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Immune factors such as interferon‑ɣ and interleukin 4 belong to the group of cytokines that are dependent on type I/II receptors for their signal transmission. Upon activation, these receptors transmit their signal to the cell nucleus and, thus, modulate gene transcription via a signaling cascade consisting of Janus kinases (JAK). This family of four kinases (JAK 1, JAK 2, JAK 3, and tyrosine kinase 2 (TYK2)) subsequently activate members of the signal transducer and activator of transcription (STAT). This finding turned the JAK/STAT signaling pathway into a pharmacological target for the treatment of inflammatory diseases in which cytokines using type I/II receptors play a pathogenic role. In 2018, the European Medicines Agency (EMA) approved tofacitinib for the treatment of psoriatic arthritis. This was the first approval of a JAK/STAT pathway inhibitor for patients treated by dermatologists and rheumatologists. Since then, several new JAK inhibitors have been approved for dermatologic diseases such as atopic dermatitis, alopecia areata, vitiligo, and plaque-type psoriasis. In addition, JAK inhibitors are being investigated for the treatment of many other skin diseases. Thus, systemic JAK inhibitors complete the spectrum of immunotherapeutics with a broader immunological approach compared to monoclonal antibodies. The low molecular weight of JAK inhibitors enables the preparation of these drugs for both systemic and topical administration. Their utilization could represent a valuable alternative to topical steroids. The safety profile of JAK inhibitors must be taken into account. Possible long-term effects may become apparent in the next few years. This article describes both approved JAK inhibitors and relevant new JAK inhibitors that are promising candidates for approval as therapeutics in dermatology., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Chronic inflammatory skin diseases are of great social and medical importance and require effective drug therapy. Phosphodiesterase 4 (PDE4) inhibitors represent a possible therapeutic option by regulating inflammatory processes. PDEs cause the release of proinflammatory cytokines by interfering with signaling pathways. The PDE4 inhibitors apremilast (treatment of psoriasis and Behçet's disease), roflumilast (treatment of chronic obstructive pulmonary disease), and crisaborole (treatment of atopic dermatitis) are currently approved in Europe., Psoriasis: Apremilast is used for second-line treatment of plaque psoriasis and psoriatic arthritis and has a favorable side effect profile. Topical PDE4 inhibitors are currently being researched and have not yet been approved by the European Medicines Agency (EMA)., Atopic Dermatitis: The topical PDE4 inhibitor crisaborole was approved by the EMA in 2020 as a topical treatment alternative to glucocorticoids and calcineurin inhibitors. Although the substance has shown good tolerability in studies and also alleviates the accompanying itching, it did not find its way onto the German market. BEHçET'S DISEASE: Apremilast is approved for the treatment of Behçet's disease in adults with refractory, severe oral ulcers., Outlook: Case studies have also demonstrated the efficacy of systemic PDE4 inhibition in other skin diseases (including blistering autoimmune dermatoses, lichen planus, and acantholytic genodermatoses). The substances are also being researched and used to treat extracutaneous inflammatory diseases., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The importance of topically applied pharmaceuticals, especially for the treatment of dermatological diseases, is still essential. Thanks to detailed knowledge of the organisation and function of the physicochemical barrier of the skin, new galenic concepts have increasingly been developed to market maturity in recent years. Colloidal drug carrier systems in particular, but also targeted physicochemical modifications of matrices are used to optimise the cutaneous bioavailability of topically applied drugs. In addition, new molecules are increasingly becoming available for the development of these preparations or drugs known from systemic therapy are being formulated into topicals. Against this background, dermatopharmacology is also developing more and more into a highly specialised science in this area, which is producing innovative concepts for the therapy of special indications. In addition to the classic small-molecule drugs, biotechnological molecules are increasingly finding their way into application, so that a modern age of dermatopharmacology has dawned, which will open up previously unimagined possibilities for topical therapy now and in the coming years., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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]

For the treatment of moderate to severe atopic dermatitis (AD), two groups of modern systemic therapies with a total of five drugs are currently approved in Germany: biologics (dupilumab, tralokinumab) and "small molecules" (abrocitinib, baricitinib, upadacitinib). The growing armamentarium of therapy options, especially with more than one drug per substance group, makes it challenging for practitioners to select the appropriate treatment for the individual patient. In this review article, the preconditions and requirements of each drug group as well as the corresponding substances are presented comparatively. On the one hand, direct therapeutic effects on the severity of the disease are considered and, on the other hand, the spectrum of potential adverse drug reactions are discussed. In particular, short- and long-term effects, the safety profile and the patient's concomitant diseases represent key factors for shared decision-making with regard to select the optimum personalized therapy option., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

In 1997 rituximab, a genetically engineered chimeric monoclonal antibody (mAb) targeting CD20 expressed on B cells was approved for treatment of non-Hodgkin's lymphoma. Since then, pharmacological improvements combined with increased knowledge on the immunopathogenesis of diseases led to the development of specific mAb targeting different antigens (e.g., interleukins or transmembrane receptors). This approach reshaped the therapeutic methodology in many fields, including dermatology. Nowadays, the treatment of frequent and possibly impairing inflammatory disorders such as psoriasis, atopic dermatitis or hidradenitis suppurativa have different mAbs approved for both adult and pediatric patients. This class of drugs often shows a more favorable outcome and a better safety profile than routine immunosuppressants, such as steroids and steroid-sparing substances. For many years mAbs also represented a pillar of oncological treatment for severe diseases such as malignant melanoma or Merkel cell carcinoma. This review summarizes the current knowledge on already approved and promising new mAbs for the treatment of inflammatory and oncological skin diseases., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Copyright of Spektrum der Augenheilkunde 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.)

Psoriasis is a chronic inflammatory systemic disease that requires optimal long-term management due to its high prevalence in the population and the numerous comorbidities that severely impair quality of life. A variety of treatment options are now available. In addition to objective skin findings and a specific location such as nails or genital area, the presence of psoriatic arthritis and other comorbidities as well as the disease burden of the affected person play a decisive role in individualized treatment decision-making. Good communication with the patient is fundamental to understand the individual needs and expectations of the patient. Shared decision-making can positively influence adherence and thus also the clinical outcome and patient satisfaction. In addition, interdisciplinary collaboration is crucial and often necessary for a comprehensive therapy strategy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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]

Copyright of Zeitschrift für Rheumatologie 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.)

Janus kinase inhibitors (JAKi) represent an immunomodulatory targeted therapy in various dermatoses. Throughout the past few years, JAKi have been approved for atopic dermatitis (AD), psoriasis vulgaris (PSO), alopecia areata (AA), and vitiligo. Further indications are currently under investigation. In this article the various systenic and topical JAKi used in dermatology are being presented regarding their efficacy and safety profile. A specific focus will be set on handling with safety issues including screening and control measures during treatment with JAKi. In addition, future use of JAKi in various dermatological diseases for which nowadays only insufficient therapy options are available is being discussed., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief., Objective: Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given., Material and Methods: Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented., Results: In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T‑helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC)., Conclusion: A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Due to its high prevalence and associated socioeconomic consequences, hand eczema is a burden for those affected and for society. The various hand eczema subtypes must be differentiated from each other through structured anamnesis and diagnostics in order to initiate cause-related preventive measures in addition to symptomatic therapy. There are new developments in the diagnosis, prevention, and treatment of hand eczema. The diagnostic possibilities are being expanded through molecular methods. Modern topical and systemic therapies offer promising treatment options for patients with atopic but also chronic hand eczema regardless of the underlying etiology., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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]

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]