Could Targeted Pharmacotherapies Exert a “Disease Modification Effect” in Patients with Chronic Plaque Psoriasis?

Abstract

Chronic plaque psoriasis is an immune-mediated skin disease with a chronic relapsing course, affecting up to ~2–3% of the general adult population worldwide. The interleukin (IL)-23/Th17 axis plays a key role in the pathogenesis of this skin disease and may represent a critical target for new targeted pharmacotherapies. Cutaneous lesions tend to recur in the same body areas, likely because of the reactivation of tissue-resident memory T cells. The spillover of different pro-inflammatory cytokines into systemic circulation can promote the onset of different comorbidities, including psoriatic arthritis. New targeted pharmacotherapies may lead to almost complete skin clearance and significant improvements in the patient’s quality of life. Accumulating evidence supports the notion that early intervention with targeted pharmacotherapies could beneficially affect the clinical course of psoriatic disease at three different levels: (1) influencing the immune cells infiltrating the skin and gene expression, (2) the prevention of psoriasis-related comorbidities, especially psoriatic arthritis, and (3) the improvement of the patient’s quality of life and reduction of cumulative life course impairment. The main aim of this narrative review is to summarize the effects that new targeted pharmacotherapies for psoriasis may have on the immune scar, both at the molecular and cellular level, on psoriatic arthritis and on the patient’s quality of life.

Current developments and perspectives in psoriasis

“…In addition, small‐molecule drugs have been and are being developed, for example, apremilast against phosphodiesterase 4 (PDE4), deucravacitinib against tyrosine kinase 2 (TYK2), and piclidenoson, a Gi protein‐associated A3 adenosine receptor agonist (Figure 1, Table 1). 40 It is conceivable that some modern therapies may even lead to fundamentally altered and normalized immune status (disease modification) and thereby to permanent remission of psoriasis, at least in some patients 42 . Compared with the era before biologics, one can certainly speak of a revolution.…”

“…40 It is conceivable that some modern therapies may even lead to fundamentally altered and normalized immune status (disease modification) and thereby to permanent remission of psoriasis, at least in some patients. 42 Compared with the era before biologics, one can certainly speak of a revolution.…”

Aktuelle Entwicklungen und Perspektiven bei Psoriasis

“…40 Möglicherweise führen manche moderne Therapien sogar zu grundlegend veränderter und normalisierter Immunlage (disease modification) und dadurch zu dauerhafter Remission der Psoriasis, zumindest bei manchen Patienten. 42 Verglichen mit der Ära vor den Biologika kann man durchaus von einer Revolution sprechen.…”

“…Darüber hinaus wurden und werden niedermolekulare Arzneimittel entwickelt, beispielsweise Apremilast gegen Phosphodiesterase 4 (PDE4), Deucravacitinib gegen Tyrosinkinase 2 (TYK2) und Piclidenoson, ein Gi‐Protein‐assoziierter A3‐Adenosinrezeptor‐Agonist (Abbildung 1; Tabelle 1). 40 Möglicherweise führen manche moderne Therapien sogar zu grundlegend veränderter und normalisierter Immunlage (disease modification) und dadurch zu dauerhafter Remission der Psoriasis, zumindest bei manchen Patienten 42 . Verglichen mit der Ära vor den Biologika kann man durchaus von einer Revolution sprechen.…”

The transition from mild to moderate‐to‐severe chronic plaque psoriasis

“…Dear Editor, The clinical course of psoriasis is unpredictable, and the proportion of patients with mild psoriasis at onset who progress to moderate-to-severe disease is unclear. 1 The objective of this study was to investigate the transition from mild to moderate-to-severe psoriasis and to identify risk factors. We conducted a retrospective, observational cohort study involving adult patients consecutively visited at the Hospitals of Verona and Padua between January 2005 and 2020.…”