Psoriasis is an inflammatory skin disease with a chronic relapsing course and an often-detrimental impact on patients’ quality of life. Thanks to incredible advances in research over the past few decades, the therapeutic armamentarium of psoriasis is now reasonably broad and structured, with several therapeutic agents that have demonstrated successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of existing ones. A great deal of attention has recently been paid to the JAK/STAT pathway, playing a crucial role in chronic inflammatory skin diseases, including psoriasis. Indeed, in a disease with such a complex pathogenesis, the possibility to antagonize multiple molecular pathways via JAK/STAT inhibition offers an undeniable therapeutic advantage. However, data from clinical trials evaluating the use of oral JAK inhibitors in immune-mediated disorders, such as RA, have arisen safety concerns, suggesting a potentially increased risk of class-specific AEs such as infections, venous thromboembolism, and malignancies. New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis.

Background/Objectives: Psoriasis (PsO) is a chronic inflammatory skin disease that severely impacts patients’ quality of life (QoL). Its global prevalence is about 2%, with significant regional variations. PsO manifests in the form of erythematous and scaly plaques, causing intense pruritus and discomfort and limiting daily activities. The condition often includes comorbidities such as psoriatic arthritis, cardiovascular diseases, and metabolic syndrome, further deteriorating QoL. Psychological well-being is notably affected, with high levels of depression and anxiety due to the visible lesions, leading to social stigma and isolation. QoL indexes like WHO-QoL and SF-36 assess various well-being aspects, while patient-reported outcomes (PROs) provide a comprehensive understanding of PsO’s impact. However, there are no universally shared PROs in outpatient practice to fully understand the impact of the disease and associated therapies. This study aims to evaluate differences between DLQI and WHO-5 in adult patients with moderate-to-severe PsO treated with tildrakizumab 100 mg or 200 mg. Methods: The study was conducted at the University Hospital of Siena, Italy, from May 2023 to April 2024. Data from 15 patients treated with tildrakizumab 200 mg and 15 patients treated with tildrakizumab 100 mg, observed for at least 28 weeks, were recorded. Demographic data, PASI, DLQI, and WHO-5 scores were analyzed. Patients in the 100 mg group (G100) were selected to match the demographic characteristics of the 200 mg group (G200). Reduction rates of DLQI and WHO-5 were assessed at baseline values and after 4, 16, and 28 weeks. Results: Both groups experienced improvements in QoL. The group treated with 200 mg showed more pronounced and rapid reductions in DLQI and WHO-5 scores compared to the 100 mg group. WHO-5 demonstrated faster improvements in overall well-being than DLQI, indicating its greater sensitivity to changes in mental well-being and overall QoL. No differences in adverse events were observed between the two groups, with no major adverse events reported. Conclusions: In our study, WHO-5 proved more sensitive than DLQI in capturing well-being changes in PsO patients treated with tildrakizumab. However, a combined use of both WHO-5 and DLQI questionnaires should be encouraged in clinical practice. Furthermore, this study confirmed the superior QoL improvement associated with tildrakizumab 200 mg compared to 100 mg. Future research should explore the long-term impact on QoL and comparative effectiveness among other biologic therapies in diverse patient populations.

Article: Bullous pemphigoid induced by adalimumab in a patient with psoriasis - Italian Journal of Dermatology and Venereology 2024 Nov 13 - Minerva Medica - Journals