Psoriasis is a chronic autoimmune skin disease that is suffered by around 125 million people around the world and one million people in Spain, according to data from the Spanish Association of Dermatology and Veneorology (AEDV), and which has a significant impact on the lives of those affected and influences their social relationships, self-esteem, sexuality and emotional and psychological well-being. Now, Spanish patients will have deucravacitnib (Sotyktu®), a new drug that will expand their therapeutic options.
It is the first and only approved and marketed tyrosine kinase 2 (TYK2) inhibitor administered orally once daily to treat moderate to severe plaque psoriasis in adults candidates for systemic therapy, and has been included in the pharmaceutical provision of the National Health System (SNS) after having obtained approval from the European Commission.
Deucravacitnib has been developed by the biopharmaceutical company Bristol Myers Squibb (BMS) and has demonstrated that its long-term efficacy is similar to that of first-generation biological treatments. During the presentation of the drug, José Cabrera, Medical Director of BMS Spain & Portugal, wanted to highlight that “there is a need for oral therapies that reinforce long-term effectiveness and with a good safety-tolerability profile that provide significant skin cleansing. and improve the quality of life of patients. With deucravacitinib we have an oral treatment that achieves the therapeutic objective that we sought with conventional biological treatments.”
Patients with psoriasis have a higher risk of developing other chronic pathologies such as psoriatic arthritis, metabolic syndrome, cardiovascular disorders, anxiety, depression, non-alcoholic fatty liver, Crohn’s disease or lymphoma. For this reason, Dr. Pablo de la Cueva, Head of the Dermatology Service at the Infanta Leonor University Hospital (Madrid) and Secretary of the Psoriasis Group (GPs) of the AEDV, has pointed out that “care for patients with psoriasis requires not only “To treat skin lesions and joint involvement, it is also important to identify and treat comorbidity that already exists or may develop, whether cardiovascular diseases, metabolic diseases or psychological conditions.”
How the new drug against psoriasis works
Deucravacitnib is an inhibitor of tyrosine kinase 2 (TYK2), one of the molecules of the immune system that plays an important role in transmitting signals throughout the body with the aim of protecting us from infections and diseases. These signals help form new skin cells only when and where they are needed. In psoriasis, TYK2 passes too many signals and this can cause inflammation and cause its accumulation in the skin and the formation of plaques.
Bristol Myers Squibb scientists designed deucravacitinib to selectively target TYK2, thereby inhibiting the signaling of interleukin (IL)-23, IL-12, and type 1 interferons (IFNs), key cytokines involved in pathogenesis. of various immune-mediated diseases. The specific allosteric binding of deucravacitinib to the regulatory domain of TYK2 causes it to block exclusively TYK2.
Trials also demonstrate the effectiveness of deucravacitinib in difficult-to-treat areas, such as the scalp, palmoplantar area, or ungual involvement.
This innovative mechanism of action, as explained by Dr. Anna López, assistant Dermatology Service at the Sant Pau Hospital (Barcelona) and coordinator of the Psoriasis Group (GPs) of the AEDV, “is a treatment option with respect to biological drugs, and in patients without an adequate response or in whom conventional therapy is not recommended, or after conventional systemic treatment when this is indicated and there is no contraindication. It does not require escalation or dose adjustment in special populations (advanced age, renal or hepatic insufficiency). In addition, it has a short half-life, so if the patient needs to interrupt treatment, in case of gestational desire or need for surgical intervention, it is easily manageable.”
The phase 3 Poetyk PSO-18, Poetyk PSO-29 clinical trials, which have compared the efficacy and safety of deucravacitinib against placebo and the most recently marketed oral treatment in adult patients with moderate-severe psoriasis, have shown that treated patients with deucravacitinib they achieved a significantly higher PASI 75 and PASI90 response at week 16.
On the other hand, the trials also demonstrate efficacy in areas that are difficult to treat, such as the scalp, palmoplantar area or nail involvement: seven out of 10 patients with scalp involvement achieved complete or almost complete clearance. At week 16, almost six out of 10 patients with palmoplantar involvement achieved complete or near-total clearance at week 24 and almost five out of 10 patients with nail involvement achieved a PGA-F 0/1 response at week 52.
