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J Clin Aesthet Dermatol. 2024 May;17(5 Suppl 2):S7-S10. NO ABSTRACT PMID:38726208 | PMC:PMC11078528 Den ganzen Artikel lesen

Ital J Dermatol Venerol. 2024 May 10. doi: 10.23736/S2784-8671.24.07664-3. Online ahead of print. ABSTRACT SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients. PMID:38727633 | DOI:10.23736/S2784-8671.24.07664-3 Den ganzen Artikel lesen

Ital J Dermatol Venerol. 2024 May 10. doi: 10.23736/S2784-8671.24.07666-7. Online ahead of print. ABSTRACT SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology. PMID:38727634 | DOI:10.23736/S2784-8671.24.07666-7 Den ganzen Artikel lesen

Mol Biol Rep. 2024 May 10;51(1):635. doi: 10.1007/s11033-024-09337-4. ABSTRACT BACKGROUND: Psoriasis, a chronic inflammatory skin disease, is increasingly effectively managed with the targeted immunotherapy; however, long-term immunotherapy carries health risks, and loss of response. Therefore, we need to develop the alternative treatment strategies. Mesenchymal stem/stromal cell (M.S.C.) exosomes stand out for their remarkable immunomodulatory properties, gaining widespread recognition. This study investigated whether M.S.C. exosomes can reduce psoriasis-induced hyperplasia by inducing Transforming Growth Factor beta 2 (TGF-beta2) signaling. METHODOLOGY: Exosomes were isolated from M.S.C.s by ultracentrifugation. Then, scanning electron microscopy was used for the morphology of exosomes. To ascertain the exosome concentration, the Bradford test was used. To ascertain the cellular toxicity of exosomes in Human Umbilical Vein Endothelial Cells ( H.U.V.E.C), an MTT experiment was then conducted. Real-time PCR was used to quantify TGF beta2 expression levels, whereas an ELISA immunosorbent assay was used to determine the protein concentration of TGF beta2. RESULTS: In this study, the exosomes of 15-30 nm in size that were uniform, and cup-shaped were isolated. Moreover, the IC50 value for this Treatment was calculated to be 181.750 µg/ml. The concentration of TGF-β2 gene in the target cells significantly increased following Treatment with the exosomes. Furthermore, the expression level of the studied gene significantly increased due to the Treatment. CONCLUSION: Upregulating the expression of TGF-β2 in psoriatic cells via TGF-β2 signaling is one way exosomes can help reduce hyperplasia. PMID:38727850 | DOI:10.1007/s11033-024-09337-4 Den ganzen Artikel lesen

Dermatol Ther (Heidelb). 2024 May 10. doi: 10.1007/s13555-024-01170-8. Online ahead of print. ABSTRACT INTRODUCTION: There are several treatment options for plaque psoriasis (PsO), but uncertainty remains around the optimal sequencing of treatments. The aims of this study were to investigate how adopting a best-treatment-first treatment sequence impacts patient outcomes and healthcare systems and to quantify the cost of treatment failure to the healthcare system. METHODS: A 3-year state-transition treatment-sequencing model which identifies all possible treatment sequences in PsO was adapted to the Italian healthcare setting. Treatments considered in the model are those with European Medicines Agency marketing authorization and reimbursement in Italy as of December 2022. Italian market share data (2019-2021) and list prices (2022) informed the current prescribed sequences; these sequences were compared against all possible sequences to determine opportunities for improvement. Both the national perspective in Italy as well as the local perspective from seven regions were considered. The cost of treatment failure was informed through a questionnaire circulated to Italian dermatologists. RESULTS: Overall, 1284 possible treatment sequences are possible when four lines of treatment are considered for patients with moderate-to-severe PsO in Italy. Within the estimated range of treatment failures across those sequences (0.97-2.56 per patient over 3 years), current prescribing behavior from the national perspective suggests patients will face 1.44 failures on average; this highlights the potential for improvement. For every treatment failure, the cost borne by the Italian National Healthcare Service (NHS) is €676.80. Overall, prescribing more optimized treatment sequences results in a 22.95% reduction in failures with a 2.27% increase in costs. The regional analyses found similar trends. CONCLUSIONS: Results suggest that selecting the most effective treatment sequences for incident patients provides the greatest opportunity to reduce treatment failures and maximize patient outcomes with a modest impact on costs. While regional variations exist, there is room for improvement across the board, which could translate to more efficient local healthcare systems. PMID:38727995 | DOI:10.1007/s13555-024-01170-8 Den ganzen Artikel lesen

Dermatol Ther (Heidelb). 2024 May 10. doi: 10.1007/s13555-024-01164-6. Online ahead of print. ABSTRACT INTRODUCTION: Real-world data on the efficacy of risankizumab (RZB) in clinical moderate-to-severe plaque psoriasis (PsO) are limited. The RAPID study assessed real-world clinical and patient-reported outcomes in RZB-treated PsO patients using data collected from dermatologists in Canada, the Czech Republic, Germany, Japan, and Poland. METHODS: This ongoing, retrospective chart review collected data from medical records of RZB-treated adults with moderate-to-severe PsO (09/2022-06/2023). Eligible patients received RZB, had ≥ 12 months of medical records after RZB initiation (index date), and had Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA), or static Physician's Global Assessment (sPGA) scores ≥ 3 months before and up to 18 months after the index date. The proportion of patients achieving a clear/almost clear PsO (IGA/sPGA = 0/1), PASI ≤ 1, Dermatology Life Quality Index (DLQI) = 0/1, and a 90%/100% improvement from baseline in PASI as well as the mean changes in PASI, DLQI, itch, and skin pain scores at 12 and 18 months were reported for patients with non-missing assessments at baseline and 12 months. RESULTS: Most patients (66.4%) were male, 74.0% were biologic naïve, and 73.0% had scalp PsO. Mean baseline IGA/sPGA was 3.7 ± 0.5, with a mean PASI of 23.3 ± 11.8. After 12 months, 86.1% of patients reported IGA/sPGA ≤ 1, and 75.7% achieved PASI90; these further increased to 91.1% and 80.5% at 18 months. DLQI, itch, and skin pain scores improved over time. CONCLUSIONS: These data demonstrated the durable, real-world effectiveness of RZB in patients with moderate-to-severe PsO through continued improvement in disease and symptom severity over 18 months, with most of the patients reporting clear/almost clear skin. PMID:38727996 | DOI:10.1007/s13555-024-01164-6 Den ganzen Artikel lesen

PLoS One. 2024 May 10;19(5):e0303058. doi: 10.1371/journal.pone.0303058. eCollection 2024. ABSTRACT BACKGROUND: Shared decision-making (SDM) refers to a collaborative process in which clinicians assist patients in making medically informed, evidence-based decisions that align with their values and preferences. There is a paucity of literature on SDM in dermatology. OBJECTIVE: We aim to assess whether male and female psoriasis patients evaluate their clinicians' engagement in SDM differently across different age groups. METHODS: Cross-sectional study using data from the 2014-2017 and 2019 Medical Expenditure Panel Surveys (MEPS). RESULTS: A weighted total of 7,795,608 psoriasis patients were identified. SDM Scores ranged from 1 to 4, with 4 representing the most favorable patient evaluation of their clinicians' engagement in SDM. We conducted multivariate linear regression to compare mean SDM Scores in male psoriasis patients versus female psoriasis patients across different patient age groups. Female patients ages 60-69 perceived significantly greater clinician engagement in SDM compared to age-matched male patients (female patient perception of SDM 3.65 [95%CI:3.61-3.69] vs. male patient perception of SDM 3.50 [95%CI:3.43-3.58], p<0.005). The same trend of older female patients evaluating their clinicians' engagement in SDM significantly higher than their age-matched male counterparts exists for the age group >70 (p<0.005). No significant differences between male and female patients' evaluations of their clinicians' engagement in SDM were demonstrated in subjects younger than 60. All calculations were adjusted for demographic and clinical factors. CONCLUSIONS: Compared to older male psoriasis patients, older female psoriasis patients evaluated their clinicians to be more engaged in shared decision-making. PMID:38728289 | DOI:10.1371/journal.pone.0303058 Den ganzen Artikel lesen

Medicine (Baltimore). 2024 May 10;103(19):e38055. doi: 10.1097/MD.0000000000038055. ABSTRACT Multiple studies have indicated a potential correlation between immune-mediated inflammatory diseases (IMIDs) and Frozen shoulder (FS). To explore the genetic causal relationship between IMIDs and FS using 2-sample Mendelian randomization (MR) analysis. Genome-wide association study (GWAS) summary data for FS were obtained from Green's study, while data for 10 IMIDs were sourced from the FinnGen Consortium. The MR analysis was performed using inverse variance weighting, MR Egger, and weighted median methods. IVW, as the primary MR analysis technique, was complemented with other sensitivity analyses to validate the robustness of the results. Additionally, reverse MR analysis was further conducted to investigate the presence of reverse causal relationships. In the forward MR analysis, genetically determined 4 IMIDs are causally associated with FS: rheumatoid arthritis (odds ratio [OR] (95% confidence interval [95% CI]) = 1.05 [1.02-1.09], P < .01); type 1 diabetes (OR [95% CI] = 1.06 [1.03-1.09], P < .01); hypothyroidism (OR [95% CI] = 1.07 [1.01-1.14], P = .02); and Celiac disease (OR [95% CI] = 1.02 [1.01-1.04], P = .01). However, no causal relationship was found between 6 IMIDs (autoimmune hyperthyroidism, Crohn disease, ulcerative colitis, psoriasis, sicca syndrome and systemic lupus erythematosus) and FS. Sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy. In the reverse MR analysis, no causal relationship was observed between FS and IMIDs. In conclusion, this MR study suggests a potential causal relationship between rheumatoid arthritis, type 1 diabetes, hypothyroidism, and Celiac disease in the onset and development of FS. Nevertheless, more basic and clinical research will be needed in the future to support our findings. PMID:38728465 | DOI:10.1097/MD.0000000000038055 Den ganzen Artikel lesen

Nat Commun. 2024 May 9;15(1):3901. doi: 10.1038/s41467-024-48288-z. ABSTRACT Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB. PMID:38724505 | DOI:10.1038/s41467-024-48288-z Den ganzen Artikel lesen

Dermatol Ther (Heidelb). 2024 May 9. doi: 10.1007/s13555-024-01162-8. Online ahead of print. ABSTRACT INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals. PMID:38724839 | DOI:10.1007/s13555-024-01162-8 Den ganzen Artikel lesen

Journal of the European Academy of Dermatology and Venereology Volume 38, Issue 5 p. 784-785 Open Access Florence Dalgard, Corresponding Author Florence …Den ganzen Artikel lesen

Türel Ermertcan A, Temeltaş G, Deveci A, Dinç G, Güler HB, Oztürkcan S. Türel Ermertcan A, et al. J Dermatol. 2006 Nov;33(11):772-8. doi: …Den ganzen Artikel lesen

1. Diotallevi F., Paolinelli M., Radi G., Offidani A. Latest combination therapies in psoriasis: narrative review of the literature. Dermatol Ther. …Den ganzen Artikel lesen

Jeeyu Choi, Jeeyu Choi School of Dentistry, Pusan National University, Yangsan, Republic of Korea Search for more papers by this author Ikjoon Han, Ikjoon …Den ganzen Artikel lesen

Harmer B, Lee S, Duong TVH, Saadabadi A. Harmer B, et al. 2024 Feb 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 …Den ganzen Artikel lesen

Mao KL, Fan ZL, Yuan JD, Chen PP, Yang JJ, Xu J, ZhuGe DL, Jin BH, Zhu QY, Shen BX, Sohawon Y, Zhao YZ, Xu HL. Mao KL, et al. Colloids Surf B …Den ganzen Artikel lesen

Full text linksCite Display options Display options The aim of this review is to provide a summary of the botany, phytochemistry and dermatological …Den ganzen Artikel lesen

Harmer B, Lee S, Duong TVH, Saadabadi A. Harmer B, et al. 2024 Feb 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 …Den ganzen Artikel lesen

Full text linksCite Display options Display options Background: Selenium sulfide, available as a shampoo or topical lotion at 1%, or 2.5% concentrations …Den ganzen Artikel lesen

Mital R, Gray A, Minta A, Almhana F, Amin S, Hydol-Smith J, Mallela T, Kaffenberger BH. Mital R, et al. Dermatol Ther (Heidelb). 2023 …Den ganzen Artikel lesen

Rheumatol Adv Pract. 2024 Apr 10;8(2):rkae052. doi: 10.1093/rap/rkae052. eCollection 2024. NO ABSTRACT PMID:38698954 | PMC:PMC11065474 | DOI:10.1093/rap/rkae052 Den ganzen Artikel lesen

Front Genet. 2024 Apr 18;15:1365273. doi: 10.3389/fgene.2024.1365273. eCollection 2024. ABSTRACT BACKGROUND: Psoriasis represents a multifaceted and debilitating immune-mediated systemic ailment afflicting millions globally. Despite the continuous discovery of biomarkers associated with psoriasis, identifying lysosomal biomarkers, pivotal as cellular metabolic hubs, remains elusive. METHODS: We employed a combination of differential expression analysis and weighted gene co-expression network analysis (WGCNA) to initially identify lysosomal genes. Subsequently, to mitigate overfitting and eliminate collinear genes, we applied 12 machine learning algorithms to screen robust lysosomal genes. These genes underwent further refinement through random forest (RF) and Lasso algorithms to ascertain the final hub lysosomal genes. To assess their predictive efficacy, we conducted receiver operating characteristic (ROC) analysis and verified the expression of diagnostic biomarkers at both bulk and single-cell levels. Furthermore, we utilized single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, and Pearson's correlation analysis to elucidate the association between immune phenotypes and hub lysosomal genes in psoriatic samples. Finally, employing the Cellchat algorithm, we explored potential mechanisms underlying the participation of these hub lysosomal genes in cell-cell communication. RESULTS: Functional enrichment analyses revealed a close association between psoriasis and lysosomal functions. Subsequent intersection analysis identified 19 key lysosomal genes, derived from DEGs, phenotypic genes of WGCNA, and lysosomal gene sets. Following the exclusion of collinear genes, we identified 11 robust genes, further refined through RF and Lasso, yielding 3 hub lysosomal genes (S100A7, SERPINB13, and PLBD1) closely linked to disease occurrence, with high predictive capability for disease diagnosis. Concurrently, we validated their relative expression in separate bulk datasets and single-cell datasets. A nomogram based on these hub genes may offer clinical advantages for patients. Notably, these three hub genes facilitated patient classification into two subtypes, namely metabolic-immune subtype 1 and signaling subtype 2. CMap analysis suggested butein and arachidonic fasudil as preferred treatment agents for subtype 1 and subtype 2, respectively. Finally, through Cellchat and correlation analysis, we identified PRSS3-F2R as potentially promoting the expression of hub genes in the psoriasis group, thereby enhancing keratinocyte-fibroblast interaction, ultimately driving psoriasis occurrence and progression. CONCLUSION: Our study identifies S100A7, SERPINB13, and PLBD1 as potential diagnostic biomarkers, offering promising prospects for more precisely tailored psoriatic immunotherapy designs. PMID:38699235 | PMC:PMC11063342 | DOI:10.3389/fgene.2024.1365273 Den ganzen Artikel lesen

J Clin Periodontol. 2024 May 3. doi: 10.1111/jcpe.13996. Online ahead of print. ABSTRACT AIM: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models. MATERIALS AND METHODS: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm2]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-α) were collected. RESULTS: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm2) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05). CONCLUSIONS: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation. PMID:38699834 | DOI:10.1111/jcpe.13996 Den ganzen Artikel lesen

Expert Opin Drug Saf. 2024 May 3. doi: 10.1080/14740338.2024.2351462. Online ahead of print. ABSTRACT INTRODUCTION: Nowadays, despite the wide availability of biological drugs and apremilast for psoriasis management, there is always a need for new therapies to customize the therapeutic approach on the basis of the patient's clinical features and comorbidities, especially in order to achieve a prolonged therapeutic response. Thus, new treatment strategies are required to offer patients a personalized approach. In this scenario, major knowledge on psoriasis pathogenesis led to the development of deucravacitinib, an orally administered selective TYK2 inhibitor. AREAS COVERED: The aim of this manuscript is to review current literature on the effectiveness and safety of deucravacitinib in psoriasis to offer readers a wide perspective. The current English literature was analyzed using the PubMed, Google Scholar, Embase, Cochrane Skin, and clinicaltrials.gov databases, selecting the most relevant manuscripts. EXPERT OPINION: Deucravacitinib appears to be an innovative weapon for the management of moderate to severe psoriasis. Despite its efficacy and safety profiles have been revealed by RCTs, real-life data are still scant. Certainly, deucravacitinib broadens the range of therapeutic alternatives for psoriasis patients, thus enhancing the holistic and personalized approach required for the treatment of this disease. PMID:38699874 | DOI:10.1080/14740338.2024.2351462 Den ganzen Artikel lesen

Clin Exp Dermatol. 2024 May 3:llae152. doi: 10.1093/ced/llae152. Online ahead of print. ABSTRACT BACKGROUND: Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. OBJECTIVE: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. METHODS: In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. RESULTS: Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. CONCLUSIONS: Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued. PMID:38699939 | DOI:10.1093/ced/llae152 Den ganzen Artikel lesen