Treatment Of Psoriasis Research Articles

The Intersection of Psoriasis and Neoplasia: Risk Factors, Therapeutic Approaches, and Management Strategies

The association between psoriasis and increased cancer risk is gaining recognition as studies reveal shared inflammatory and immune pathways. This review examines the relationship between psoriasis and neoplasia, focusing on cancer risk factors in psoriasis patients, the biological pathways underlying this connection, and the impact of various psoriasis treatments on cancer development. Psoriasis patients have a heightened incidence of certain cancers, such as lymphomas, skin cancers, and urological malignancies, potentially linked to immune dysregulation and chronic inflammation. Immunomodulatory treatments for psoriasis, including conventional systemic therapies and biologics, present varied cancer risks, with others, such as phototherapy, associated with an elevated risk of skin cancers. For oncologic patients with psoriasis, management necessitates a tailored approach, balancing effective psoriasis control with minimizing cancer progression risks. The emergence of IL-17 inhibitors, IL-23 inhibitors, and small-molecule therapies offers promising therapeutic alternatives with favorable safety profiles for these patients. This review underscores the need for interdisciplinary collaboration to optimize care for patients managing both psoriasis and malignancy.

Patients’ Acceptance of Psoriasis Depends on Disease Severity, Itch Intensity, and the Patients’ Quality of Life: A Cross-Sectional Study

Background/Objectives: Psoriasis is a chronic skin disorder affecting over 60 million people worldwide, with both physical and psychological impacts due to the visible lesions and associated somatic symptoms. This study aimed to assess disease acceptance among psoriasis patients and to explore its correlation with disease severity, itch intensity, and quality of life (QoL) Methods: The study included 166 psoriasis patients, comprising 101 men and 65 women, all with a disease duration of at least one year. Clinical and psychological aspects of psoriasis were comprehensively assessed using various standardized tools, along with a demographic questionnaire. Results: The study found that psoriasis patients had a mean illness acceptance score of 25.1 points, with most respondents (44%) exhibiting a moderate level of acceptance. A high level of acceptance was observed in 28% of participants, while an equal proportion of patients (28%) demonstrating low acceptance, with no significant gender-based differences. Acceptance was negatively correlated with disease severity (PASI score), quality of life impairment (DLQI), and itch intensity (NRS), indicating that lower acceptance was linked to more severe symptoms. Additionally, a slight negative correlation was observed between acceptance and disease duration, while acceptance levels were unaffected by factors such as education, relationship status, or age of disease onset. Conclusions: A comprehensive approach to psoriasis treatment should address not only the physical aspects but also the psychological challenges faced by patients, with a particular focus on improving disease acceptance as a coping strategy. Reducing itch intensity may contribute to better disease acceptance.

Limonin Exhibits Anti-Inflammatory Effects by Inhibiting mTORC1 and Mitochondrial Reactive Oxygen Species in Psoriatic-like Skin Inflammation

Psoriasis is a chronic inflammatory skin disorder characterized by abnormal immune responses and keratinocyte hyperproliferation. Limonin, a bioactive compound found in citrus fruits, has anti-inflammatory properties in various models; however, its effects on psoriasis are not fully understood. We investigated the therapeutic potential of limonin in a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis mouse model. Mice were treated with TPA to induce psoriasis-like skin lesions, followed by intraperitoneal administration of limonin (200 or 400 μg/mouse) for six days. The results showed that limonin improved psoriasis-related symptoms in a psoriasis-like mouse model by suppressing the mRNA expression of pro-inflammatory cytokines and inflammation-related antimicrobial peptides and regulating the expansion of myeloid cells and T cells. Specifically, limonin reduced glucose uptake and oxidative phosphorylation to shift the metabolic program in the inflamed skin cells of psoriasis-like mice. Limonin activates AMPK and proteins related to mTOR inhibition, thereby suppressing the mTOR signaling pathway. It also inhibits mitochondrial mass and mitochondrial ROS production, thereby preventing the development of dysfunctional mitochondria in inflamed skin cells. Overall, limonin modulates key immune responses and metabolic pathways related to inflammation and mitochondrial health in psoriasis. Therefore, it is a promising natural candidate for the treatment of psoriasis and various inflammatory skin diseases.

A narrative review of thalassotherapy and the health benefits of seawater and coastal climates.

Thalassotherapy refers to the therapeutic use of controlled exposure to marine environments and their natural elements for health promotion. This review aims to summarize evidence-based clinical applications of thalassotherapy. A narrative review was conducted, with PubMed searched in September 2024 for clinical studies evaluating the efficacy of thalassotherapy. Relevant evidence was summarized and critically analyzed. A total of 566 articles were identified, of which 16 studies met the inclusion criteria. Thalassotherapy was primarily studied for its effects on skin disorders, including psoriasis, atopic dermatitis, and vitiligo, as well as rheumatic conditions like fibromyalgia and ankylosing spondylitis. The intervention showed significant improvements in disease severity and patient quality of life, with the strongest evidence seen in psoriasis and fibromyalgia treatment. Thalassotherapy appears beneficial for symptom relief in several conditions, particularly skin and rheumatic disorders. However, further research is needed to quantify its effect size, evaluate long-term benefits, assess potential risks, and identify factors that may influence treatment outcomes.

Psoriasis and oncology: is there a way out?

In severe psoriasis, systemic therapy is required, but the number of studies on the use of biologics drugs in patients with existing or history of cancer is limited, which creates difficulties in prescribing this group of drugs. The presented clinical case demonstrates the interdisciplinary interaction between a dermatologist and an oncologic surgeon. A patient diagnosed with psoriasis, psoriatic arthritis, and basal cell carcinoma underwent successful therapy with the IL-23 inhibitor risankizumab, which has demonstrated high safety and efficacy in the treatment of psoriasis, and surgical removal of the basal cell carcinoma by Mohs micrographic surgery. For patients with psoriasis and an existing or history of cancer, multidisciplinary collaboration is required to determine optimal therapeutic tactics.

P91 Bimekizumab-induced drug reaction with eosinophilia and systemic symptoms syndrome

Abstract Drug reaction with eosinophilia and systemic symptoms syndrome (DRESSs) is a potentially life-threatening drug-induced reaction which can present with cutaneous, haematological and internal organ involvement. It is a T-cell-mediated delayed-type drug hypersensitivity reaction and although the pathogenesis is not yet fully understood, it has been recognized also to have significant genetic associations. Bimekizumab is the first monoclonal antibody to selectively inhibit IL-17F and IL-17A and has been approved for the management of plaque psoriasis and psoriatic arthritis in the UK and EU. We present a case of Bimekizumab-induced DRESS syndrome which, to our knowledge, has not yet been described in the literature. The patient is a 45-year-old male with chronic plaque psoriasis who presented with fevers, tachycardia, erythroderma, generalized oedema and lymphadenopathy 10 days after his first treatment with Bimekizumab. He had previously been established on Adalimumab but was still experiencing persistent flares of psoriasis. Laboratory results revealed eosinophilia, raised inflammatory markers and deranged liver function. Histology showed patchy interface dermatitis and moderate-to-severe perivascular chronic inflammatory infiltrate in the dermis with numerous eosinophils, but no psoriasiform changes. He fulfilled the diagnostic criteria for DRESSs, prompting discontinuation of Bimekizumab, treatment with fluid resuscitation, topical steroids and emollients. This resulted in an improvement in clinical picture and laboratory results over a 4-day hospital admission. However, upon tapering down the topical steroids, there was a worsening of his cutaneous symptoms. He developed a generalized eczematous rash on the trunk and limbs with acral oedema. This was further managed with oral ciclosporin and topical steroids. However, upon tapering down the topical steroids, there was worsening of his cutaneous symptoms. He developed a generalised erythematous scaly rash on trunk and limbs with acral oedema. This was further managed with oral ciclosporin and topical steroids. He was subsequently started on Rinsakizumab for the management of his psoriasis. This is a novel case report which demonstrates DRESSs in the context of Bimekizumab treatment for chronic plaque psoriasis. Generally, symptoms develop following a latency period of 3–8 weeks although studies have described ‘rapid-onset DRESSs’ which occurs <15 days following initiation of the culprit drug, which have primarily included antibiotics and contrast media. In this case, the onset of symptoms was earlier than is typically seen in DRESSs and the case highlights the importance of considering this established biologic as a potential cause of DRESSs in future cases.

P42 KLHDC7B participates in the mechanism of UVB treatment for psoriasis by regulating CHOP and the KEAP1/NRF2 pathway

Abstract Objective UVB phototherapy is an important method for the treatment of psoriasis, but the specific mechanism is unclear. KLHDC7B is a Kelch domain-containing protein that has been widely noted involving in multiple important cellular processes, but its expression and function in psoriasis remain to be further elucidated. The objective of this study was to explore the levels of KLHDC7B in psoriasis lesions and psoriasis keratinocytes with UVB irradiation. In addition, this study aimed to investigate whether KLHDC7B participates in the UVB treatment in patients with psoriasis. Methods We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting to determine the levels of KLHDC7B. QRT-PCR and ELISA were used to detect the secretion levels of IL-1β, CCL20 and CXCL10. Cell apoptosis was analysed by flow cytometric method. QRT-PCR and Western blotting were used to detect the expression of CHOP and KEAP1/NRF2 pathway. The results were statistically analysed by t-test. Results Our study showed a high expression of KLHDC7B in psoriasis lesions and keratinocytes stimulated with M5 for the psoriasis model. After UVB treatment, KLHDC7B was further increased. Knockdown of KLHDC7B reversed UVB-induced apoptosis and levels of IL-1β, CCL20 and CXCL10. Overexpression of KLHDC7B can improve the endoplasmic reticulum stress marker protein CHOP expression and NRF2 level. KLHDC7B could induce CHOP-mediated apoptosis and activate the KEAP1/NRF2 pathway to alleviate inflammation. In addition, we found that UVB promoted KLHDC7B expression through the nearby LncRNA called LncKLHDC7B-2. Conclusion KLHDC7B may act as a disease suppressor and play a key role in UVB treatment for psoriasis, which may provide a new target for treatment.

P48 Maintenance response of guselkumab in the Chinese population: an interim analysis of an observational study

Abstract Maintenance treatment with biologics is recommended for the treatment of moderate-to-severe psoriasis; however, treatment withdrawal occurs frequently in the real world. In a post-approval commitment (PAC) study (NCT04914429), guselkumab demonstrated efficacy in Chinese patients with moderate-to-severe plaque psoriasis. Here, we report interim analysis results from the observational post-PAC study evaluating health-related quality of life (HRQoL) and psoriasis relapse within 24 weeks following guselkumab withdrawal. This prospective, observational study enrolled patients who achieved a psoriasis area and severity index (PASI) 75 response at Week 44 in the PAC study. In the framework of a decentralized clinical trial design, patients utilized an electronic patient-reported outcome system to report on HRQoL, psoriasis status, and administration of systemic treatment for psoriasis. HRQoL was assessed by the dermatology life quality index (DLQI) at baseline, then every 12 weeks through Week 48. Psoriasis relapse was defined as the initiation of a new systemic treatment for psoriasis. Off-treatment duration (OTD) was defined as the time between the last guselkumab administration at Week 44 in the PAC study and the date of the first dose of any systemic treatment for psoriasis, loss to follow-up, death, or end of the study. A planned interim analysis was conducted when all patients had completed questionnaires 24 weeks after guselkumab withdrawal. The data cut-off (DCO) date was 3 June 2024. A total of 243 patients were enrolled. As of DCO, two patients withdrew from the study due to loss of follow-up. Most patients were male [n = 194 (79.8%)] and mean [standard deviation (SD)] age was 41.2 (12.3) years. At baseline, nearly all patients had PASI <3 [94.2% (229/243)] and Investigator’s Global Assessment 0/1 [91.4% (222/243)]. DLQI scores gradually increased after guselkumab withdrawal, from a mean (SD) of 4.8 (4.4) on the index date to 5.2 (4.6) at Week 12 and 7.2 (6.0) at Week 24 [mean (SD) change: 0.4 (4.5) at Week 12; 2.5 (6.2) at Week 24]. Overall, 5.8% (14/241) of patients had a psoriasis relapse. The mean (SD) OTD was 157.6 (1.1) days; the median OTD was not reached. Patients in this post-PAC study in China experienced gradual deterioration of HRQoL after guselkumab withdrawal. Only a small proportion of patients experienced a psoriasis relapse during 24 weeks of follow-up, suggesting treatment response was generally maintained after guselkumab withdrawal. Results from the planned interim analysis were not conclusive due to the limited duration of follow-up; long-term data analysis will be conducted upon study completion at Week 48.

Anogenital psoriasis: clinical picture and therapy

Psoriasis presenting with anogenital lesions is an important medical and social problem that is not sufficiently covered in the literature. The genitals and perianal area are involved in severe plaque and inverse psoriasis. Occasionally, the disease can be localized only in the anogenital zone. Diagnosis of psoriasis with localization on the genitals and/or perianal area is difficult, which is associated with the anatomical and physiological characteristics of the affected area. The manifestations of psoriasis become exudative, infiltration of papules and plaques is expressed little, the borders of rashes lose clarity, peeling on the skin is expressed weakly, in the depth of the folds due to maceration and friction is absent. Subjectively significant localization of the process, its prolonged course, pruritus lead to significant violations of the quality of life of patients and serve as prerequisites for the formation of anxiety-depressive disorders and sexual dysfunction Diagnosis and treatment of anogenital psoriasis presents significant challenges. Clinical guidelines tend to emphasize external therapy with topical corticosteroids and calcineurin inhibitors; in recent years, the efficacy of genetically engineered biological agents, including interleukin-17 inhibitors and phosphodiesterase-4 inhibitors, has been considered. The presented review systematizes information about anogenital psoriasis, peculiarities of its epidemiology, clinical picture, diagnosis and approaches to therapy.

Post-Marketing Safety of Ustekinumab Based on 14-Year Follow-Up in Danish National Patient Data.

Psoriasis (PsO), a chronic inflammatory skin disorder affecting a substantial proportion of populations globally, often necessitates systemic treatment including biologics. This 14-year cohort study, based on Danish national register data, aimed to investigate the enduring safety profile of ustekinumab compared to other systemic psoriasis treatments. Using comprehensive Danish national register data, this study scrutinized patients diagnosed with psoriasis or psoriatic arthritis (PsA) who received ustekinumab. The treatment group comparators were non-biological systemic treatment (non-biologic), tumor necrosis factor α inhibitor medicine groups (TNF-α), interleukin (IL)-17 inhibitors (IL-17), and IL-23 inhibitors (IL-23). The study periods for comparisons were 2009-2022 for non-biologic and TNF-α, 2015-2022 for IL-17, and 2018-2022 for IL-23. Outcomes were malignancies, cardiovascular events, serious infections, and serious hypersensitivity reactions. Cox proportional hazards regression models were employed to analyze two estimands: a standard intention-to-treat (ITT) estimand and a continuous-index-treatment (CIT) estimand, which considered switch and re-initiation of treatments within individuals. Users of ustekinumab were found to be younger on average, with an average age of 45.1 years compared to 51.6, 47.2, 49.0, and 48.4 years in the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Also, 57.3% of the ustekinumab users were male, compared to 46.7%, 48.9%, 50.9%, and 58.3% for the non-biologic, TNF-α, IL-17, and IL-23 groups, respectively. Although the hazard ratio estimates varied across comparators, ustekinumab was found to be safe: regardless of PsA status, no discernible safety signals in terms of malignancy, MACE, severe infections, or severe hypersensitivity reactions were observed for ustekinumab when compared to the treatment comparators. The present study corroborated the enduring safety of ustekinumab in the context of PsO treatment.

Intradermal implantation of methotrexate-loaded puerarin-gelatin hydrogel via bubble-generating microneedles for psoriasis treatment

Methotrexate (MTX) is a primary treatment for moderate to severe psoriasis, but conventional oral or subcutaneous delivery has limitations, including poor drug targeting, side effects, and low patient compliance. This study introduces implantable hydrogel microneedles (HMNs) made from photo-cross-linked gelatin methacryloyl (GelMA) and puerarin (Pue), a traditional Chinese medicine, for intradermal and sustained MTX delivery. The ratio of Pue to GelMA significantly influenced the morphology, mechanical strength, MTX release profiles, and degradation behavior of the HMNs. After insertion into the skin, the backing layer of the microneedles, which incorporates effervescent agents (NaHCO3 and citric acid), rapidly generates gas bubbles (CO₂) upon contact with skin interstitial fluid, facilitating the immediate separation of the HMNs from the backing and their implantation into skin tissue as MTX reservoirs. HMNs with 1.5 % w/v Pue and 20 % w/v GelMA achieved a 10-day MTX release in vivo. In vivo studies demonstrate that MTX-loaded Pue/GelMA HMNs significantly enhance therapeutic outcomes in alleviating psoriasis symptoms and downregulating psoriasis-associated cytokines due to the synergistic effects of MTX and Pue, outperforming oral administration, subcutaneous injection, and GelMA HMNs containing either Pue or MTX alone. This HMN patch offers great promise for improving psoriasis treatment and patient adherence.

Assessment of the level of anxiety-depressive disorders, quality of life, and therapy adherence in patients with plaque psoriasis

Relevance. The treatment of moderate and severe psoriasis poses significant challenges in clinical practice. This article is devoted to the analysis of real-world clinical practice in the treatment of plaque psoriasis, factors causing relapses of plaque psoriasis, the prevalence of anxiety and depressive disorders, and the assessment of the quality of life of patients with psoriasis using various systemic medications among patients who were observed in dermatovenereological dispensaries of the Central Federal District during the period 2022–2023.Objectives. To determine the optimal drug therapy for patients with plaque psoriasis based on comprehensive pharmacoepidemiological, clinical, compliance, and medication adherence assessments.Materials and methods. Retrospective comparative analysis of the medical records of 336 patients with plaque psoriasis (L40.0), moderate and severe. Two comparison groups: Group I — 166 patients receiving methotrexate and Group II — 170 patients receiving genetically engineered drugs. Patients were surveyed by physicians to confirm their therapy compliance. The levels of anxiety and depression were assessed using the HADS scale, and quality of life was assessed using the dermatological quality of life index — DLQI.Results. The highest rate of adherence to therapy (>80%) was recorded in the group of patients undergoing therapy with genetically engineered drugs and who had a high level of anxiety (r=0.202, p<0.05). In the group of patients with average adherence to the applied genetic engineering therapy (30–80%), a higher level of anxiety was associated with reduced adherence to treatment (r=–0.202, p<0.05). Average adherence to methotrexate (r =–0.249, p<0.05).Conclusions. An increased level of anxiety in patients undergoing therapy with genetically engineered drugs increased their adherence to treatment (r=0.202, p<0.05). The worse the quality of life of patients undergoing therapy with genetically engineered drugs, the less adherence.

NLRC3 affects the development of psoriasis by modulating the NF-κB signaling pathway mediated inflammatory response through its interaction with TRAF6

ObjectiveThe function and mechanism of NOD-like receptor family CARD-containing 3 (NLRC3) in psoriasis are not yet reported, even though it plays a crucial role in innate and adaptive immunity by inhibiting inflammation. Therefore, this research aims to investigate the role and mechanism of NLRC3 in psoriasis. MethodsHaCaT cells were induced to form a psoriasis cell model using 20 ng/mL IL-1β, 20 ng/mL IL-17A, 20 ng/mL IL-23, 50 ng/mL TNF-α, and 20 ng/mL oncostatin M. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were assessed to determine the proliferation, cell cycle, and apoptosis of HaCaT cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the knockdown efficiency of NLRC3 and TRAF6 interfering RNA in HaCaT cells. Western blot analysis was performed to determine the expression levels of NLRC3, TRAF6, and proteins associated with the NF-κB signaling pathway. A mouse model of psoriasis-like dermatitis was established by evenly applying miquimod cream (62.5 mg/day) to both ears. Hematoxylin-eosin staining was used to measure ear thickness and inflammatory infiltrates in mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL were performed to detect cell proliferation and apoptosis. Interactions between NLRC3 and TRAF6 were predicted using the STRING database (https://cn.string-db.org/). Co-Immunoprecipitation was used to confirm interactions between NLRC3 and TRAF6. Ubiquitination of TRAF6 was assessed by Western blot. ResultsKnockdown of NLRC3 expression promoted cell proliferation and inhibited cell apoptosis in HaCaT cells. In vivo, knockdown of NLRC3 expression significantly increased the infiltration of inflammatory cells and the proliferation of Ki-67 positive cells within mouse ear epidermis, while decreasing the number of apoptotic cells. NLRC3 interacted with TRAF6 and influenced its K63 ubiquitination level. Knockdown of TRAF6 expression resulted in increased cell proliferation and decreased cell apoptosis in HaCaT cells. In vivo, knockdown of TRAF6 expression led to a significant increase in inflammatory cell infiltration and Ki-67 positive cells in mouse ear epidermis, and a decrease in apoptotic cells. Inhibiting the NF-κB signaling pathway alleviated the progression of psoriasis, and interfering with TRAF6 activated the NF-κB signaling axis, contributing to the onset and advancement of psoriasis. ConclusionNLRC3 affects the occurrence of psoriasis by regulating TRAF6 and influencing the NF-κB signaling axis-mediated inflammatory response. This finding offers a theoretical foundation for the treatment of psoriasis.

Clinical effect of Secuchiumab in the Treatment of Psoriasis

Psoriasis is a chronic and recurrent skin condition triggered by the immune system, with a relatively high prevalence. The primary clinical manifestation of this condition is the appearance of red and swollen patches of skin covered with silvery scales, often accompanied by itching and a feeling of tightness. In addition to skin symptoms, psoriasis patients frequently experience systemic conditions such as arthritis and heart disease. Recent research has shown a strong link between psoriasis and metabolic syndrome. The main symptoms of metabolic syndrome include hypertension, high blood sugar, elevated cholesterol levels, and abdominal obesity. These issues not only increase the risk of cardiovascular diseases but may also exacerbate the severity of psoriasis. Traditional treatments for psoriasis have included topical medications, phototherapy, and symptomatic relief therapies, with methotrexate being a common drug. While these conventional methods can partially improve the skin condition of psoriasis patients with metabolic syndrome, they are not effective at modulating immune system function or correcting metabolic imbalances. As our understanding of the pathophysiology of psoriasis deepens, biologic therapies have increasingly become a research focus. Secukinumab, a monoclonal antibody targeting interleukin-23, inhibits specific inflammatory pathways and offers a new, potentially more effective treatment option for psoriasis patients with metabolic syndrome.

Educational video assistance in shared decision-making for psoriasis: Effectiveness and outcomes.

Psoriasis is a chronic inflammatory skin condition associated with significant comorbidities that impact quality of life. Effective patient engagement through shared decision-making (SDM) is crucial for optimal management. This study aimed to evaluate the effectiveness of adding clinician-created educational videos in enhancing patient knowledge and engagement during SDM for psoriasis treatment. Forty-eight patients with moderate to severe psoriasis participated in this single-center study. After reading an educational pamphlet, patients took a knowledge assessment test. Subsequently, they watched an educational video and completed a second test using the same questions. Feedback questionnaires on the video and the SDM process were also administered. Paired t tests revealed that postpamphlet plus video test scores (mean ± SD: 86.25 ± 17.58) were significantly higher than postpamphlet scores (72.08 ± 26.33, p < 0.0001). Older patients, in particular, showed greater improvement in comprehension after watching the video. Descriptive analysis of the feedback questionnaire on the video indicated strong agreement (average score: 4.240 ± 0.816 on a five-point Likert scale) regarding its greater effectiveness compared with the pamphlet in aiding SDM. Patients also rated the video-assisted SDM process positively (average score: 4.521 ± 0.5443 on a five-point Likert scale), highlighting increased trust and improved communication with healthcare providers. These findings underscore the value of video-assisted SDM in patient education and decision-making processes, potentially improving treatment outcomes and patient satisfaction in dermatologic care.

Dimethyl fumarate ameliorates chronic graft-versus-host disease by inhibiting Tfh differentiation via Nrf2.

Chronic graft-versus-host disease (cGVHD), characterized by chronic tissue inflammation and fibrosis involving multiple organs, remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF) is an anti-inflammatory drug approved for the treatment of multiple sclerosis and psoriasis. We previously reported that DMF effectively inhibits acute GVHD (aGVHD) while preserving the graft-versus-leukemia effect. However, the role of DMF in cGVHD progression remains unknown. Here, we found that DMF administration significantly suppresses follicular helper T cell (Tfh) differentiation, and germinal center formation and alleviates disease severity in different murine cGVHD models. Mechanistically, DMF treatment downregulates IL-21 transcription by activation of Nrf2, thus orchestrating Tfh-related gene programs both in mice and humans. The inhibitory role of DMF on Tfh cell differentiation was diminished in Nrf2 deficient T cells. Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving the way for the treatment of cGVHD in the clinic.

Hyaluronan-Cholesterol nanogels embedding betamethasone for the treatment of skin inflammatory conditions

Topical application of the glucocorticoid betamethasone (BM) is a common treatment for inflammatory-related skin diseases, such as psoriasis. However, enhancing its bioavailability remains challenging due to poor skin permeability. Herein, we developed and evaluated hyaluronan-cholesterol (HACH) based nanohydrogel systems (NHs) and NHs-Carbopol formulation for dermal delivery of BM. Various parameters were investigated including particle size, surface charge, encapsulation efficiency, in vitro drug release kinetics and stability. The HACH-based NHs demonstrated high encapsulation efficiency, with apparent solubility improved up to 9-fold, small size (∼190 nm) and good stability at 4 ℃ and during long-term storage. Besides, the NHs-Carbopol formulation exhibited excellent rheological properties and an occlusive effect suitable for cutaneous application. Both in-vitro (using Strat-M® membrane) and ex-vivo (using pig ear skin) permeation studies revealed that these formulations significantly improved skin permeation and drug retention in the deeper layers of the epidermis and dermis, making it advantageous for the topical delivery of BM in psoriasis treatment. Moreover, the NHs system demonstrated potential anti-psoriatic activity by downregulating the proinflammatory cytokines in vitro in human keratinocytes (HaCaT cell line) and in an ex vivo 3D skin tissue model (EpiDerm-FT™).

LGR4 Deficiency Aggravates Skin Inflammation and Epidermal Hyperplasia in Imiquimod-Induced Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterised by inflammatory cell infiltration, keratinocyte hyperproliferation and increased neovascularization. Despite extensive research, the precise mechanisms underlying psoriasis pathology and treatment strategies remain unclear because of a complex aetiology and disease progression. Hence, in this study, we aimed to identify potential therapeutic targets for psoriasis and explore their effects on disease progression. We observed that G protein-coupled receptor LGR4 attenuates psoriasis progression. Bioinformatics analysis of publicly available clinical data revealed lower LGR4 expression in the skin lesions of patients with psoriasis than in their non-lesioned skin. Both invitro (HaCaT cell) and invivo (mouse) models confirmed this phenomenon. The Lgr4-knockout mouse model further confirmed that LGR4 plays a positive role in psoriasis progression. Specifically, Lgr4 knockout promoted the secretion of inflammatory factors, accumulation of local immunocyte infiltration in skin lesions, and keratinocyte proliferation. In conclusion, we demonstrated that LGR4 is critical to limiting psoriasis progression, suggesting that it is a viable target for the clinical management of this skin condition.

Drug Survival and Safety of Biosimilars Compared with Originator Adalimumab for Psoriasis: A Multinational Cohort Study.

The lack of evidence under routine clinical settings limited the widespread adoption of adalimumab biosimilars for psoriasis treatment. This study compared the drug survival and safety of adalimumab biosimilars to Humira for psoriasis treatment. We conducted a prevalent new-user cohort study using data from the French National Health Data System (SNDS), the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), and the Spanish Registry of Systemic Therapy in Psoriasis (BIOBADADERM). Adalimumab-naïve patients initiating adalimumab biosimilars (new users) were compared with Humira new users. Patients switching from Humira to biosimilars (switchers) were compared with those who continued Humira treatment. Patients were matched 1:1 based on previous adalimumab exposure time to create equal-sized cohorts of biosimilar and Humira users. Co-primary outcomes included drug discontinuation and serious adverse events (SAEs). Hazard ratios (HR) were calculated using Cox proportional hazard models. Meta-analyses using random effect models were performed to combine results from 3 databases. 7387 biosimilar new users and 3654 switchers were matched and compared with Humira users. No differences in all-cause discontinuation were found between biosimilars and Humira new users (HR: 0.99, 95% CI: 0.94-1.04). Switching from Humira to biosimilars was associated with a higher discontinuation rate compared to remaining on Humira (HR: 1.35, 95% CI: 1.19-1.52). Similar results were observed for discontinuation due to ineffectiveness or adverse events. Risks of SAEs were similar between biosimilar new users and Humira new users (Incidence rate ratio IRR: 0.91, 95% CI: 0.80-1.05) or between switchers and continuous Humira users (IRR: 0.92, 95% CI: 0.83-1.01). Adalimumab biosimilars can be considered viable alternatives to Humira for new patients with comparable effectiveness and safety. However, due to the higher likelihood of discontinuation, patients who switch from Humira to biosimilars may require closer monitoring and support.

Real-world safety of spesolimab in generalized pustular psoriasis: Evidence from an expanded access program in Argentina

Introduction: Generalized pustular psoriasis (GPP) is a heterogeneous, systemic, neutrophilic, inflammatory disease associated with chronic symptoms and periods of flaring. Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved for the treatment of flares in adult patients with GPP in Argentina (17 Aug 2023).1 Here, we present safety data from a real-world expanded access program (EAP: 22 Feb 2023–10 Jan 2024) in Argentina which provided early access to spesolimab intravenous (IV) for GPP patients presenting with a flare with no other treatment options. Methods: Patients (18–75 years old) diagnosed with GPP received a 900mg dose of spesolimab IV for flare treatment, with an optional second dose after 1 week for persistent flare symptoms. Adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were recorded for up to 16 weeks after the last spesolimab infusion.Results: Six female patients were treated with spesolimab IV (1 dose, n=2; 2 doses, n=4).Mean (standard deviation [SD]) age: 49.3 (11.5) years (range: 30–60 years), mean (SD) body mass index: 28.1 (5.8) kg/m2, and mean (SD) follow-up: 3.85 (0.11) months. At baseline, GPP had been diagnosed within ≤1 year (n=2), &gt;1–≤5 years (n=1), and &gt;10 years (n=3). Reported flare triggers were stress (n=2), treatment withdrawal (n=1), heat (n=1), lack of current treatment efficacy (n=1), and unknown (n=1). At baseline, 4 patients had ≥1 comorbidity, including hypertension (n=2), tachycardia, hypothyroidism, chronic gastritis, arthritis, and epilepsy (each n=1). Five patients reported use of ≥1 concomitant medication (including immunosuppressants and corticosteroids) during the EAP; 1 patient had discontinued ustekinumab (biologic). Three patients had signs of plaque psoriasis within the past year and had received treatment for plaque psoriasis; 1 patient had ongoing plaque psoriasis. In total, 4 patients had any AEs (all 4 patients had mild AEs [influenza, catarrh, pruritis, rash, pain] and 1 of these patients also had a moderate AE [headache]). Two drug-related AEs (pruritus and rash) were reported in 1 patient. The hypersensitivity event (rash) was non-serious. There were no reports of SAEs, AESIs, or AEs that led to discontinuation/death. Conclusion: Spesolimab showed a favorable safety profile in patients with GPP, including patients with comorbidities and those taking concomitant medication. Findings were comparable with a Phase 2a randomized controlled trial in patients with GPP flares (EFFISAYIL 1).