Traditional Systemic Treatments Research Articles

Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China.

Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with COVID-19-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Among the infected group, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR]=8.197, 95% confidence interval [95% CI]=5.685-11.820, compared to no lesions), hypertension (adjusted OR=1.582, 95% CI=1.068-2.343), traditional systemic (adjusted OR=1.887, 95% CI=1.263-2.818), and nonsystemic treatment (adjusted OR=1.602, 95% CI=1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR=0.931, 95% CI=0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. ClinicalTrials.gov (No. NCT05961605).

Overcoming Resistance in Prostate Cancer Therapy Using a DZ-Simvastatin Conjugate.

Prostate cancer (PC), particularly its metastatic castration-resistant form (mCRPC), is a leading cause of cancer-related deaths among men in the Western world. Traditional systemic treatments, including hormonal therapy and chemotherapy, offer limited effectiveness due to tumors' inherent resistance to these therapies. Moreover, they often come with significant side effects. We have developed a delivery method using a tumor-cell-specific heptamethine carbocyanine dye (DZ) designed to transport therapeutic agents directly to tumor cells. This research evaluated simvastatin (SIM) as the antitumor payload because of its demonstrated chemopreventive effects on human cancers and its well-documented safety profile. We designed and synthesized a DZ-SIM conjugate for tumor cell targeting. PC cell lines and xenograft tumor models were used to assess tumor-cell targeting specificity and killing activity and to investigate the corresponding mechanisms. DZ-SIM treatment effectively killed PC cells regardless of their androgen receptor status or inherent therapeutic resistance. The conjugate targeted and suppressed xenograft tumor formation without harming normal cells of the host. In cancer cells, DZ-SIM was enriched in subcellular organelles, including mitochondria, where the conjugate formed adducts with multiple proteins and caused the loss of transmembrane potential, promoting cell death. The DZ-SIM specifically targets PC cells and their mitochondria, resulting in a loss of mitochondrial function and cell death. With a unique subcellular targeting strategy, the conjugate holds the potential to outperform existing chemotherapeutic drugs. It presents a novel strategy to circumvent therapeutic resistance, offering a more potent treatment for mCRPC.

Current and Emerging Therapies for Atopic Dermatitis in the Elderly.

Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis andpathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.

Efficacy and safety of biologics and small molecules for psoriasis in pediatric and geriatric populations. Part II: focus on elderly patients

Introduction The management of moderate-to-severe forms of psoriasis is becoming a frequent concern in geriatric age due to the higher risk to develop treatment adverse events, logistic issues, vulnerability to immune-related diseases and cancer, presence of comorbidities and the risk of drug interactions. In this context, traditional systemic treatments are often contraindicated, and biologic drugs and small molecules seem to be a valuable option. However, data on their effectiveness and safety in elderly patients are scant. Areas covered The aim of this review is to analyze the current literature in order to point out data on the efficacy and safety of biologic drugs and small molecules for the management of psoriasis in elderly patients in order to put the basis for universally shared treatment algorithm following available evidence. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used for the literature research. Expert Opinion/Commentary Our review suggests biologics and small molecules as an effective and safe option for the management of moderate-to-severe forms of psoriasis in elderly patients.

Traditional Systemic Treatment Options in Advanced Low-Grade Serous Ovarian Cancer after Successful Cytoreduction: A Systematic Review and Meta-Analysis.

Simple SummaryLow-Grade Serous Ovarian cancer (LGSOC) is considered less sensitive to traditional chemotherapy than its high-grade counterpart. Guidelines are still inconsistent around the use and value of cytotoxic and antihormonal agents in the adjuvant setting. Traditional cytotoxic or antihormonal systemic treatment option is not associated with a significant OS or PFS benefit in this Meta-analysis.Objective: We performed a systematic literature review and a subsequent meta-analysis to compare traditional treatment options, i.e., antihormonal and cytotoxic, in LGSOC. Methods: We conducted a systematic literature review in MEDBASE and MEDLINE between September 2000 and June 2021 for women who received cytotoxic chemotherapy and/or antihormonal treatment after primary cytoreduction due to stage II–IV LGSOC and also at relapse. PFS and OS were calculated depending on the type of their adjuvant treatment. For each endpoint in the meta-analysis, pooled HR was calculated using the random effect model with the inverse variance weighted method. Only primary patients were included in the subsequent meta-analysis due to the small number of studies in the relapsed setting. Results: Five eligible first-line studies were included. Systemic chemotherapy failed to provide a significant OS benefit when compared to no systemic treatment (pooled HR = 1.01, 95% CI [0.79, 1.29]) after successful cytoreduction. Moreover, systemic chemotherapy followed by antihormonal treatment also did not result to a significant PFS or OS benefit when compared to systemic chemotherapy alone (for PSF: pooled HR = 0.59, 95% CI [0.33, 1.04]; for OS: pooled HR = 0.83, 95% CI [0.50, 1.39]). There were insufficient data from studies in the recurrent setting to allow their inclusion in the meta-analysis. Conclusions: In this meta-analysis, we failed to identify a traditional cytotoxic or antihormonal systemic treatment option that was associated with a significant OS or PFS benefit when administered following successful cytoreduction for advanced LGSOC. Prospective randomized studies are urgently warranted to define optimal adjuvant options in this challenging disease.

STING Signaling and Skin Cancers.

Simple SummaryStimulator of interferon genes (STING) is currently recognized as a driver for anti-tumor immunity against various malignancies and is expected to enhance the anti-tumor effects. In this review, we summarized recent knowledges gained from epigenetics-mediated skin cancer development and discussed the clinical application of STING agonists in the treatment of skin cancer.Recent developments in immunotherapy against malignancies overcome the disadvantages of traditional systemic treatments; however, this immune checkpoint treatment is not perfect and cannot obtain a satisfactory clinical outcome in all cases. Therefore, an additional therapeutic option for malignancy is needed in oncology. Stimulator of interferon genes (STING) has recently been highlighted as a strong type I interferon driver and shows anti-tumor immunity against various malignancies. STING-targeted anti-tumor immunotherapy is expected to enhance the anti-tumor effects and clinical outcomes of immunotherapy against malignancies. In this review, we focus on recent advancements in the knowledge gained from research on STING signaling in skin cancers. In addition to the limitations of STING-targeted immunotherapy, we also discuss the clinical application of STING agonists in the treatment of skin cancer.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy.MethodsThe annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%).ResultsThe most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 – €39,280) and ixekizumab (range: €11,092 – €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60–80%), which was achieved early in time.ConclusionBiologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

694P Methylthioadenosine phosphorylase (MTAP) deletion is more common in sarcomatoid (srcRCC) than in clear cell renal cell carcinoma (ccRCC)

srcRCC is an aggressive variant of RCC that frequently presents as advanced-stage disease refractory to traditional systemic treatments for ccRCC. Emerging potential treatment strategies for metastatic srcRCC include immune checkpoint inhibitors (ICPIs) and novel synthetic lethality agents that exploit the genomic loss of MTAP.

An Association of Pediatric Psoriasis with Metabolic Syndrome in Thai Children: 20 Years Retrospective Study.

PurposeTo explore epidemiological data of pediatric psoriasis age under 18 years old regarding, types of psoriasis, the correlation with metabolic syndrome (MetS), treatments, and treatment outcomes of at least one year follow-up.Patients and MethodsThis was a 20-year-retrospective study of pediatric psoriasis patients in a single tertiary pediatric referral center, Faculty of Medicine, Khon Kaen University, Thailand, between January 2001 and December 2020. The diagnosis of psoriasis was based on recorded diagnosis from ICD-10, and medical record was evaluated by certified pediatricians.ResultsThere were 177 pediatric psoriasis in the study population. The mean age was 10.50, SD 4.80. The mean body mass index (BMI) was 19.10 (SD 5.44). There were 52 cases (29.37%) with MetS. Pediatric psoriasis patients over the age of 12 years old developed MetS 27 out of 70 cases (0.38) compared to the patients younger than 12 years old (25 out of 107 cases, 0.23), absolute risk reduction = 0.15, 95% CI 0.01–0.29, P = 0.029. The overall outcomes of pediatric psoriasis were good even though traditional topical and systemic treatments were provided in the study population.ConclusionThe present study revealed that there was 15% increased MetS in the pediatric psoriasis patients over the age of 12 years old as compared to the patients of prepubertal age (≤12 years old). Increased attention to the early detection of MetS in pediatric psoriasis is recommended. Biologic therapy would be an alternative option in severe recalcitrant pediatric psoriasis cases in the future.

New Biologics for the Treatment of Atopic Dermatitis: Analysis of Efficacy, Safety, and Paradoxical Atopic Dermatitis Acceleration

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.

PD-L1 expression in sebaceous carcinomas.

Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option. A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning. A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases. Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.

New emergent therapies for atopic dermatitis: A review of safety profile with respect to female fertility, pregnancy, and breastfeeding.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Systemic treatment is usually mandatory in moderate-to-severe AD of the adult; these patients need to be informed about safe and effective management of AD also regarding the reproduction. Treating a pregnant woman with AD with systemic drugs may affect the unborn child. While effects of traditional systemic treatments for AD on female fertility, pregnancy, and breastfeeding are largely known, data about new emergent therapies for AD are still poor. Treating pregnant or lactating women with AD can be a challenge since no large clinical studies on its possible effects and side-effects on conception, pregnancy, the unborn child and lactation are currently available for new AD treatments.

Mechanism-based treatment of cancer with immune checkpoint inhibitor therapies.

Immune checkpoints are cell surface molecules that initiate regulatory pathways which have powerful control of CD8+ cytolytic T cell activity. Antagonistic and agonistic antibodies engaging these molecules have demonstrated profound impact on immune activation and have entered clinical use for the treatment of a variety of diseases. Over the past decade, antagonistic antibodies known as immune checkpoint inhibitors have become a new pillar of cancer treatment and have reshaped the therapeutic landscape in oncology. These agents differ in their mechanism of action and toxicity profiles compared to more traditional systemic cancer treatments such as chemo- and targeted therapies. This article reviews the pharmacology of this new class of agents.

Guidelines for the Diagnosis and Treatment of Psoriasis in China: 2019 Concise Edition#

Abstract Psoriasis is an immune-mediated chronic, recurrent, systemic inflammatory disease induced by the combination of hereditary and environmental factors. The etiology of psoriasis involves hereditary, immune, environmental, and other factors, and its pathogenesis is considered to involve excessive proliferation of keratinocytes or inflammatory activation of synovial cells and chondrocytes within joints; these processes are caused by an immune response that is mainly mediated by T lymphocytes and various other immune cells. Psoriasis is an incurable disease, and the goal of treatment is to control the progression of disease and maintain long-term efficacy. Treatment protocols should be based on the patients’ conditions. Patients with mild psoriasis can be mainly treated with topical agents, and those with moderate to severe psoriasis can be treated with systemic medications. Targeted biological agents can be appropriately chosen for cases of psoriasis that are resistant to traditional systemic treatment. New drugs and treatments for psoriasis continue to evolve and emerge, and our updated guidelines are designed to deliver new achievements from China and to physicians worldwide and to keep pace with global progress on psoriasis research. Compared with the previous two editions, part of contents have been modified and revised in the present guidelines; this will further facilitate standardization and increase the efficiency of the diagnosis and treatment of psoriasis in China, and improve patients’ quality of life.

Mathematical Prostate Cancer Evolution: Effect of Immunotherapy Based on Controlled Vaccination Strategy.

Basic immunology research over several decades has led to an improved understanding of tumour recognition by components of the immune system and mechanism of tumour evasion from immune detection. These findings have ultimately led to creating antitumour immunotherapies in patients with different kind of cancer including prostate cancer. The increasing number of reports confirms that immune-based therapies have clinical benefit in patients with prostate cancer with potentially less toxicity in comparison with traditional systemic treatments including surgical resection, chemotherapy, or radiotherapy in various forms. This review focuses on the possibility of modulation of the optimal immunotherapy based on vaccination strategy adopted to individual patients in order to increase quality and quantity of their life.

Rosai-Dorfman病的治疗新进展

Rosai-Dorfman disease (RDD) , also known as sinus histiocytosis with massive lymphadenopathy, is a rare benign self-limited histiocytic proliferative disorder with undetermined etiology. There is still no specific treatment for RDD. Surgical excision is the first-line treatment, while topical and systemic therapy can be chosen for the patients who are not unfit for surgery. Classic topical therapies include topical treatment or local injection with glucocorticoids. Photodynamic therapy and laser immunotherapy are considered as promising topical treatments. Traditional systemic treatments include oral glucocorticoids, immunomodulators, acitretin, and so on. Rituximab is a new treatment option for patients with CD20-positive RDD. This review summarizes new progress in the treatment of RDD in recent years. Key words: Histiocytosis, sinus; Therapy; Surgical procedures, operative; Drug therapy; Sinus histiocytosis with massive lymphadenopathy

Patient and physician preferences for atopic dermatitis injection treatments in Japan

Background: Recently, biologic agents administered as a subcutaneous injection have been introduced as treatment options for atopic dermatitis (AD). Biologic treatments differ considerably from traditional topical and systemic anti-inflammatory treatments, and it is unclear how this may impact patient and physician preferences for treatments.Objective: To examine the treatment preferences for new injection treatments of patients and physicians.Methods: Discrete choice experiment methodology was used to quantify preferences for treatments via an online survey. Participants were presented with a series of choice scenarios; treatment options were described using the following attributes: add-on or replacement treatment, efficacy of improving rashes and itching, time until response, place of administration, injection site reaction, risk of mild-to-moderate and severe side effects, frequency of administration and cost.Results: 76.67% of physicians and 46.24% of patients opted-in to the new treatment in the scenarios presented. Of those who opted-in to treatment, physicians were more likely to value the efficacy of treating rashes and were more concerned about cost than patients. Patients preferred add-on treatments and were against self-administering the treatment at home.Conclusion: Overall patients and physicians differ in their preferences for AD treatments. These findings have implications for shared decision making and clinical practice.

Treatment response in patients with moderate-to-severe psoriasis who had inadequate response to prior secukinumab

Background/Objective: Secukinumab is an effective treatment for psoriasis, and it has been reported to be effective in patients who failed on multiple prior biologics. However, treatment failure of secukinumab is possible and the alternative management in these patients remains poorly studied. Methods: We reviewed the treatment efficacy of all patients with moderate-to-severe psoriasis who used secukinumab as monotherapy and did not reach Psoriasis Area Severity Index 75 (PASI 75) response at week 16 (primary failure) or later (secondary failure). The treatment response of these patients during subsequent treatments was recorded. Optimal PASI improvement between weeks 12 and 20 and at the end of observation period was recorded. Results: Traditional systemic treatment (n = 4), etanercept (n = 1), adalimumab (n = 6), secukinumab weekly reloading (n = 2), or ustekinumab (n = 4) was administered in 16 patients (one with both ustekinumab and adalimumab). Six patients reached PASI 75 at week 16, including three (50%) with adalimumab. PASI 75 response was maintained in four patients at the end of observation period. Two (50%) of them used adalimumab, one used methotrexate plus acitretin, and the other used secukinumab. Conclusion: Adalimumab demonstrates better response in patients with refractory psoriasis to secukinumab. Traditional systemic medication and re-loading of secukinumab can also provide some benefits.

Secondary failure of TNF-α inhibitors in clinical practice.

Tumor necrosis factor alpha (TNF-α) is a leading inflammatory cytokine that plays a pivotal role in the pathogenesis of psoriasis. In case of a severe course of psoriasis and moderate-to-severe disease in which traditional systemic treatments are ineffective or contraindicated, TNF-α inhibitors (iTNF-α) are used. This class of drugs includes monoclonal antibodies and a fusion protein (etanercept) and can induce a humoral or cell-mediated immune response, leading to formation of anti-drug antibodies (ADAs). The immunogenicity may affect iTNF-α drug pharmacokinetics, which would lead to hampering the clinical response (secondary drug failure), so a need to increase the drug dose arises. Antibodies against monoclonal antibodies (adalimumab, infliximab) have been associated with diminished clinical response, while against etanercept are non-neutralizing and appear to have no significant effect on clinical response and treatment safety. Switching of biologic agents may be one strategy in ADA-associated secondary failure of iTNF-α. However researches are needed to identify risk factors for ADA development and investigate management strategies for optimized treatment response. The authors reviewed the literature on the effectiveness of iTNF-α and pointed out the prevention of secondary failure in clinical practice.

A psoriasis hagyományos szisztémás kezelése

A psoriasis hagyományos szisztémás kezelése