Novel pharmacotherapies and breakthroughs in psoriasis treatment: 2024 and beyond.

INTRODUCTION: The use of the current available therapies for psoriasis management may sometimes be limited by reduced patients' compliance, safety issues for patients' comorbidities, primary lack of efficacy, loss of effectiveness, development of side effects. In this context, several clinical trials investigating the use of both topical and systemic therapies are ongoing, and other new drugs will be approved soon. AREAS COVERED: The aim of this manuscript is to review current literature and to provide an overview of the current and future trends in psoriasis treatment. A comprehensive review of the English-language medical literature was performed using Pubmed and clinicaltrials.gov databases. EXPERT OPINION: Although several therapies are currently available for psoriasis' treatment, unmet needs still exist for patients with moderate and severe psoriasis and hence expanding the therapeutic armamentarium is desirable for a more personalized approach. The ongoing development of innovative therapies could provide effective and safe therapies in the future enhancing the therapeutic management of moderate-severe unresponsive psoriasis.

Secukinumab for Severe Hidradenitis Suppurativa in a Patient on Haemodialysis: Efficacy and Safety on 300 mg Every 2 Weeks Administration - A Case Report.

This case study outlines the management of a 24-year-old male with a history of juvenile nephronophthisis who underwent renal transplantation at age 12 and later required dialysis at 18 due to chronic rejection and hypertension. Subsequently, the patient developed severe Hidradenitis Suppurativa (HS) affecting the axillary, groin, and gluteal regions. Despite undergoing various systemic and intravenous antibiotic therapies, as well as Adalimumab treatment, the HS remained refractory. Adalimumab was discontinued due to a detected ejection fraction of 45% during cardiologic follow-up, likely due to COVID-19 related myocarditis. Following this, the patient was initiated on secukinumab therapy, initially undergoing an induction phase followed by maintenance dosing. Significant improvements were observed in quality of life, pain scores, and HS activity after 5 weeks of secukinumab therapy, with sustained benefits at the 6-month follow-up. Secukinumab was well tolerated, with no reported adverse events. This case underscores the effectiveness and safety of secukinumab as a therapeutic option for refractory HS, particularly in patients with comorbidities such as renal transplant recipients.

Risk Factors for Psoriasis Flares: A Narrative Review.

Psoriasis is a chronic inflammatory cutaneous disease with multifactorial pathogenesis involving both genetic and environmental factors as well as the innate and acquired immune response. Several triggering factors may exacerbate or worsen the disease. In this context, we performed a review manuscript with the aim of investigating current literature on psoriasis risk factors, also showing possible mechanisms by which they act on psoriasis. Globally, risk factors can be divided in classic risk factors (eg, mechanical stress, infections and dysbiosis of the skin, common drugs, environment and pollution, lifestyle, psychological stress, hormonal and metabolic alterations) which have long been known to be responsible for worsening and/or reoccurrence of psoriatic manifestations, and emerging risk factors (eg, biological drugs, immunotherapy for oncologic disease, Covid-19, and vaccines) defined as those newly identified risk factors. Accurate patient information and monitoring of risk factors as well as planned follow-ups may help to prevent and treat the worsening of psoriasis and consequently improve the quality of life of psoriatic patients.

Unaddressed Challenges in the Treatment of Cutaneous Melanoma?

Background and Objectives: While the management of noninvasive cutaneous melanoma (CM) is typically limited to a secondary excision to reduce recurrence risk and periodic follow-up, treating patients with advanced melanoma presents ongoing challenges. Materials and Methods: This review provides a comprehensive examination of both established and emerging pharmacologic strategies for advanced CM management, offering an up-to-date insight into the current therapeutic milieu. The dynamic landscape of advanced CM treatment is explored, highlighting the efficacy of immune checkpoint inhibitors and targeted therapies, either in monotherapy or combination regimens. Additionally, ongoing investigations into novel treatment modalities are thoroughly discussed, reflecting the evolving nature of melanoma management. Results: The therapeutic landscape for melanoma management is undergoing significant transformation. Although various treatment modalities exist, there remains a critical need for novel therapies, particularly for certain stages of melanoma or cases resistant to current options. Conclusions: Consequently, further studies are warranted to identify new treatment avenues and optimize the utilization of existing drugs.

Long-Term Efficacy and Safety of Guselkumab in Psoriasis Patients Who Failed Anti-IL17: A Two-Year Real-Life Study.

Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of interleukin (IL)-23. Despite its effectiveness and safety, which have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 are limited or characterized by a reduced follow-up period. These data are essential to guide clinicians in biologic switching, considering that anti-IL23 and anti-IL17 partially share their therapeutic targets, as well as some patients who may have to interrupt treatment with anti-IL17 for loss of efficacy over time or the development of adverse events (AEs). In this context, we performed a retrospective study with the aim of evaluating the long-term use (2 years) of guselkumab in psoriasis patients who previously failed at least one anti-IL17 in a real-life setting, also focusing attention on psoriasis located in difficult-to-treat areas (the scalp, palms or soles, fingernails, genitals). A total of 61 patients (35 male, 57.4%; mean age 57.6 ± 8.8 years) were enrolled. Of these, 30 (49.2%) patients failed secukinumab, 21 (34.4%) failed ixekizumab, 7 (11.5%) failed brodalumab, and 3 (4.9%) failed both secukinumab and ixekizumab. At the baseline, the mean PASI and BSA were 12.8 ± 8.4 and 24.5 ± 26.6, respectively. During week 16, PASI90 and PASI100 responses were achieved by 60.7% and 37.7% of patients, respectively, which continued to improve up to week 104 (PASI90: 73.8%, PASI100: 59.0%). Clinical improvement in difficult-to-treat areas was detected as well. In particular, a slower improvement for fingernails and the palmoplantar region was reported compared to scalp and genital psoriasis at week 16. However, no differences were found following 28 weeks of therapy. Primary and secondary inefficacy were reported by 1 (1.6%) and 5 (8.2%) patients. As regards safety, no severe AEs were collected.

Effectiveness and Safety of Tildrakizumab in Psoriasis Patients Who Failed Anti-IL17 Treatment: A 28-Week Real-Life Study.

Tildrakizumab is a humanised IgG1/k-type monoclonal antibody that targets the p19 protein subunit of IL23. Despite its effectiveness and safety have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 (brodalumab, ixekizumab, bimekizumab and/or secukinumab) are scant. Therefore, further studies on this topic would be beneficial for clinicians in guiding the selection of biologic shifting, considering that anti-IL23, -12/23, and -IL17 partially share their therapeutic targets. In this context, we performed a 28-week, single-center, real-life, retrospective study, with the aim of assessing the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17, also focusing the attention on psoriasis located in difficult-to-treat areas (scalp, palms or soles, fingernails, genitals). A total of 23 patients (12 male, 52.2%; mean age 52.8 ± 12.4 years) were enrolled. Of these, 11 (47.8%) failed secukinumab, 7 (30.4%) ixekizumab, 3 (13.0%) brodalumab, 1 (4.3%) both secukinumab and ixekizumab and 1 (4.3%) bimekizumab. At baseline, mean PASI and BSA were 12.8 ± 5.9 and 18.7 ± 9.6, respectively. At W16 PASI75 and PASI90 response were achieved by 15 (65.2%), and 9 (39.1%) patients, respectively, whereas 19 (82.6%) and 13 (56.6%) subjects reached these scores at W28. One (4.3%) case of primary inefficacy and 1 (4.3%) case of secondary inefficacy were assessed. Finally, no severe adverse events were collected. Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not directly affect its effectiveness.

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.

Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation.

Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients' comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer.

Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis.

Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. In the attempt to molecularly classify 17 unrelated Italian patients referred with congenital nonsyndromic ichthyosis, we performed massively parallel sequencing of over 50 ichthyosis-related genes. Genetic data of 300 Italian unaffected subjects were also analyzed to evaluate frequencies of putative disease-causing alleles in our population. For all patients, we identified the molecular cause of the disease. Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations. Three patients had biallelic loss-of-function variants in FLG, whereas 6/11 males were affected by X-linked ichthyosis. Among the 24 different disease-causing alleles we identified, 8 carried novel variants, including a synonymous TGM1 variant that resulted in a splicing defect. Moreover, we generated a priority list of the ichthyosis-related genes that showed a significant number of rare and novel variants in our population. In conclusion, our comprehensive molecular analysis resulted in an effective first-tier test for the early classification of ichthyosis patients. It also expands the genetic, mutational, and phenotypic spectra of inherited ichthyosis and provides new insight into the current understanding of etiologies and epidemiology of this group of rare disorders.

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.

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.

Efficacy and Safety of bimekizumab in psoriasis management in real-life: bio-naïve vs bio-experienced.

Bimekizumab is the latest monoclonal antibody approved for the management of moderate-to-severe plaque psoriasis. Currently, data investigating its use in real-life setting are limited. Therefore, we performed a short term [(16 weeks (W)] real-life, monocentric, prospective study aiming to assess the efficacy and safety of bimekizumab, also comparing bio-naïve vs bio-experienced patients. Globally, 56 patients were included. At baseline, mean PASI and DLQI were 16.9±7.8 and 22.6±5.9, respectively. PASI75/90/100 were reached by 76.8%/50.0%/42.9% of patients at W4 and by 92.9%/82.1%/69.6% of subjects at W16. In our cohort, 29 (51.8%) patients were bio-naïve whereas 27 (48.2%) bio-experienced. At baseline, both PASI and DLQI were significantly higher in bio-naïve cohort as compared with bio-experienced group (PASI: 19.4±7.7 vs 14.2±7.0, p<0.05; DLQI: 25.3±4.5 vs 19.7±6.0, p<0.001). Despite not significant, a higher percentage of patients in bio-naïve cohort as compared with bio-experienced group reached PASI75 (79.3% vs 63.0%, p=0.176), PASI90 (62.1% vs 44.4%, p=0.186) and PASI100 (48.3% vs 37.0%, p=0.396) at W4. However, the percentage of PASI75/90/100 response were similar between the two cohorts at W16. Regarding safety, 3 candidiasis (5.4%) and 1 (1.8%) eczematous reaction were reported, without differences between the two groups. Finally, 2 (3.6%) bimekizumab discontinuation for treatment failure and 3 (5.4%) for AEs were collected.

Biological Therapy for Psoriasis in Cancer Patients: An 8-Year Retrospective Real-Life Study.

Background: It is now recognized that psoriasis plays a key role in the development of several comorbidities, such as cardiovascular disease, and metabolic syndrome. Some authors have hypothesized that patients with psoriasis may have an increased risk of developing certain types of cancer. The efficacy and safety of biologic drugs are well-documented in clinical trials and in real-life studies. However, there is limited evidence on the safety of the use of biologic treatments in cancer patients with psoriasis, and the use of this therapeutic class in patients with a pre-existing or concomitant malignancy is still debated. Methods: We have conducted a retrospective observational study of a group of oncology patients with moderate-to-severe psoriasis treated with biologic therapy at the Dermatology Clinic of the University of Naples Federico II, during the period from 2016 to 2024. We included 20 adult patients; in 15 of them the diagnosis of neoplasm preceded the start of treatment biologic, while four of these patients had been diagnosed with cancer during the course of therapy biologics. Results: The most represented neoplasms in our population were breast carcinoma, prostate carcinoma, thyroid carcinoma, and chronic lymphatic leukemia. Anti-IL17 drugs were the most frequently prescribed (47.7%), followed by anti-IL23p19 (36.8%), anti-IL-12/23 (10.5%) and anti-TNF alpha (5.26%). All patients showed improvement of psoriasis after starting the therapy. Conclusions: Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.