einschließlich der entsprechenden Schlüsselbegriffe (Medical Subject Headings). Ergebnisse: Insgesamt 18 Studien, die die Auswahlkriterien erfüllten, wurden in diesen hochaktuellen systematischen Übersichtsartikel einbezogen. In diesem Review war die häufigste Nebenwirkung von Anti-IL-23-Wirkstoffen Nasopharyngitis, gefolgt von Kopfschmerzen, Infektionen der oberen Atemwege und Rückenschmerzen, die während der Behandlung mit Anti-IL-23-Wirkstoffen beobachtet werden. Die Anti-IL-23-Mittel Ustekinumab und Guselkumab waren signifikant an den Stufe-3-Nebenwirkungen bei der Behandlung von Psoriasis beteiligt, während die Anti-IL-23-Wirkstoffe Briakinumab, Tildrakizumab und Risankizumab signifikant an den Stufe-4-Nebenwirkungen beteiligt waren. Schlussfolgerung: Die zielgerichtete IL-23-Therapie hat einen raschen Aufschwung erlebt, da die Bedeutung der IL-23-Achse zunehmend erkannt wurde und einen neuen Maßstab für Behandlungsergebnisse bei Psoriasis gesetzt hat. In den letzten 3 Jahren sind nacheinander Ustekinumab, Guselkumab, Tildrakizumab und Risankizumab auf den Markt gekommen. Diese Medikamente verursachten jedoch mehrere immunologische und nicht immunologische Nebenwirkungen, sind aber in der Regel gut verträglich und haben ordnungsgemäße Sicherheitsvignetten. [ABSTRACT FROM AUTHOR]

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Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Effective, well-tolerated oral psoriasis treatments are needed. Objective: To compare the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, versus placebo and apremilast in adults with moderate to severe plaque psoriasis. Methods: Participants were randomized 2:1:1 to deucravacitinib 6 mg every day (n = 332), placebo (n = 166), or apremilast 30 mg twice a day (n = 168) in the 52-week, double-blinded, phase 3 POETYK PSO-1 trial (NCT03624127). Coprimary end points included response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) with deucravacitinib versus placebo at week 16. Results: At week 16, response rates were significantly higher with deucravacitinib versus placebo or apremilast for PASI 75 (194 [58.4%] vs 21 [12.7%] vs 59 [35.1%]; P <.0001) and sPGA 0/1 (178 [53.6%] vs 12 [7.2%] vs 54 [32.1%]; P <.0001). Efficacy improved beyond week 16 and was maintained through week 52. Adverse event rates with deucravacitinib were similar to those with placebo and apremilast. Limitations: One-year duration, limited racial diversity. Conclusion: Deucravacitinib was superior to placebo and apremilast across multiple efficacy end points and was well tolerated in moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

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Background: Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin. Methods: We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score. Results: In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (p < 0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus. Conclusions: Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.). [ABSTRACT FROM AUTHOR]

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Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)