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      The efficacy and safety of tyrosine kinase 2 inhibitor deucravacitinib in the treatment of plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials

      systematic-review

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          Abstract

          Background

          Orally effective therapeutics for plaque psoriasis with improved response rates, lower toxicity and costs are needed in clinical practices. This study aims to assess the efficacy and safety of the recently approved TYK2 inhibitor deucravacitinib in adults with moderate to severe plaque psoriasis through meta-analysis.

          Methods

          A systematic search was performed for eligible studies using electronic databases, including PubMed, Embase, Cochrane Library, Clinical Trials, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform (ICTRP). Randomized controlled trials (RCTs) comparing the efficacy and safety of deucravacitinib vs. placebo or active comparators in adult patients with plaque psoriasis were included. The effectiveness of deucravacitinib was evaluated using a 75% improvement in Psoriasis Area and Severity Index (PASI 75) from baseline and the proportion of patients achieving the static Physician’s Global Assessment (sPGA) response. The secondary endpoint was the proportion of patients achieving PASI 90, PASI 100, ssPGA 0/1, and Dermatology Life Quality Index 0/1 (DLQI). The incidence of adverse events (AEs), serious AEs (SAEs), and AE-related treatment discontinuation were statistically analyzed to determine the safety of deucravacitinib.

          Results

          The systematic review and meta-analysis included five RCTs involving 2,198 patients with moderate to severe plaque psoriasis. Results showed that deucravacitinib was superior to placebo as well as active comparator apremilast in multiple key endpoints, including PASI 75, sPGA 0/1, PASI 90, PASI 100, DLQI 0/1 at week 16. Moreover, a durable response was seen in the two 52-week studies. Safety assessment showed that deucravacitinib was generally well tolerated, and the incidence of AEs, SAEs, and AE-related treatment discontinuation was low and balanced across groups.

          Conclusion

          Deucravacitinib demonstrated superior efficacy to apremilast in adult patients with moderate to severe plaque psoriasis with an acceptable safety profile and has the potential to be used as the first-line oral therapy for plaque psoriasis.

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          Most cited references33

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study

            Abstract Objective To systematically review and provide information on the incidence of psoriasis and quantify global, regional, and country specific estimates of its prevalence. Design Systematic review and meta-analysis. Data sources Medline, Embase, Web of Science, SciELO, Korean Journal Databases, Russian Science Citation Index, WPRIM, SaudiMedLit, Informit, IndMed, and HERDIN were searched systematically from their inception dates to October 2019. Methods Studies were included if they reported on the incidence or prevalence of psoriasis in the general population. Incidence data were summarised descriptively, whereas bayesian hierarchical models were fitted to estimate the global, regional, and country specific prevalence of psoriasis. Results 41 164 records were identified and 168 studies met the inclusion criteria. In adults, the incidence of psoriasis varied from 30.3 per 100 000 person years (95% confidence interval 26.6 to 34.1) in Taiwan to 321.0 per 100 000 person years in Italy. The prevalence of psoriasis varied from 0.14% (95% uncertainty interval 0.05% to 0.40%) in east Asia to 1.99% (0.64% to 6.60%) in Australasia. The prevalence of psoriasis was also high in western Europe (1.92%, 1.07% to 3.46%), central Europe (1.83%, 0.62% to 5.32%), North America (1.50%, 0.63% to 3.60%), and high income southern Latin America (1.10%, 0.36% to 2.96%). Conclusions Eighty one per cent of the countries of the world lack information on the epidemiology of psoriasis. The disease occurs more frequently in adults than in children. Psoriasis is unequally distributed across geographical regions; it is more frequent in high income countries and in regions with older populations. The estimates provided can help guide countries and the international community when making public health decisions on the appropriate management of psoriasis and assessing its natural history over time. Systematic review registration PROSPERO CRD42019160817.
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              Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis

              Tyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2194389/overviewRole: Role: Role:
                Role:
                Role: Role:
                URI : https://loop.frontiersin.org/people/447080/overviewRole: Role: Role: Role:
                Role: Role: Role: Role:
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                29 September 2023
                2023
                : 10
                : 1264667
                Affiliations
                [1] 1Pharmaceutical Department, PLA Strategic Support Force Medical Center , Beijing, China
                [2] 2Shandong Provincial Center for ADR Monitoring , Jinan, China
                [3] 3Department of Pharmacy, The First Affiliated Hospital of Chengdu Medical College , Chengdu, China
                [4] 4Clinical Medical College, Chengdu Medical College , Chengdu, China
                Author notes

                Edited by: Angelo Ruggiero, University of Naples Federico II, Italy

                Reviewed by: Rosita Comune, University of Campania Luigi Vanvitelli, Italy; Luca Potestio, University of Naples Federico II, Italy

                *Correspondence: Fei Lin, loganfeilin@ 123456hotmail.com
                Article
                10.3389/fmed.2023.1264667
                10570425
                37841017
                b30ab007-64bf-41ed-b4d0-52c0355afcd4
                Copyright © 2023 Qiu, Liu, Liu, Lin and Shi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 August 2023
                : 15 September 2023
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 33, Pages: 11, Words: 5203
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The financial support was received from PLA Strategic Support Force Medical Center for the publication of this article.
                Categories
                Medicine
                Systematic Review
                Custom metadata
                Dermatology

                tyk2 inhibitor,deucravacitinib,psoriasis,autoimmune disease,meta-analysis

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