TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis

Wcisło‐Dziadecka, Dominika; Zbiciak-Nylec, Martyna; Brzeźińska-Wcisło, Ligia; Mazurek, Urszula

doi:10.1136/postgradmedj-2015-133419

Cited by 22 publications

(16 citation statements)

References 24 publications

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“…If an adequate response is not obtained, treatments may be augmented or replaced with bDMARDs or tsDMARDs. The bDMARDs and tsDMARDs are associated with improved clinical outcomes, quality of life and functioning in patients with inflammatory arthritis [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

What do Australian patients with inflammatory arthritis value in treatment? A discrete choice experiment

Acar²,

Puig³

et al. 2019

Clin Rheumatol

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Background and objectives The purpose of this study was to develop an understanding of treatment preferences in patients with inflammatory arthritis (IA) [rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA)] focussing on treatment attributes that patients' value, their relative importance, and the risk-benefit trade-offs that characterise patients' choices around treatment. Methods A discrete choice experiment (DCE) approach was used. Attributes of interest were clinical efficacy; slowing of disease progression; risk of mild-moderate side effects; risk of severe side effects; frequency of administration; real-world product evidence; management of related conditions; and availability of a patient support programme. Using data from the DCE component, a restricted latent class model (LCM) was estimated to determine discrete 'classes' of treatment preferences. Results In this analysis, 206 participants were included (AS n = 59; PsA n = 62; RA n = 85). Two classes were identified. For 'class 1' (59.9%), the most important attributes (across all treatment modalities) were preventing disease progression, clinical efficacy and risk of mild-to-moderate side effects. For 'class 2' (40.1%), clinical and non-clinical attributes were important, and attribute importance depended on treatment modality. Patient demographic and treatment characteristics did not predict class membership. Conclusion For most patients with IA, clinical efficacy, stopping disease progression and risks of mild-to-moderate side effects are important treatment attributes. Patients with prior biologic DMARD experience had greater preference for injection treatments. For a subset of patients, patient support programmes and the frequency of administration were important. Clinicians should be mindful of preferences when prescribing treatment to patients with IA. Key Points • Most patients consider clinical efficacy, stopping disease progression and the risk of mild-to-moderate side effects as important treatment attributes • Patients with prior biologic DMARD experience have greater preference for injection treatments. • For a subset of patients, patient support programmes, and the frequency of administration were important. • Clinicians should be mindful of preferences when prescribing treatment to patients with IA.

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Section: Introductionmentioning

confidence: 99%

What do Australian patients with inflammatory arthritis value in treatment? A discrete choice experiment

Acar²,

Puig³

et al. 2019

Clin Rheumatol

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“…Currently, treatment perspectives include the blocking of the TNF, IL‐23 and IL‐17/17R pathway (chronic psoriasis), the use of cyclosporine, UV light, steroids, vitamin D or blocking of interferon/plasmacytoid dendritic cell pathway (acute psoriasis) or the use of cyclosporine, infliximab, retinoids, methotrexate or blocking of the IL‐1 and IL‐36 pathway (pustular psoriasis) …”

Section: Inflammatory Skin Diseases: Complex Network and Molecular Tmentioning

confidence: 99%

Molecular and cellular discoveries in inflammatory dermatoses

Soumelis

2017

Acad Dermatol Venereol

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It was no earlier than 1986 that T helper (Th)1 and Th2 cells were described for the first time, opening the field of lymphocyte diversity and the investigation of the physiopathology of inflammatory diseases such as atopic dermatitis and psoriasis. Since that time, much research has been carried out showing a very complex communication network leading to inflammatory responses. Nowadays, understanding the cellular and molecular components of the inflammatory network and of the different crosstalks not only for groups of diseases but also for the individual patient is mandatory for developing and personalizing treatments. The aim of the present proceeding was to provide an update concerning some of the most recent molecular and cellular discoveries in inflammatory skin diseases and especially of AD.

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“…[ ] The clinical relevance namely of TNF‐α, IL‐17A and IL ‐ 23 is reflected by the high efficacy of antibodies blocking these cytokines in the treatment of psoriasis. [ ]…”

Section: Introductionmentioning

confidence: 99%

The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development

Stalder

Zhang

Wrobel

et al. 2019

Experimental Dermatology

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Several cytokines signalling via Janus Kinase (JAK) proteins have been implicated in the pathogenesis of immune‐mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). Tofacitinib, a small JAK inhibitor, is approved for the treatment of RA and has demonstrated good efficacy in psoriasis phase III clinical trials. In this work, we analysed the in vitro effects of tofacitinib on the functions of human dendritic cells (DCs) and macrophages. When assessing the effects of tofacitinib on monocyte‐derived DCs, we observed reduced differentiation of monocytes into immature DCs, as evidenced by a decreased transcription of CD209 and CD80. Phenotype assessment in the presence of tofacitinib suggested a switch towards a M1‐like macrophage phenotype, as evidenced by the expression of M1 markers such as iNOS, as well as cytokines typically expressed by M1 cells, including IL‐12 and IL‐23. Of note, Arginase1 and CD200R, typically expressed by M2 cells, were absent on tofacitinib‐treated DCs. Furthermore, tofacitinib affected the response of differentiated DCs to maturation stimuli such as LPS and IFNγ, resulting in a partial up‐regulation of IL‐23 and down‐regulation of IL‐12, as assessed by qPCR. When investigating macrophage development, we found that tofacitinib inhibited the ability of monocytes to differentiate and polarize into regulatory M2 macrophages, while rather enhancing the ability to develop into inflammatory M1‐like macrophages, as evidenced by decreased expression of the M2 marker CD200R and enhanced production of IL‐12 and IL‐23. In conclusion, tofacitinib impacts the differentiation of human DCs and macrophages, it particularly favours generation of M1‐like pro‐inflammatory macrophages.

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TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis

Cited by 22 publications

References 24 publications

What do Australian patients with inflammatory arthritis value in treatment? A discrete choice experiment

What do Australian patients with inflammatory arthritis value in treatment? A discrete choice experiment

Molecular and cellular discoveries in inflammatory dermatoses

The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development

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