Short-term efficacy of tildrakizumab on difficult-to-treat areas: a real-world experience.

BACKGROUND: Novel biologics targeting the IL23/T-17 axis, such as tildrakizumab, have been developed to treat psoriasis. There is limited evidence on the use of tildrakizumab for the treatment of psoriasis in difficult-to-treat areas. OBJECTIVE: Our aim was to evaluate the short-term efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis and with the involvement of difficult-to-treat areas. METHODS: A multicentric retrospective study was conducted on patients who initiated tildrakizumab between July 2022 and July 2023. Psoriasis Area and Severity Index (PASI), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Area and Severity Index (ppPASI), and Nail Psoriasis Severity Index (NAPSI) were measured at baseline and after 16 weeks. The percentages of achieving a PASI75, PASI90, or PASI100 response were assessed. Dermatology Life Quality Index (DLQI) and Itch Visual Analog Scale (VAS) were measured simultaneously. Data about potential safety issues and adverse events were collected. RESULTS: A total of 76 patients were included, and 59 (77.6%) were affected by psoriasis localized to the scalp (n = 32), palmoplantar locations (n = 13), or nails (n = 14). The mean PASI score decreased from 16.5 ± 9.8 at baseline to 1.9 ± 1.6 after 16 weeks. Tildrakizumab treatment resulted in the improvement of PSSI (19.9 ± 10.7 to 2.7 ± 4.2), ppPASI (15.4 ± 6.9 to 1.9 ± 2.3), and NAPSI (20.3 ± 16.9 to 7.6 ± 10.8) from baseline to 16 weeks, respectively. DLQI and Itch VAS also showed marked improvement. CONCLUSIONS: Tildrakizumab is a valuable option for treating difficult-to-treat psoriasis and pruritus, with rapid onset of action.

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.

Drug-induced photosensitivity associated with anticancer therapies.

INTRODUCTION: Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event. EVIDENCE ACQUISITION: A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. EVIDENCE SYNTHESIS: A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies. CONCLUSIONS: Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.

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.

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.

Effectiveness and safety of risankizumab in VEry severe plaque psoriasis: a real-life retrospective study (VESPA-Study).

BACKGROUND: The recent introduction of biological drugs specifically targeting the interleukins involved in psoriasis pathogenesis revolutionized the therapeutic scenario of moderate to severe forms of psoriasis. Among these, risankizumab, an anti-IL-23, was shown to be effective both in clinical trials and real-life experiences. However, data on its use on very severe forms of psoriasis, defined by a Psoriasis Area Severity Index (PASI) of at least 30, are scant. In this context, our study aimed to investigate the outcomes of patients with very severe psoriasis, and the involvement of difficult-to-treat areas treated with risankizumab for up to 2 years. METHODS: A retrospective, observational study enrolled patients with very severe plaque psoriasis and the involvement of difficult-to-treat areas undergoing treatment with risankizumab. Clinical and demographic data were collected at baseline. Moreover, at baseline and each dermatological examination (16, 28, 40 and 104 weeks), clinical improvement was measured using the percentage of patients achieving PASI 75/90/100 response, site-specific Psoriasis Global Assessment and Dermatology Life Quality Index. RESULTS: At baseline, the mean PASI was 35.1 ± 5.1. A significant reduction was observed since week 16 and maintained up to week 104. Moreover, the Psoriasis Global Assessment and Dermatology Life Quality Index improved as well. CONCLUSIONS: Risankizumab showed to be effective and safe in patients affected by very severe forms of psoriasis with the involvement of difficult-to-treat areas.

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.

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.

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.

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 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.

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.

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.