Psoriatic disease treatment nowadays: unmet needs among the “jungle of biologic drugs and small molecules”

Excerpt

Rheumatology is the branch of medicine dealing with the diagnosis and treatment of articular and connective tissue diseases. Outstanding progresses have been done in the last few decades regarding diseases pathogenesis and new diagnostic processes as well as innovative therapies [1]. Indubitably, the evolution in psoriatic arthritis (PsA) knowledge represents an emblematic example [2]. Indeed, fundamental advances in understanding PsA pathogenesis and natural history have deeply changed its perception by both patients and physicians [3]. In the past, psoriasis was considered just a mere esthetic concern due to a primary defect in keratinocytes, leading to their hyper-proliferation. Nowadays, it is well known that psoriasis and PsA have to be considered a systemic disease, not limited to the skin and joints, but linked to increased cardiovascular risk, obesity, and metabolic syndrome through a shared chronic pro-inflammatory background, establishing the concept of psoriatic disease (PsD) [4]. PsD often requires a multidisciplinary approach through the collaboration of dermatologist, rheumatologist, immunologist, etc. [5]. In addition, being a chronic inflammatory multifactorial disease and dysregulation of immune cells (Th1 and Th17 above all) have been reported as key features of PsD pathogenesis [6]. In this context, a major role is played by inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-17, IL-22, and IL-23 [6, 7]. Advances in PsD pathogenesis have put the basis for the development of new effective drugs for its treatment. Particularly, monoclonal antibody and fusion protein able to inhibit the effects of pro-inflammatory cytokines involved in PsD development, the so-called biologic drugs, have completely revolutionized disease management [8]. It is relevant, for example, that 40 years ago topical treatments such as corticosteroid, salicylic acid, and coal tar represented the main stay of psoriasis therapies, whereas nowadays different new systemic drugs are available such as biologics like anti-TNF-α (adalimumab, etanercept, golimumab, certolizumab, infliximab), anti-IL-12–23 (ustekinumab), and anti-IL-17 (ixekizumab, secukinumab) [8‐10]. Moreover, literature is constantly enriching of clinical trials and surveys regarding newer biologic drugs which will be soon available for psoriasis and PsA treatment such as anti-IL-17 receptor (brodalumab) [11], anti-IL-23 (guselkumab, tildrakizumab) [12, 13], and anti-CD6 (itolizumab) [14]. However, PsD treatment scenario is going to become more and more complex and wide apart from the development of biologic drugs. A new era will be introduced by the so-called small molecules which are able to act at the basis of the pro-inflammatory cascade which dominates PsD pathogenesis, preventing the production of inflammatory cytokines. This is the case of molecules such as phosphodiesterase 4 (PDE4) inhibitor (apremilast) and Janus kinase (JAK) inhibitor (tofacitinib) [15]. …