Efficacy and safety of deucravacitinib for the management of psoriasis: a drug safety evaluation.

INTRODUCTION: Nowadays, despite the wide availability of biological drugs and apremilast for psoriasis management, there is always a need for new therapies to customize the therapeutic approach on the basis of the patient's clinical features and comorbidities, especially in order to achieve a prolonged therapeutic response. Thus, new treatment strategies are required to offer patients a personalized approach. In this scenario, major knowledge on psoriasis pathogenesis led to the development of deucravacitinib, an orally administered selective TYK2 inhibitor. AREAS COVERED: The aim of this manuscript is to review the current literature on the effectiveness and safety of deucravacitinib in psoriasis to offer readers a wide perspective. The current English literature was analyzed using the PubMed, Google Scholar, Embase, Cochrane Skin, and clinicaltrials.gov databases, selecting the most relevant manuscripts. EXPERT OPINION: Deucravacitinib appears to be an innovative weapon for the management of moderate to severe psoriasis. Despite its efficacy and safety profiles have been revealed by RCTs, real-life data are still scant. Certainly, deucravacitinib broadens the range of therapeutic alternatives for psoriasis patients, thus enhancing the holistic and personalized approaches required for the treatment of this disease.

Management of Psoriasis Patients with Serious Infectious Diseases.

The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.

The Role of Interleukin 23/17 Axis in Psoriasis Management: A Comprehensive Review of Clinical Trials.

Psoriasis pathogenesis is influenced by genetic factors and characterized by a complex interplay between genetic predisposition and various environmental triggers. These triggers set off metabolic processes involving inflammation, cell signaling, immune response dysregulation, and antigen presentation. Several types of innate and adaptive immune cells are involved in psoriasis. Among the cytokine cascade which leads to psoriasis development, the interleukin (IL)-23/Th17 axis, especially IL-17 production, emerges as crucial. Recognizing the pivotal role of this axis has facilitated the development of selective and effective biological drugs, such as anti-IL17 and anti-IL23 monoclonal antibodies. These drugs aim to achieve the complete or near-complete disappearance of psoriatic lesions, as indicated by PASI100 and PASI90 responses, respectively. In this context, the aim of our review was to delve into the functioning of the IL-23/Th17 axis, its dysregulation in psoriasis pathogenesis, and the therapeutic potential of its inhibition. Currently, 4 anti-IL17 (secukinumab, ixekizumab, bimekizumab and brodalumab) and 3 anti-IL23 (guselkumab, risankizumab and tildrakizumab) have been approved. All these drugs showed high levels of effectiveness in both clinical trials and real-life experiences, with an excellent profile in terms of safety. Certainly, furthers studies will allow for better characterization of biologics' profile, in order to administer the right drug for the right patients at the right moment.

Psoriasis and Molecular Target Therapies: Evidence of Efficacy in Preventing Cardiovascular Comorbidities.

Psoriasis is now considered a systemic disease, and several comorbidities have been described such as cardiovascular diseases, neurologic and psychiatric disorders, chronic inflammatory bowel disease, psoriatic arthritis, etc. Regarding cardiovascular comorbidities, major adverse cardiovascular events have been reported in psoriasis patients by multiple epidemiologic studies. Moreover, smoking, obesity, metabolic syndrome, hypertension, dyslipidemia, diabetes and reduced physical activity are associated with psoriasis, increasing cardiovascular risk. Consequently, several aspects should be considered when making the treatment decision. The aim of this review manuscript was to investigate the effectiveness and safety of biologic drugs acting on molecular mechanisms involved in the pathogenesis of psoriasis in preventing cardiovascular complications.

Topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) for lichen sclerosus of face: case report and literature review.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis typical of the genital region, with rare involvement of extragenital areas and particularly the face. LS therapeutic management is challenging, and common therapies including topical and systemic corticosteroids, topical calcineurin inhibitors, surgery are often ineffective. Herein, we present a case of LS occurred in a 36-year-old girl with facial involvement resistant to therapy with systemic corticosteroids and topical tacrolimus. Considering the involvement of a sensitive area, the young age of the patient, and the consistent clinical experience in using photodynamic therapy for the treatment of facial skin disease, we started a treatment with topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) with a dosage of 37 J/cm2 once a month. We compared our case with eight other facial LS patients from the literature and treated differently.

A Case of Erythrodermic Psoriasis Successfully Treated with Risankizumab.

Psoriasis is a chronic inflammatory cutaneous disease, affecting up to 3% of the worldwide population. Several clinical phenotypes can be distinguished. Among these, erythrodermic psoriasis (EP) is a rare and severe variant (less than 3% of cases), characterized by severe generalized erythema and scaling affecting at least 90% of the body surface area. EP is often a life-threatening condition, since several systemic symptoms (tachycardia, fever, fatigue, lymphadenopathy, dehydration, serum electrolyte disturbances) can be associated. Thus, a prompt and appropriate treatment is mandatory. Unfortunately, EP treatment is challenging. Indeed, the reduced prevalence of EP makes clinical trials feasibility difficult, leading to the absence of established guidelines. So, the treatment of EP is often derived from moderate-to-severe psoriasis management which relies on the use of conventional systemic drugs (cyclosporine, dimethyl fumarate, methotrexate, retinoids) and biologic agents. However, conventional systemic drugs are often contraindicated for patients' comorbidities, or their use is characterized by reduced efficacy and various adverse events (AEs). The recent development of biologic drugs, which showed excellent results in terms of effectiveness and safety in plaque psoriasis, made these drugs an ideal weapon in EP management, despite their use in EP is still off-label. Among these, risankizumab, a humanized immunoglobulin G1 monoclonal antibody targeting the p19 subunit of the IL23, is one of the latest biologics approved for the management of moderate-to-severe psoriasis. Herein, we reported the first case of a caucasian patient affected by EP successfully treated with risankizumab, reaching PASI100 response after 16 weeks of treatment, without experiencing AEs.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.