Applying precision medicine to unmet clinical needs in psoriatic disease

Abstract

Psoriatic disease is a heterogeneous condition that can affect peripheral and axial joints (arthritis), entheses, skin (psoriasis) and other structures. Over the past decade, considerable advances have been made both in our understanding of the pathogenesis of psoriatic disease (PsD) and in the treatment of its diverse manifestations. However, several major areas of continued unmet need in the care of patients with PsD have been identified. One of these areas is the prediction of poor outcome, notably radiographic outcome in patients with psoriatic arthritis, so that stratified medicine approaches can be taken; another is predicting response to the numerous current and emerging therapies for PsD, so that precision medicine can be applied to rapidly improve clinical outcome and reduce the risk of toxicity. In order to address these needs, novel approaches, including imaging, tissue analysis and the application of proteogenomic technologies, are proposed as methodological solutions that will assist the dissection of the critical immune-metabolic pathways in this complex disease. Learning from advances made in other inflammatory diseases, it is time to address these unmet needs in a multi-centre partnership aimed at improving short-term and long-term outcomes for patients with PsD.

The power and potential of BIOMAP to elucidate host‐microbiome interplay in skin inflammatory diseases

“…The intelligent integration of 'omics' data with detailed clinical, environmental and lifestyle information has the potential to identify the molecular identity and subclasses of the underlying disease aetiologies. 25,26 Yet generating,…”

Nail disease in psoriatic arthritis. Data from the Russian Psoriatic Arthritis Registry

“…Результаты нашего исследования, как и данные других авторов, подтверждают необходимость прицельной диагностики Пс ногтей и оптимизации методов лечения, в том числе таргетной терапии, что позволит улучшить течение и прогноз ПсА в целом. В дальнейшем требуется провести более детальный анализ фармакотерапии, а также клиническое и молекулярно-генетическое фенотипирование данной категории пациентов [25]. Раннее внедрение активного лечения позволит воздействовать на все терапевтические мишени при ПсА: энтезисы, синовию, кожу и ногти.…”

From Bed to Bench and Back: TNF-α, IL-23/IL-17A, and JAK-Dependent Inflammation in the Pathogenesis of Psoriatic Synovitis

“…Infiltration of both innate and adaptive immune cells in different target organs and tissues results in significant production of different proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-22, IL-23, IL-17A, and IL-18, inducing further inflammatory mediators release and damage progression. New evidence in PsA pathogenesis has provided further insights into the molecular pathways involved in either cutaneous or articular manifestations of the disease, and genetic, epigenetic, environmental, cellular, and molecular aspects have been clarified, driving the development of different targeted therapies ( Jadon et al, 2020 ). From a clinical point of view, drugs targeting different molecules primarily involved in chronic inflammation, such as TNF-α, the IL-23/IL-17A axis, or Janus kinases/signal transducers and activators of transcription (JAK/STATs), are now available ( Gossec et al, 2016 , 2020 ; Singh et al, 2018 ).…”

“…A priori, tissue-specific biomarkers are the most promising candidates to stratify patients based on the actual ongoing pathogenic process and are suitable for targeting by pharmacological treatments, as demonstrated by some attempts in other chronic inflammatory joint diseases, such as rheumatoid arthritis (RA) ( Humby et al, 2021 ). Despite important discoveries in this field, there are still great obstacles to the goal of “personalized arthritis medicine’ in the context of PsA ( Jadon et al, 2020 ).…”

“…Despite the growing number of studies aimed at identifying diagnostic, prognostic, and treatment selection biomarkers ( Generali et al, 2016 ; Mahendran and Chandran, 2018 ; Mahmood et al, 2018 ), no validated biomarkers are yet available for clinical use in PsA ( Scher et al, 2019 ). Special interest lies in identifying peripheral blood, synovial fluid (SF), and synovial membrane biomarkers of response to drugs with different mechanisms of action ( Jadon et al, 2020 ).…”