Treatment Of Psoriasis Research Articles

The Potential Anti-psoriatic Effects of Andrographolide: A Comparative Study to Topical Corticosteroids.

Andrographolide (AP), a bioactive anti-inflammatory compound of Sambiloto, inhibits NF-κB, TNF-α, and interleukin IL-6. Nowadays, molecular docking simulation between AP and dexamethasone against NF-κB receptor presented the energy AP higher than dexamethasone. This becomes a potential treatment for psoriasis. This manuscript reported the effectiveness of AP from Sambiloto in treating psoriasis compared to topical steroids. This study conducted TLC analysis of AP content and its metabolite impurities, emulgel formulation, molecular docking, in-silico skin toxicity study, and in-vivo anti-psoriatic activity. This was a combination study of an in-silico study and an in-vivo study. This in-silico study was analyzed through multivariate statistical analysis (PCA) to elucidate the data constellation relationship of andrographolide derivatives with several target proteins. The intervention was performed in seven days. The PASI score, molecular parameters (IL-6, IL-17, VEGF, and TNF-a levels), and histopathological findings were assessed. Molecular docking results revealed andrographolide to exhibit a relatively high binding affinity towards IL-6, NF-kB, and TNF-α which is comparable to the corticosteroids, andrographolide also shares similar residue interaction profile with each of the respective protein's native ligand. In the in-vivo study, we found several parameters statistically significantly different regarding the intervention, including final PASI score (p = 0.017), redness (p = 0.017), scale (p = 0.040), thickness (p = 0.023), total histopathology of psoriasis score (p = 0.037), keratin layer score (p = 0.018). Emulgel AP 0.1% could lower the anti-inflammatory agent, which is vital to psoriasis progression.

Management of Psoriasis Patients with Serious Infectious Diseases.

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

The impact of temperature on vascular function in connection with vascular laser treatment

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment.

Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1–3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with Genome-Wide Association (GWAS) studies showing that many psoriasis risk genes lie along the IL-23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. This review is focused on the IL-23/Th17 axis, providing an insight into key cell types, cytokines, and intracellular signaling pathways involved. This includes examination of currently available biological treatments, time to relapse post drug withdrawal, and rates of primary/secondary drug failure, showing the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely to reduce the burden of disease for the longest period possible.

Evaluation of the efficacy and safety of cold laser (Diode 808 nm) therapy in the treatment of localized plaque psoriasis: clinical, dermoscopic and ultrastructural study

Background Psoriasis is a chronic, recurring, and immune-mediated inflammatory skin disease. Throughout the period of the last few decades, phototherapy has become widely used in treating stable psoriatic lesions. For the treatment of psoriasis, several light/laser therapies with distinct modes of action have been developed. Cold laser therapy might be an effective therapeutic choice for localized plaque psoriasis. Objective To assess the safety and efficacy of cold laser therapy clinically and microscopically in localized plaque psoriasis treatment. Patients and methods 40 patients with localized mild plaque psoriasis were selected from the Dermatology and Venereology outpatient clinic–Tanta University Hospitals and enrolled in the clinical trial. They were treated by cold laser 808 nm wavelength (Endolaser 422, Enraf–nonious B.V. Rotterdam, Netherlands) one session for 10 min on each plaque twice weekly separated by 2 days until clinical cure or for a maximum of 8 weeks. Evaluation was done immediately after the last session by taking the average of three blinded dermatologists of the photos, the modified Psoriasis Area and Severity Index [mPASI], dermoscopic examination, patients’ satisfaction scale and histopathological and electron microscopic examination of punch biopsy specimens taken before and after the end of treatment from psoriatic lesions in four patients only. Results There was a statistically significant clinical improvement after the end of treatment compared with before treatment as 16 patients (40%) showed excellent improvement, 8 patients (20%) showed good improvement, 9 patients (22.5%) showed mild improvement, and 7 patients (17.5%) showed poor improvement. As regard mPASI, a statistically significant decrease in mPASI was found after the end of treatment (P<0.001). Regarding dermoscopic examination, a statistically significant reduction in the percentage of patients showing dermoscopic red dots and white scales after the end of treatment (P<0.01). As regard the patients’ satisfaction scale, 82.5% of patients were satisfied from the results. Histopathological and ultrastructural evaluation revealed normalization of the psoriatic microscopic changes with cold laser. Conclusion The use of cold laser therapy for the management of localized mild plaque psoriasis is safe, tolerable, effective, and can be used as an alternative therapy for psoriasis.

Challenges in Immunomodulation for Psoriasis: Recent Advancements and Need of Therapies

Abstract: Psoriasis is a chronic immune-mediated skin disorder affecting millions worldwide. The pathogenesis of psoriasis involves dysregulated immune responses characterized by aberrant activation of T cells and proinflammatory cytokines. Immunomodulation has emerged as a promising therapeutic approach for managing psoriasis, aiming to restore immune homeostasis. However, despite significant advancements, challenges persist in developing effective immunomodulatory therapies. This abstract reviews recent developments in psoriasis immunomodulation, encompassing novel targets and therapeutic modalities. Advances in biologics targeting interleukins (IL) and their receptors, such as IL-17, IL-23, and IL-12/23, have demonstrated substantial clinical efficacy. Additionally, small molecules that inhibit Janus kinases (JAK) and phosphodiesterase 4 (PDE4) have shown promise in regulating immune responses. Despite these advancements, certain limitations hinder the success of immunomodulatory therapies. Treatment resistance, safety concerns, and high costs remain critical challenges. Furthermore, a deeper understanding of the complex immunopathogenesis of psoriasis is essential for developing targeted and personalized therapies. In conclusion, immunomodulation has revolutionized the management of psoriasis, offering remarkable improvements in patient outcomes. Continued research and innovative therapeutic strategies are needed to overcome current challenges and pave the way for more efficient, safe, and accessible treatments for psoriasis.

Formulation and validation on UV spectroscopy of Herbosomes loaded Mahonia aquifolium cream for psoriasis

Herbosome technology enhances the bioavailability of herbal excerpts. Herbosome act as the ground between the new delivery system and conventional delivery system. It's a complex fashion applied to phytopharmaceuticals for the improvement of bioavailability of herbal excerpt for medicinal operations. This composition overviews about herbosome technology, recent advance, their operation for colorful standardized herbal excerpts and aims to give complete of natural active constituents and phospholipid (phosphatidylcholine, phosphatidylserine etc.) which increases immersion of herbal excerpt. Herbosome is the new arising scientific information, characterization about herbosomes as a promising drug delivery system. Psoriasis is an inflammatory skin condition characterized by scaling with inflammation (pain, edema, warmth, and redness) that results in regions of thick, red skin covered in silvery scales. These spots can be itchy or painful. Systemic treatment, topical therapy, and phototherapy are all now used to treat psoriasis. These treatments have a variety of negative and perhaps fatal side effects. Patients with psoriasis are more likely to acquire other conditions such as psoriatic arthritis, anxiety and depression, cancer, metabolic syndrome, cardiovascular disease, and Crohn's disease. The majority of people use herbal medicine because it is readily available, inexpensive, and effective. Many plants have promising features, including significant results in the treatment of psoriasis. The present study plans to emphasize such plants, herbal formulations, and associated therapy, which could add value to the development of a better, safe, and efficacious formulation to treat psoriasis that may help new researchers in this field

The Therapeutic Potential of Essential Oils in Managing Inflammatory Skin Conditions: A Scoping Review

Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils (EOs). This scoping review aims to generate a broad overview of the EOs used to treat inflammatory skin conditions, namely, acne vulgaris, dermatitis and eczema, psoriasis, and rosacea, in a clinical setting. The quality, efficacy, and safety of various EOs, as well as the way in which they are prepared, are reviewed, and the potential, as well as the limitations, of EOs for the treatment of inflammatory skin conditions are discussed. Twenty-nine eligible studies (case studies, uncontrolled clinical studies, and randomized clinical studies) on the applications of EOs for inflammatory skin conditions were retrieved from scientific electronic databases (PubMed, Embase, Scopus, and the Cochrane Library). As an initial result, tea tree (Melaleuca alternifolia) oil emerged as the most studied EO. The clinical studies with tea tree oil gel for acne treatment showed an efficacy with fewer adverse reactions compared to conventional treatments. The uncontrolled studies indicated the potential efficacy of ajwain (Trachyspermum ammi) oil, eucalyptus (Eucalyptus globulus) oil, and cedarwood (Cedrus libani) oil in the treatment of acne, but further research is required to reach conclusive evidence. The placebo-controlled studies revealed the positive effects of kānuka (Kunzea ericoides) oil and frankincense (Boswellia spp.) oil in the treatment of psoriasis and eczema. The quality verification of the EO products was inconsistent, with some studies lacking analyses and transparency. The quality limitations of some studies included a small sample size, a short duration, and the absence of a control group. This present review underscores the need for extended, well-designed clinical studies to further assess the efficacy and safety of EOs for treating inflammatory skin conditions with products of assured quality and to further elucidate the mechanisms of action involved.

Therapeutic Effects of 30 nm Cyclosporin A-Loaded Nanoparticles Using PLGA-PEG-PLGA Triblock Copolymer for Transdermal Delivery in Mouse Models of Psoriasis

This study aimed to evaluate the effectiveness of poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) as a drug carrier in the treatment of psoriasis. Nanoparticles containing cyclosporin A (CsA) were prepared, and their cytotoxicity and skin irritation properties were investigated. These results revealed that the nanoparticles themselves had no obvious cytotoxicity or skin irritation effects. Furthermore, it was shown that loading CsA into nanoparticles promoted its cellular uptake. The therapeutic effect of CsA-loaded PLGA-PEG-PLGA nanoparticles on psoriasis was evaluated using a mouse model of psoriasis induced by imiquimod. In psoriatic skin, we confirmed that nanoparticles penetrate deep into the skin. Furthermore, it was suggested that by using PLGA-PEG-PLGA, drug carriers could reach the dermal layer, which is the target site for psoriasis treatment. The observation of skin sections after the treatment experiment showed that excessively proliferated keratinocytes were restored to an almost normal state by using PLGA-PEG-PLGA nanoparticles as drug carriers. Additionally, the quantitative measurement results for cytokines revealed that the levels of TNF-α, IL-17A, and IL-22 were significantly decreased compared with those of the group to which CsA suspended in a 20% ethanol solution was administered. These results indicate that PLGA-PEG-PLGA nanoparticles are promising drug carriers for the transdermal administration of CsA.

Discussion on the Treatment of Psoriasis by Sweating and Tongxuan Theory Based on the Perspective of "Visceral Organs and Metaphysical Organs

Discussion on the Treatment of Psoriasis by Sweating and Tongxuan Theory Based on the Perspective of "Visceral Organs and Metaphysical Organs

Anti-ROS and NIR-II-Responsive Hyaluronic Acid Microneedle Loaded With Baicalin Nanoparticles for Treatment of Psoriasis.

In this work, a natural medicine, baicalin, is designed for the treatment of psoriasis with the aid of hyaluronic acid (HA)-based MNs patches. This is also to improve the solubility of baicalin and increase its residence time in infected part, which is made into nanoparticles by complexation with humic acid and Eu2+. The baicalin nanoparticles loaded-MNs exhibit satisfactory rigidity, minimum injury, and controlled drug delivery. The anti-reactive oxygen species (anti-ROS) and anti-inflammatory action are verified by the effective scavenging oxygen and nitrogen radicals. In addition, the loading of baicalin nanoparticles brings remarkable photothermic effect to the MNs, enabling the device to release a controlled drug under near-infrared region II (NIR-II) laser irradiation. With the aid of NIR-II laser, the baicalin-mediated treatment of psoriasis is significantly improved by expediting radical scavenging and suppressing inflammation. The design of baicalin MNs provides a new idea for the treatment of chronic disease.

Inhibition of the JAK-STAT Pathway in the Treatment of Psoriasis: A Review of the Literature

Psoriasis is a highly prevalent dermatological disease associated with an increased systemic inflammatory response. In addition, joint involvement is also present in around 20% of patients. Therefore, treatment modalities used in this condition should be simultaneously effective at improving skin manifestations, reducing inflammation, and addressing psoriatic arthritis when present. Twenty years ago, the introduction of biologic treatments for psoriasis was a turning point in the management of this condition, offering an effective and reasonably safe option for patients whose disease could not be adequately controlled with conventional therapies. At the moment, Janus Kinase inhibitors (JAKis) are a new class of promising molecules in the management of psoriasis. They are orally administered and can show benefits in patients who failed biologic therapy. We conducted a scoping review in order to identify randomized-controlled trials that investigated different JAKis in patients with plaque psoriasis and psoriatic arthritis, with an emphasis on molecules that have been approved by the European Medicines Agency and the Food and Drug Administration. The added value of this study is that it collected information about JAKis approved for two different indications, plaque psoriasis and psoriatic arthritis, in order to provide an integrated understanding of the range of effects that JAKis have on the whole spectrum of psoriasis manifestations.

Impact of residual skin lesions and previous biologic treatment failure on patient-reported outcomes in patients with psoriasis receiving biologic treatment.

Recent advances in biologic treatments have made clear skin a realistic treatment goal for psoriasis. However, clear skin may not uniformly translate to an absence of impact on patients' quality of life. This retrospective observational study aimed to elucidate the factors influencing patient-reported outcomes in patients with psoriasis who have demonstrated successful clinician-reported outcomes on using biologics. A total of 96 patients who have achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI) scores with ≥6 months of biologic treatment were included. Their median PASI score was 0.4, with 37.5% having achieved PASI 100 (clear skin). Furthermore, 47.9% reported no impact of psoriasis on their quality of life (Dermatology Life Quality Index [DLQI] score 0 or 1), while 52.1% reported a negative impact (DLQI score ≥2). Notably, 28.1% of the participants had a history of biologic treatment failure, defined as the inability to achieve or sustain a 75% PASI improvement with the previously used biologic agent. Multivariable logistic regression analysis revealed a positive association between achieving PASI 100 and reporting no impact of psoriasis on quality of life (adjusted odds ratio [aOR] 3.88, 95% confidence interval [CI] 1.49-10.91, P = 0.007). Conversely, prior biologic treatment failure was negatively associated with reporting no impact of psoriasis on quality of life (aOR 0.13, 95% CI 0.02-0.65, P = 0.023). Furthermore, among patients with clear skin, those with experience of previous biologic treatment failure reported significantly lower quality of life than those without such experience (P = 0.033). In conclusion, minimal residual skin lesions and prior biologic treatment failure were associated with poorer patient-reported outcomes in patients with psoriasis. Opting for a biologic agent with the highest predicted efficacy, rather than pursuing a "step-up" approach with a higher possibility of treatment failure, may be a more suitable strategy in the biologic treatment of psoriasis.

An update on topical therapies for psoriasis.

Topical therapies are a mainstay of treatment for mild psoriasis and may be a useful adjunct in treatment of moderate-to-severe psoriasis. This review summarizes recent advances in topical therapies for psoriasis and currently available treatments. Topical aryl hydrocarbon receptor modulators (tapinarof) and topical phosphodiesterase-4 inhibitors (roflumilast) have been proven effective in randomized controlled trials for psoriasis. Although topical JAK inhibitors have also been studied, none are currently licensed for treatment of psoriasis. Topical corticosteroids and vitamin D analogues remain the most commonly used and widely available topical treatments for psoriasis. Cost may limit use of novel topical agents. Although the novel topical agents tapinarof and roflumilast are licensed for treatment of psoriasis by the FDA in the United States, they have not yet been licensed in Europe, and it remains to be seen whether they will be limited by cost.

P171 Bimekizumab impact on core group for research and assessment of psoriasis and psoriatic arthritis domains for patients with psoriatic arthritis: 52-week results from four phase 3 studies

Abstract Background/Aims The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (PsA; GRAPPA) domainbased treatment recommendations for PsA focus on six domains: peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis, and PsA-related conditions: uveitis and IBD. Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits IL17F in addition to IL17A, has superior clinical efficacy vs placebo (PBO) to Week (Wk)16 in phase 3 clinical trials of PsA patients. In patients with psoriasis, superior skin domain efficacy was demonstrated versus secukinumab (IL-17A inhibitor), ustekinumab (IL-12/23 inhibitor), and adalimumab (TNF inhibitor [TNFi]). Methods Included patients received subcutaneous BKZ 160 mg or PBO every 4-wks (Q4W) in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drugs [bDMARD]naïve patients with PsA), BE COMPLETE (NCT03896581; patients with PsA who were TNFiinadequate responders [TNFiIR]), BE MOBILE 1 (NCT03928704; nonradiographic axial spondyloarthritis [nr-axSpA]) and BE MOBILE 2 (NCT03928743; radiographic [r-]axSpA [i.e. ankylosing spondylitis]). BE OPTIMAL included a reference arm (adalimumab 40 mg Q2W) to Wk52; data not shown. From Wk16, all PBO-randomised patients received BKZ 160 mg Q4W to Wk52 (PBO/BKZ). Wk16 completers from BE COMPLETE entered BE VITAL (NCT04009499; openlabel extension). Outcomes are reported by GRAPPA domain as change from baseline and/or responder rate. Missing data were imputed using non-responder (binary) or multiple (continuous) imputation. Results Wk52 completion was high (BE OPTIMAL: 770/852 [90.4%], BE COMPLETE: 347/400 [86.8%], BE MOBILE 1: 220/254 [86.6%], BE MOBILE 2: 298/332 [89.8%]). Baseline demographics and disease characteristics were previously reported. Across all GRAPPA domains, improvements from Wk16 were sustained at Wk52 in BKZ-treated patients across all studies. Individual domain responses were generally consistent between bDMARD naïve and TNFi-IR patients; results from BE MOBILE 1 and 2 demonstrated BKZ efficacy in patients with axSpA (Table). Responses were generally consistent between BKZ and PBO/BKZ patients at Wk52. To Wk52, there were low rates of adjudicated IBD (2 [0.2%] in BE OPTIMAL) and no instances of uveitis. Conclusion Treatment with BKZ resulted in robust and sustained improvements across GRAPPA domains to Wk52 for both bDMARD naïve and TNFi-IR patients with PsA; results from patients with axSpA support efficacy in the axial domain. Disclosure J.F. Merola: Consultancies; AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. Other; Investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. P.J. Mease: Consultancies; AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, Acelyrin, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma. A. Deodhar: Consultancies; AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, UCB Pharma. Member of speakers’ bureau; Janssen, Novartis, Pfizer. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer, UCB Pharma. B. Ink: Shareholder/stock ownership; AbbVie, GSK, UCB Pharma. Other; Employee of UCB Pharma. C. Fleurinck: Other; Employee of UCB Pharma. R. Bajracharya: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. J. Coarse: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. L.C. Coates: Consultancies; AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer, UCB Pharma. Member of speakers’ bureau; AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, UCB Pharma. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB Pharma.

P172 An integrated safety analysis of treatment-emergent fungal infections in patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis treated with ixekizumab from 26 clinical studies

Abstract Background/Aims Interleukin (IL)-17 plays a role in host defense against common extracellular pathogens, including fungi. Treatment with IL-17 inhibitors has been associated with fungal infections. Ixekizumab (IXE) is an anti-IL-17A monoclonal antibody approved for the treatment of psoriasis (PsO) in adults and children, psoriatic arthritis (PsA) in adults, and axial spondyloarthritis (axSpA) in adults. This integrated post-hoc analysis investigates treatment-emergent fungal infections in IXE-treated patients across the approved indications. Methods Safety data on fungal infections were pooled from the IXE paediatric and adult clinical trial programs, comprising 26 clinical studies. Here, we describe the types of fungal infections, number of infections, recurrence (defined by at least two separate events irrespective of location), severity (defined at the investigator’s discretion), events that lead to discontinuation, and anti-fungal medications. Data are presented as frequency or incidence rate per 100 person-years (IR). Results Fungal infections were reported in patients with PsO (IR = 4.0), PsA (IR = 4.1), and axSpA (IR = 2.7). Across indications, most fungal infections were not recurrent and were classified as mild or moderate in severity. There were few severe fungal infections in patients with PsO (IR = 0.1), PsA (IR = 0.0), and axSpA (IR = 0.0). Most fungal infections in patients with PsO, PsA, and axSpA were candidiasis (IR = 1.9, IR = 2.5, IR = 1.4, respectively) and superficial dermatophytosis (IR = 1.5, IR = 1.0, IR = 1.0, respectively). No cases of subcutaneous and systemic mycosis infections were reported. The proportions of patients with PsO, PsA, and axSpA who received a topical vs systemic anti-fungal medication were 53.6% vs 1.1%, 47.8% vs 0.0%, and 45.6% vs 3.5%, respectively (Table 1). Most fungal infections did not lead to discontinuation of IXE (Table 1). Conclusion Consistent with previously disclosed IXE data, the majority of treatment-emergent fungal infections observed in patients with PsO, PsA, or axSpA treated with IXE were: (i) not recurrent; (ii) mild or moderate in severity, (iii) associated with candidiasis and superficial dermatophytosis, (iv) managed with topical anti-fungal medications or no treatment reported, and (v) not leading to drug discontinuation. Disclosure S. Schwartzman: Corporate appointments; SS reports being a board member of the National Psoriasis Foundation. Consultancies; S. Schwartzman has served as a speaker and/or consultant for AbbVie, Janssen, Eli Lilly and Company, Pfizer, UCB, Myriad, Novartis, Regeneron, Sanofi, Stelexis, Jubilant, Teijin. L. Puig: Corporate appointments; Board member of the International Psoriasis Council. Consultancies; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sandoz, Sanofi, UCB. Honoraria; Boehringer Ingelheim, Janssen, Eli Lilly and Company, Novartis, UCB, travel support from Janssen, Eli Lilly and Company, Pfizer, UCB. Grants/research support; L. Puig reports receiving grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sanofi, UCB. A.D. Cohen: Honoraria; AbbVie, Amgen, Boehringer Ingelheim, Dexcel Pharma; Janssen, Eli Lilly and Company, Neopharm, Novartis, Perrigo, Pfizer, Rafa. Grants/research support; A. D. Cohen has served on advisory board for Samsung, and reports receiving grants from AbbVie, Janssen, Novartis, Pfizer, travel support from AbbVie. S. Khattri: Consultancies; S. Khattri reports being part of Eli Lilly and Company speaker’s bureau, receiving consulting fees and honoraria from Eli Lilly and Company, AbbVie, UCB, Janssen, BI, Regeneron, Leo Pharma. C. Jossart: Shareholder/stock ownership; C. Jossart is a stockholder of Eli Lilly and Company and was an employee of Eli Lilly and Company when this study was conducted. C. Diaz: Shareholder/stock ownership; C. Diaz is employee and stockholder of Eli Lilly and Company. A. Garrelts: Shareholder/stock ownership; A. Garrelts is employee and stockholder of Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D. Zhu is employee and stockholder of Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N. Eberhart is employee and stockholder of Eli Lilly and Company. A. Eleftheriadi: Shareholder/stock ownership; A. Eleftheriadi is employee and stockholder of Eli Lilly and Company. N. Tangsirisap: Shareholder/stock ownership; N. Tangsirisap is employee and stockholder of Eli Lilly and Company. C. Schuster: Shareholder/stock ownership; C. Schuster is an employee and stockholder of Eli Lilly and Company. A.B. Gottlieb: Consultancies; Xbiotech (stock options for an RA project). Honoraria; Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapuetics, Dermavant, Lilly, Janssen, Leo, Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma. Grants/research support; AnaptysBio, Moonlake Immunotherapeutics, Novartis, BMS, and UCB Pharma; all funds go to the Icahn School of Medicine at Mount Sinai. M. Sheesh: Shareholder/stock ownership; MS is a full-time employee and minor share holder of Eli-Lilly and Company.

Adherence, persistence and treatment switching in psoriasis.

Aim: This study aims to investigate drug utilization patterns in the treatment of psoriasis (PsO) from 1 to 5years in a real-life setting with Adalimumab (Ada), Etanercept (Eta), Ustekinumab (Ust), Golimumab (Gol), Ixekizumab (Ixe), Secukinumab (Sec) and Apremilast (Apr). Materials & methods: Data from an observational study were used to calculate adherence using the Proportion of Days Covered (PDC) method and persistence. Results & conclusion: Treatment adherence was found to be good for all the drugs studied across all years of analysis, while persistence was suboptimal, showing a marked decrease from the third year of study onward. In the treatment of PsO, greater attention needs to be paid to treatment persistence.

A Comparative Study on Serum Levels of “Thymic Stromal Lymphopoietin” Between Patients with Psoriasis Vulgaris and Healthy Individuals: A Case-Control Study

Abstract Background: Thymic stromal lymphopoietin (TSLP) is a cytokine initially implicated to be associated with allergic disorders inducing Th2 response. Emerging studies have shown that TSLP is also involved in autoimmune diseases. In psoriasis, TSLP acts in synergy with T cell-derived CD40L to promote the release of IL-23 from dendritic cells. IL-23 is responsible for the inappropriate immune reaction and keratinocyte proliferation in psoriasis. Targeting TSLP could be a novel therapeutic approach in the treatment of psoriasis. Objective: To compare the serum levels of TSLP between patients with psoriasis and healthy individuals. Materials and Methods: A prospective hospital-based case-control study was carried out on 38 patients with psoriasis. The severity of psoriasis was graded into mild, moderate, and severe according to PASI. A total of 30 healthy individuals with matched age and sex were taken as controls. 5 ml of venous blood was collected, centrifuged, and the collected serum was stored at -80°C until quantitative assessment by sandwich enzyme-linked immunosorbent assay (ELISA) technique. Results: TSLP has been found to be significantly elevated in the sera of cases (0.1380178 pg/ml) than in controls (0.1125974 pg/ml). There was also a significant proportionate increase in the mean TSLP with the mean PASI score. Limitations: The sample size was small and we could not follow-up the cases to study the changes in TSLP levels with remission of the lesions. Conclusion: We found that serum TSLP was elevated in psoriasis patients and correlated with disease severity, indicating a possible pathogenetic role.

Burden of impaired sleep and its improvement through topical treatment in psoriasis and atopic dermatitis.

Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2weeks (p<0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r>0.50, p<0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r>0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2weeks of topical treatment.

Combined untargeted metabolomics and network pharmacology approaches to reveal the therapeutic role of withanolide B in psoriasis

Psoriasis is a refractory inflammatory skin disorder in which keratinocyte hyperproliferation is a crucial pathogenic factor. Up to now, it is commonly acknowledged that psoriasis has a tight connection with metabolic disorders. Withanolides from Datura metel L. (DML) have been proved to possess anti-inflammatory and anti-proliferative properties in multiple diseases including psoriasis. Withanolide B (WB) is one of the abundant molecular components in DML. However, existing experimental studies regarding the potential effects and mechanisms of WB on psoriasis still remain lacking. Present study aimed to integrate network pharmacology and untargeted metabolomics strategies to investigate the therapeutic effects and mechanisms of WB on metabolic disorders in psoriasis. In our study, we observed that WB might effectively improve the symptoms of psoriasis and alleviate the epidermal hyperplasia in imiquimod (IMQ)-induced psoriasis-like mice. Both network pharmacology and untargeted metabolomics results suggested that arachidonic acid metabolism and arginine and proline metabolism pathways were linked to the treatment of psoriasis with WB. Meanwhile, we also found that WB may affect the expression of regulated enzymes 5-lipoxygenase (5-LOX), 12-LOX, ornithine decarboxylase 1 (ODC1) and arginase 1 (ARG1) in the arachidonic acid metabolism and arginine and proline metabolism pathways. In summary, this paper showed the potential metabolic mechanisms of WB against psoriasis and suggested that WB would have greater potential in psoriasis treatment.