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Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far.

ABSTRACT: Psoriatic arthritis (PsA) is a heterogeneous disease that may develop in up to 30% of patients with psoriasis. PsA mainly involves peripheral joints; however, axial skeleton and entheses can also be involved. PsA is the result of a complex interplay between an individual's genotype and environmental factors that triggers an immune response and leads to the production of a cytokine cascade. Even though there are about 17 targeted therapies for PsA, a significant percentage of patients fail to respond to such treatments, have a partial response or develop side-effects. This article aims to review the current knowledge on deucravacitinib, a new oral small molecule that selectively inhibits tyrosine kinase 2 (TYK2), for the treatment of PsA. TYK2, a member of the Janus kinase (JAK) family, is responsible for mediating intracellular signalling of cytokines involved in the pathogenesis of PsA and psoriasis, namely IL-12, IL-23, and type I interferons. Recently, deucravacitinib was approved by the FDA for the treatment of moderate-to-severe plaque psoriasis and is currently being evaluated in phase III clinical trials in PsA. In a phase II clinical trial, deucravacitinib showed sustained effectiveness in several domains of PsA, namely arthritis, enthesitis and dactylitis, was well tolerated, and had a favourable safety profile. In patients with psoriasis, deucravacitinib had shown a higher efficacy than placebo and apremilast. Deucravacitinib is a promising therapy, with a unique mechanism of action. Results from the phase III programme and studies evaluating long-term response and head-to-head comparisons with other targeted agents will be important to establishing the position of deucravacitinib in the management of PsA.

SUBMITTER: Martins A

PROVIDER: S-EPMC10166261 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far.

Martins Ana A Lé Ana Maria AM Torres Tiago T

Drugs in context 20230503

Psoriatic arthritis (PsA) is a heterogeneous disease that may develop in up to 30% of patients with psoriasis. PsA mainly involves peripheral joints; however, axial skeleton and entheses can also be involved. PsA is the result of a complex interplay between an individual's genotype and environmental factors that triggers an immune response and leads to the production of a cytokine cascade. Even though there are about 17 targeted therapies for PsA, a significant percentage of patients fail to res ...[more]

PMID: 37168876

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Project description:IntroductionRheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (PSO) are chronic inflammatory diseases that have a substantial impact on patients' health. This retrospective database study aimed to assess the epidemiology, comorbidities, diagnosis and treatment patterns of RA, PsA and PSO in the German population.MethodsData were extracted from the Deutsche Forschungsdatenbank für Abrechnungsinformationen der Krankenversicherung database from 2012 to 2016 for patients aged ≥ 18 years holding full health coverage in the reporting year at least. Diagnoses were defined according to International Classification of Diseases (ICD)-10 codes. Reported outcomes included prevalence and incidence rates, pre-defined comorbidities, diagnosing and treating physicians, and treatment exposure. A subgroup analysis was performed for women of childbearing age (females aged 18-45 years).ResultsThe prevalence rates of RA, PsA and PSO in Germany were consistent over the study period; by 2016 they were 0.4%, 0.3% and 2.1%, respectively, and in women of childbearing age they were 0.2%, 0.2% and 1.5%, respectively. RA, PsA and PSO were predominantly observed among patients aged > 45 years. RA and PsA were more prevalent in women, while PSO had an approximately equal gender distribution. Depressive episodes were the most frequently reported comorbidity in 2016 (RA: 25.7%; PsA: 25.1%; PSO: 17.8%), and this was similar in women of childbearing age (RA: 20.5%; PsA: 23.4%; PSO: 16.3%). Approximately 50% of patients with RA and PsA and 6% of patients with PSO were receiving systemic treatment in 2016, of which methotrexate (RA: 38.4%; PsA: 30.2%; PSO: 2.2%) was most common. Biologic therapies were the least frequently used treatment options (RA: 28.9%; PsA: 20.9%; PSO: 1.8%).ConclusionsThis analysis provides key epidemiological information for patients with RA, PsA and PSO, including in women of childbearing age, in Germany and highlights common comorbidities and that patients were likely receiving insufficient treatment for these diagnoses.

Project description:IntroductionPsoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required.ObjectivesThe interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides. Herein, we review data from clinical studies with secukinumab, a novel fully human IgG1κ anti-IL-17A monoclonal antibody (mAb), in patients with active PsA.ResultsAcross two pivotal phase 3 studies, secukinumab provided significant and sustained reductions in the signs and symptoms of PsA, inhibition of radiographic progression, and improved patient-reported outcomes and measures of quality of life. The primary efficacy endpoint, a ≥20% improvement from baseline according to the American College of Rheumatology 20 (ACR20) response at Week 24, was significantly higher in patients treated with secukinumab compared with placebo, with improvements sustained through at least 52 weeks. Clinical benefits were seen with secukinumab regardless of concomitant methotrexate treatment and in patients who were either anti-TNF-naïve or who were inadequate responders to anti-TNF therapy. Secukinumab was well-tolerated, with a safety profile consistent with that previously reported in psoriasis trials. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and headache.ConclusionSecukinumab offers an effective new addition to the available treatment options for PsA. Regulatory submissions have been filed worldwide, with the first approvals recently obtained in Japan and Europe. Future studies are required to define the optimal timing and strategic use of this novel treatment modality.FundingNovartis Pharma.

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Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far.

Publications

Deucravacitinib for the treatment of psoriatic arthritis: the evidence so far.

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