Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Bimekizumab in psoriasis: a monocentric study evaluating short- and mid-term effectiveness and safety profile in a real-world setting.

INTRODUCTION: Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to be responsible for its high efficacy in treating chronic plaque psoriasis with rapid onset of action in Randomized Controlled Trials (RCTs). Concerning safety, oral candidiasis was one of the most common drug-related adverse events, commonly mild-to-moderate in severity. Although data from RCTs supporting this efficacy and safety profile of bimekizumab is numerous, results from the real-world setting concerning short- and mid-term treatment effectiveness and safety profile are limited. MATERIALS AND METHODS: An observational, retrospective, monocentric study was conducted at the Psoriasis Outpatient Unit of "A. Sygros" Hospital for Skin and Venereal Diseases, in Athens, Greece, which included 61 adult patients with moderate-to-severe skin psoriasis, who received at least one dosage of bimekizumab. RESULTS: At week 4, 65.7% achieved PASI75, 45.7% PASI90, and 32.4% PASI100. After 16 weeks of treatment, 92.3/76.9/66.7% of the patients achieved PASI75/90/100, respectively. Increased BMI, previous treatment with another IL-17 inhibitor, or previous exposure to another biologic did not seem to influence the possibility of achieving PASI90 and PASI100 at week 16 of bimekizumab treatment in this cohort. Six (9.8%) cases of possibly drug-related AEs were reported, from which four incidences of oral candidiasis. CONCLUSION: Our results confirm that this IL17A/F inhibitor is highly effective, with a tolerability profile similar to the one expected from RCTs.

Atopic Dermatitis in Children.

Atopic dermatitis (AD) is extremely common in the pediatric population, and most children with AD will first present to their primary care provider (PCP). The PCP can recognize AD by its clinical features, including itch, a chronic relapsing course, and the characteristic eruption. The cornerstone of AD therapy is dry skin care, typically a short daily bath/shower followed by an emollient applied to all skin. Most children with AD will also require topical medications, such as topical corticosteroids and/or topical nonsteroidal therapies. For children with more severe disease, systemic agents, including several novel therapies, may be required. In managing AD, the clinician must monitor for side effects of medications as well as complications of the AD itself, the most common of which is secondary infection. An understanding of the pathogenesis, treatments, and complications of AD is essential for the PCP, as untreated (or undertreated) AD has a significant impact on the quality of life of affected children and their caregivers. [Pediatr Ann. 2024;53(4):e121-e128.].

The efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial.

BACKGROUND: Vulvar lichen planus (VLP) is a chronic vulvar dermatosis that is difficult to treat and can severely impair quality of life in the absence of adequate treatment. There is a lack of high-quality evidence to direct therapy for VLP. This randomised controlled trial will be the first double-blinded study comparing systemic treatments in VLP and aims to investigate the safety and efficacy of deucravacitinib compared to methotrexate, in patients with VLP who have failed treatment with potent topical corticosteroids. METHODS: A total of 116 women aged ≥ 18 years with moderate to severe VLP (Genital Erosive Lichen Planus (GELP) score ≥ 5) will be recruited. All participants will initially be treated with Diprosone® OV daily, and their outcome will be assessed using the GELP score. At 8 weeks' follow-up, responders (GELP < 5) will be continued on Diprosone® OV. Non-responders (GELP ≥ 5) will be randomised 1:1 in a blinded fashion to receive (i) methotrexate 10 mg weekly + placebo tablet twice daily + folic acid 5 mg weekly or (ii) deucravacitinib 6 mg twice daily + placebo tablet weekly + folic acid 5 mg weekly. The primary endpoint is the difference in the mean change of GELP scores from baseline to week 32 between deucravacitinib and methotrexate groups. DISCUSSION: High-quality evidence guiding the management of women with VLP is lacking. Once completed, this will be the first double-blinded RCT to compare systemic treatments in VLP. The results of this study will provide valuable, high-quality data to guide second-line therapy options for VLP that is recalcitrant to potent topical corticosteroids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000682640. Registered on 26 June 2023.

Discontinuation of Fumaric Acid Esters is Affected by Depressive Symptomatology: A Retrospective Analysis.

Fumaric acid esters (FAEs) remain a widespread therapy option for moderate-to-severe psoriasis. However, drug survival of FAEs is limited by adverse events (AEs) or inadequate treatment response. Depressive disturbances are highly prevalent in psoriasis patients and are hypothesized to be associated with the reporting of AEs and therapy discontinuation. This study's aim was to analyze whether psoriasis patients with comorbid depressive symptomatology are more likely to discontinue treatment with FAEs due to AEs and/or inadequate treatment response. Data were retrospectively extracted from the records of patients starting therapy with FAEs in the Department of Dermatology, University Hospital Essen, Germany between 2017 and 2022, covering the first 52 weeks of treatment. Psoriasis severity and depressive symptomatology, as well as AEs and therapy discontinuation, were analyzed. Psoriasis patients (N = 95, 47.37% female) with depressive symptomatology (42.11%) were more likely to discontinue therapy due to patient-reported AEs, while the total number of reported AEs was not associated with depression. The results support the hypothesis that among psoriasis patients with depressive symptoms, the associated introspection and somatization may result in increased sensitivity for AEs and thus in quicker therapy discontinuation. In these patients, the occurrence of nocebo effects should be minimized, e.g. by special communication techniques.

Clinical pharmacokinetics and pharmacodynamics of oral systemic nonbiologic therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of these therapies establish drug efficacy, toxicity, and optimal dosing to ensure therapeutic drug levels are sustained and adverse effects are minimized. AREAS COVERED: A literature search was performed on PubMed, Google Scholar, and Ovid MEDLINE for PK and PD, efficacy, and safety data regarding oral systemic nonbiologic therapies utilized for moderate-to-severe plaque psoriasis. The findings were organized into sections for each drug: oral acitretin, methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. EXPERT OPINION: Some psoriasis patients may not respond to initial therapy. Ongoing research is evaluating genetic polymorphisms that may predict an improved response to specific medications. However, financial and insurance barriers, as well as limited genetic polymorphisms correlated with treatment response, may restrict the implementation of genetic testing necessary to personalize treatments. How well psoriasis patients adhere to treatment may contribute greatly to variation in response. Therapeutic drug monitoring may help patients adhere to treatment, improve clinical response, and sustain disease control.

Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory cutaneous disease that causes patients psychosocial distress. Topical therapies are utilized for mild-to-moderate disease and for more severe disease in conjunction with systemic therapies. Topical corticosteroids are a cornerstone of treatment for psoriasis, but long-term use can cause stria and cutaneous atrophy and as well as systemic side effects such as topical steroid withdrawal. Non-steroidal topical therapies tend to be safer than topical corticosteroids for long-term use. AREAS COVERED: We conducted a literature review on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of topical therapies for psoriasis. We discuss how the PK and PD characteristics of these therapies inform clinicians on efficacy and toxicity when prescribing for patients. EXPERT OPINION: Topical corticosteroids, used intermittently, are very safe and effective. Long-term, continuous use of topical corticosteroids can cause systemic side effects. Several generic and newly approved non-steroidal options are available, but no head-to-head studies compare the effectiveness of the generics (vitamin D analogs, tacrolimus, pimecrolimus) against the newer therapies (roflumilast, tapinarof). Patients often do not respond to topical therapies due to poor adherence to treatment regimens. For patients resistant to topical treatment, phototherapy or systemic therapy may be an option.

Real-life data over 36 weeks of guselkumab treatment in psoriasis patients: A single-center study from Turkey.

BACKGROUND: Psoriasis is an important health problem responsible for morbidity and workforce loss. In recent years, anti-IL-23 drugs have become essential in psoriasis treatment. OBJECTIVES: This study aimed to investigate the efficacy and safety of guselkumab therapy, recently used in Turkey, by examining real-life data over 36 weeks. METHODS: A total of 39 psoriasis patients (>18 years old) who received guselkumab treatment between December 2021 and December 2022 in the dermatology department of our hospital were included in the study. Patients" ages, sexes, body mass index (BMI), comorbidities, duration of illness, drugs used before guselkumab treatment, clinical response to guselkumab treatment, and side effects, if any, were recorded. Psoriasis Area and Severity Index (PASI) scores at baseline and Weeks 4, 12, 24, and 36 were evaluated, as well as the Dermatology Life Quality Index (DLQI) at the beginning and end of the study. RESULTS: The PASI scores at Weeks 4, 12, 24, and 36 and the DLQI at Week 36 decreased statistically compared with baseline (p < 0.05). The PASI score at baseline and Weeks 4, 24, and 36 did not differ between groups based on IL-17 use (p > 0.05). No significant correlation was observed between BMI, disease duration, and PASI scores at baseline and Weeks 4, 12, 24, and 36. No side effects were observed in any of the patients during treatment. CONCLUSION: This study includes real-life data on the use of guselkumab therapy for psoriasis in the Turkish population. Based on the results, guselkumab is a highly effective and safe treatment.

Efficacy of ceramides and niacinamide-containing moisturizer versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris: A split face, double-blinded, randomized controlled trial.

INTRODUCTION: Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. METHODS: This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. RESULTS: CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. CONCLUSION: Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.

Efficacy and Safety of Dupilumab Treatment with Concomitant Topical Corticosteroids in Children Aged 6 Months to 5 Years with Severe Atopic Dermatitis.

INTRODUCTION: Treatment options for children younger than 6 years with severe atopic dermatitis (AD) are limited, as systemic immunosuppressants may present safety concerns in this young age group. Dupilumab is the first systemic treatment option approved for infants and young children with severe AD in the European Union. This study reports the efficacy and safety of dupilumab with concomitant low-potency corticosteroids in children aged 6 months to 5 years with severe AD. METHODS: This was a pre-specified subgroup analysis of data for patients aged 6 months to 5 years with severe AD at baseline (Investigator's Global Assessment [IGA] = 4) from a randomised, double-blind, placebo-controlled, phase III trial of dupilumab. Patients were randomised to either subcutaneously administered dupilumab (200/300 mg) or matched placebo every 4 weeks, plus low-potency topical corticosteroids for 16 weeks. Co-primary endpoints at week 16 were the proportion of patients with IGA ≤ 1 (clear or almost clear skin) and the proportion of patients with ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Secondary endpoints at week 16 included mean changes in EASI, pruritus, skin pain, sleep loss and quality of life. RESULTS: The analysis included 125 patients (63 receiving dupilumab vs. 62 placebo). At week 16, significantly more patients receiving dupilumab vs. placebo had achieved IGA ≤ 1 (14.3% vs. 1.6%; P = 0.0085) and EASI-75 (46.0% vs. 6.6%; P < 0.0001). Significant improvements with dupilumab were observed in all secondary endpoints, including a least squares mean 48.9% reduction in pruritus. The overall incidence of adverse events (AEs) was similar between the dupilumab and placebo groups (66.7% vs. 73.8%). No dupilumab-related AEs were serious or led to treatment discontinuation. CONCLUSION: Dupilumab significantly improved AD signs, symptoms and quality of life in children aged 6 months to 5 years with severe AD with acceptable safety. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov with ID number NCT03346434, part B.

Atopic dermatitis (AD) is a chronic skin disease that is relatively common in infants and young children worldwide. Severe AD causes skin rashes and intense itch that strongly interfere with sleep quality and normal daily activities, thereby affecting the quality of life of patients and their families. When therapies for AD that are applied to the skin do not work, limited options are available to treat severe AD in children younger than 6 years. In this study, we evaluated the efficacy and safety of dupilumab in children aged 6 months to 5 years with severe AD, recruited from various sites in Europe and North America. Patients received 200 or 300 mg of dupilumab (based on the child's weight) or placebo, together with mild steroids applied to the skin, every 4 weeks for 16 weeks. At the end of treatment, AD severity was greatly improved in patients receiving dupilumab, with 14% of patients achieving almost clear skin. Patients receiving dupilumab also experienced significant improvements in itch intensity, sleep quality, skin pain, and quality of life. Furthermore, dupilumab did not increase the risk of infections. This study demonstrates that dupilumab can be effective at treating severe AD in infants and young children, with important benefits for the quality of life of patients and their families.

Efficacy of a multitargeted, salicylic acid-based dermocosmetic cream compared to benzoyl peroxide 5% in Acne vulgaris: Results from a randomized study.

INTRODUCTION: Acne vulgaris (acne) is characterized by both inflammatory and non-inflammatory lesions. Benzoyl peroxide (BPO) 5% is approved to treat acne but may cause skin irritation and/or contact allergy. OBJECTIVES: To compare the benefit in acne of a multitargeted dermocosmetic cream containing salicylic acid, lipohydroxy acid, niacinamide, 2-oleamido-1,3-octadecanediol, piroctone olamine, zinc, Aqua posae filiformis, and thermal spring water (DC-Eff) to BPO 5% gel. MATERIALS AND METHODS: 150 Caucasian subjects (50% female) aged between 18 and 40 years, with mild to moderate acne according to the GEA (Global Evaluation of Acne) grading system were randomized into two parallel groups (DC-Eff or BPO to be applied twice daily for 56 days). IGA (investigator global assessment), GEA, lesion count, clinical signs and symptoms, and subject assessment were evaluated at baseline, and after 28 and 56 days (D28 and D56) of treatment. RESULTS: The responder analyses of the IGA and GEA scores showed that 62.2% and 47.3%, respectively, in the DC-Eff, compared with 50.0% and 36.5%, respectively, in the BPO, had improved by at least one point at D56. Inflammatory, non-inflammatory, and total lesion counts significantly (p < 0.0001) decreased with both products from baseline, with no between-group difference. Subjects considered that their skin was smoother and that DC-Eff was easy to apply. DC-Eff was better tolerated than BPO. CONCLUSIONS: DC-Eff applied twice daily is as beneficial as BPO in improving mild-to-moderate acne. DC-Eff was better tolerated than BPO and highly appreciated.

The efficacy of a transdermal hydrogel patch containing betamethasone dipropionate for treatment of chronic hand eczema: A single-blind, randomized and controlled trial.

BACKGROUND: Topical corticosteroids under occlusion have been used to enhance the treatment of eczema. However, no study has investigated the efficacy of a steroid-containing transdermal patch for the treatment of chronic hand eczema. METHODS: We conducted a randomized, controlled, assessor-blinded trial to determine the efficacy of a transdermal patch containing betamethasone dipropionate compared to topical betamethasone dipropionate ointment in the treatment of mild to moderate chronic hand eczema. The patients were included and assigned to receive either the transdermal patch once daily at night or the ointment twice daily for a period of 8 weeks. The outcomes were assessed using the Hand Eczema Severity Index (HECSI), Physical Global Assessment (PGA) score, self-reported compliance, level of patient satisfaction, quality of life, and side effects. RESULTS: Fifty-six patients completed this study. At 8 weeks, there was a significant reduction in the HECSI scores in both the transdermal patch and topical ointment groups compared to those measured at baseline (14.61 to 1.86, p < 0.001; 18.46 to 3.43, p < 0.001, respectively) without a statistically significant difference between the two groups. Similarly, the two groups did not show any significant difference in the PGA scores, quality of life and side effects. However, the transdermal patch group reported better compliance and a higher level of patient satisfaction than the topical ointment group. CONCLUSION: The transdermal corticosteroid patch has proven to be a safe and effective treatment, comparable to topical corticosteroids, after 8 weeks of use. Its sustained-release properties, along with once-daily use, can improve patient satisfaction and promote greater adherence to the treatment. TRIAL REGISTRATION: This study was registered with the Thai Clinical Trials Registry (www. CLINICALTRIALS: in.th) under registration number TCTR20220413003.

Racial, ethnic, and biologic sex disparities in outpatient laboratory monitoring of isotretinoin use: a cross-sectional study.

BACKGROUND: Isotretinoin is commonly used for the treatment of acne. Despite high efficacy, isotretinoin has a side effect profile that prompts regular outpatient laboratory monitoring. Emerging evidence suggests clinically significant lab abnormalities are rare. Racial, ethnic, and biologic sex disparities in laboratory monitoring of isotretinoin have yet to be characterized. METHODS: This study explores disparities in laboratory monitoring of patients prescribed isotretinoin, factoring in the COVID-19 pandemic given its impacts on laboratory monitoring. Two populations were evaluated: all patients taking isotretinoin, and patients taking isotretinoin with no metabolic, cardiovascular, hematologic, hepatic, or renal comorbidities. The latter population was included to screen out patients who might receive increased laboratory testing for conditions besides isotretinoin use. RESULTS: Our data reveal that African-American, Asian, and Hispanic patients prescribed isotretinoin were more likely than Caucasian patients to receive orders for outpatient laboratory monitoring. These disparities persisted independent of comorbidities that may prompt additional testing, suggesting that non-Caucasian patients bear an additional testing burden even when their comorbidities were matched to their peers. Disparities persisted in the setting of reduced laboratory monitoring due to the COVID-19 pandemic. CONCLUSIONS: These data reveal that patients of color are more likely to receive outpatient laboratory monitoring for isotretinoin prescriptions. There is an opportunity for testing standardization to improve medication access, decrease burden and costs for patients and the healthcare system, and decrease racial disparities in prescribing and monitoring of isotretinoin. Dermatology clinics may benefit from standard operating procedures outlining for whom regular monitoring is needed.