Psoriatic arthritis: advances in pharmacotherapy based on molecular target

Abstract

The progress on the improved understanding of disease pathogenesis and molecular biology has changed the understanding of disease profiles, emphasizing aspects that simple clinical observation could not identify, and demarcating differences between clinical pictures that seemed to overlap. An example of this spectacular evolution is represented by psoriatic arthritis (PsA). This increase of knowledge on pathogenesis has led to an important impact on therapeutic approach. Therapies are now taken into account because their precise target is known. The authors describe treatment guidelines and revisit traditional therapies as well as innovative therapies in PsA.

Keywords::

• anti-TNF-α
• psoriatic arthritis
• psoriatic disease
• tailored therapy

The progress on the improved understanding of disease pathogenesis and molecular biology has been the main factor in influencing the therapeutic approach to various diseases within general medicine.

This new perspective has also changed the understanding of disease profiles, emphasizing aspects that simple clinical observation could not identify, and demarcating differences between clinical pictures that seemed to overlap. An example of this spectacular evolution is represented by psoriatic arthritis (PsA).

The progress in improved knowledge on pathogenesis of PsA has allowed us to identify the critical importance of the action of several inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-23 and IL-17 [1-3] – an area that has seen an impressive development of evidence for this therapeutic target [4-9].

First, it has generated a better understanding of what is today called “psoriatic disease” (PsD). This is a systemic condition in which the increase of activity of TNF-α acts as one of the most important driver for a series of interactions. These lead not only to the genesis of skin and joints manifestations but also to other conditions such as inflammatory bowel disease, metabolic syndrome manifestations and accelerated atherosclerosis [10,11]. In other words, the recognition of the pathogenetic mechanism brings much unity to a diverse variety of clinical conditions.

At the same time, such knowledge helps to demarcate PsD from other kinds of arthritis, the boundaries of which not infrequently tend to overlap, generating gray areas that can now be more clearly identified. In addition, it is now clear from these boundaries that PsD continues to be regarded as different from rheumatoid arthritis, and that categorization within the area of seronegative spondyloarthropathies is also becoming clarified.

In addition, the increase of knowledge on pathogenesis has led to an important impact on therapeutic strategies. Newer therapies are of course developed to inhibit precise targets, even if these can remain hidden in PsA. Thus, the advances have taken into consideration to target the IL-12/23 pathway. Ustekinumab, a human monoclonal antibody directed against the common p40 chain of both IL-12 and IL-23, is used for the treatment of psoriasis, and it has also been shown to improve articular signs and symptoms in PsA patients [8].

Other therapeutic targets were IL-6 and T cells; in fact, IL-6 influences T-cell development into Th17 cells, which are important mediators in PsA [3]. Abatacept, a CTLA4-IgG fusion protein, has been shown effective on joints with a less effect on skin lesions [9].

Therefore, the pathogenetic action is more and more focused, and the expectation of the scientific community has been increasingly drawn to the acquisition of evidence on the precise mechanism of action of the drugs used.

This approach, along with a renewed review of the complex interaction of the different pathogenetic cascades also opens the way for a more focused use of the different drugs available. In addition, this could herald combined or sequential therapy in the future [12,13]. The next and most likely hypothesis is, for example, the possibility to use two biological agents simultaneously to exploit their best features. This approach might be used not only in individuals resistant to a first drug but also in situations in which the expression of the different components of the PsD is so marked as to suggest the use of two or more agents with different actions.

Sequential therapy itself becomes in this context a topic of extreme importance. This is because it not only increases the number of patients in whom the disease (having reached a low intensity) requires a less pressing control, but also because the same therapeutic action in many cases determines changes in the cytokine profile, requiring periodical adjustments of therapeutic targets.

With the background of the aspects mentioned remains the important question of the screening required for access to such therapies, and the need for their close monitoring. On these matters, the attention of the scientific community is growing in a most interesting way. And foremost is the growing message concerning the importance of responsible monitoring [14].

These considerations introduce the article “Psoriatic arthritis: current therapy and future directions” by D Huynh and A Kavanaugh recently published in the Journal [15].

The authors, starting from a clinical characterization of psoriatic arthritis, describe treatment guidelines and revisit traditional therapies as well as innovative therapies, including those in which the targets differ from TNF-α.

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.