About 2.5 million people in Italy live with immune-mediated diseases such as psoriasis and psoriatic arthritis. These two conditions have a common link: an imbalance in the immune system that leads to chronic inflammation. In fact, up to 30 percent of those who suffer from the former can develop the latter. “There is no cure for psoriasis, but there are therapies by which it is possible to control the clinical manifestations of the disease, allowing long periods of remission. More than half of people with psoriasis also live with other diseases, such as diabetes, some heart diseases and depression “, explains Ketty Peris, Full Professor of Dermatology, Director of UOC Dermatology, Agostino Gemelli University Hospital Foundation IRCCS Catholic University of Sacro Cuore, Rome and President of the Italian Society of Medical, Surgical, Aesthetic Dermatology and Sexually Transmitted Diseases – SIDeMaST.
Psoriatic arthritis causes pain, stiffness and swelling in the joints; it commonly occurs between the ages of 30 and 50 but can develop at any age. In patients with psoriatic arthritis, comorbidities such as obesity, cardiovascular disease, inflammatory bowel disease, anxiety and depression are often present. “Although the cause of psoriatic arthritis is unknown, genetic predisposition, impaired immune system and some environmental factors are thought to play a role in the onset of the disease,” continues Peris.
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The selective action
A mechanism common to the two diseases is the activation of a cascade of inflammatory events in which specific molecules, cytokines, are involved. Indicated by numbers, cytokines are the engine of inflammation. “The discovery of IL-23, as a specific immunological mechanism of psoriasis and psoriatic arthritis, has made it possible in recent years to develop very precise drugs against this target”, explains Carlo Francesco Selmi, Head of Clinical Rheumatology and Immunology Unit, IRCCS Clinical Institute Humanitas, Rozzano and professor of Humanitas University.
One of these is guselkumab, the first fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 blocking its effects without affecting those of other inflammatory cytokines such as, for example, IL-12 and IL-17 which are, instead, important for the body’s defense against pathogens. This means that even when IL-23 is inhibited, immune responses can still take place. In Italy, guselkumab is currently reimbursed by the National Health System in the indication of plaque psoriasis. “The inhibition of IL-23 prevents the reactivation of so-called resident memory T cells, TRM cells, which are found in the skin of patients treated with any drug effective in psoriasis. Today, however, we know that the presence of a trigger factor and IL-23 generates the reactivation of TRM cells with consequent production and release of pro-inflammatory cytokines “, explains Giovanna Malara, UOC Director of Dermatology, Grande Metropolitan Hospital of Reggio Calabria . “A recent sub-analysis of the Eclipse study showed that inhibiting IL-23, and not IL-17, would prevent this phenomenon and therefore significantly reduce disease flares.”
Also useful in psoriatic arthritis
“The availability of a drug capable of selectively blocking IL-23, already used effectively by fellow dermatologists for the treatment of psoriasis, will allow a treatment of the various manifestations of psoriatic arthritis with a safety profile that is now well understood”, says Selmi . “The two-year data presented recently at the congress of the American Society of Rheumatology confirm the stability of the response both on inflammation of the joints and on that of other sites of disease. Some studies also suggest that blocking IL-23 may also improve the asthenia and pain associated with psoriatic arthritis. In light of these data, the GRAPPA and European recommendations also place guselkumab at the forefront, like drugs that target TNFalpha and IL-17, in the treatment of psoriatic arthritis candidate for biological therapy “, adds Selmi.
The impact on the quality of life
Living with these diseases has an important impact on the quality of life: they are debilitating, chronic, they can cause pain with the inability to carry out daily activities and in many cases they are accompanied by comorbidities, including depression. “Today, with the advent of therapies aimed at particular immunological targets, such as cytokines, it is possible to achieve clinical remission or, alternatively, minimal disease activity. These two therapeutic objectives are of fundamental importance for patients, as they allow an improvement in the quality of life “, concludes Ennio Lubrano, Full Professor of Rheumatology, University of Molise, Campobasso.
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