Adherence in Atopic Dermatitis.

Atopic dermatitis is a chronic dermatologic condition requiring extended treatment times with topical application of medications. While atopic dermatitis treatments can be highly effective when used as directed, oftentimes patients do not respond as expected, raising concern for nonadherence versus nonresponse. This chapter aims to describe what is currently known about adherence in atopic dermatitis and to discuss strategies to improve adherence in order to improve treatment outcomes. Whether intentional or unintentional, nonadherence to treatment can limit patient outcomes of this disease for a variety of reasons. These include frustration with medication efficacy, inconvenience, and fear of side effects. Other factors include forgetfulness, financial burden of treatment, lack of trust in the physician, dislike of prescribed medication, or lack of understanding of disease or treatment. Several interventions have been studied with the aim of improving adherence in atopic dermatitis-such as educational workshops for patients and caregivers, earlier follow-up visits, and text messages reminders-however, these are often limited by sample size and power. Further research is needed to study both specific patterns of nonadherence in atopic dermatitis, as well as methods to improve them.

Comparative effectiveness of tildrakizumab 200 mg versus tildrakizumab 100 mg in psoriatic patients with high disease burden or above 90 kg of body weight: a 16-week multicenter retrospective study - IL PSO (Italian landscape psoriasis).

PURPOSE: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight. MATERIALS AND METHODS: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. RESULTS: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively. CONCLUSIONS: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Patient preferences for treatment attributes in moderate-to-severe atopic dermatitis: a discrete choice experiment.

Purpose: Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted.Materials and methods: An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes' relative importance (RI).Results: Participants (N = 300; mean age: 45 years; 70% females; 52% systemic therapy experienced) preferred treatments with higher efficacy, lower risk of adverse events (AEs), and less frequent blood tests (p < .05). Treatment attributes, from high to low RI, were itch control (38%), risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%); together, AE attributes accounted for more than half of the RI.Conclusions: Participants preferred AD treatments that maximize itch control while minimizing AE risks, whereas mode of administration had little impact on preferences. Understanding patients' preferences may help improve shared decision-making, potentially leading to enhanced patient satisfaction with treatment, increased engagement, and better clinical outcomes.

Topical Prescription Management.

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.

The Future of Atopic Dermatitis Treatment.

This chapter thoroughly examines recent breakthroughs in atopic dermatitis (AD) treatment, with a primary focus on the medications in the development pipeline. Biologics agents targeting new interleukin receptors like interleukin-31, interleukin-22, and interleukin-2 are discussed along with the novel pathway looking at the OX40-OX40L interaction. Oral agents and small molecule therapies like Janus kinase inhibitors, sphingosine-1-phosphate modulators, and Bruton's tyrosine kinase inhibitors are also discussed along with the various new topical medications. Newly approved topicals like phosphodiesterase-4 and JAK inhibitors are highlighted while also discussing the potential of tapinarof and emerging microbiome-targeted therapies. Beyond conventional approaches, the chapter touches upon unconventional therapies currently being studied. The goal of this chapter is to discuss new advances in AD treatment from medications in the initial stages of development to those nearing FDA approval.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Psoriasis is a skin condition that not only affects the skin but is also linked to issues in the body's fat tissue, which can lead to inflammation and heart problems. The fat tissue in people with psoriasis contains various immune cells, contributing to obesity and insulin resistance. Research has found a strong connection between inflammation in fat tissues and cardiovascular problems in people with psoriasis. Specific substances released by fat tissue, like leptin, resistin, and adiponectin, can impact inflammation and cardiovascular health. Psoriasis patients often show increased levels of these substances. Treatment for psoriasis may influence cardiovascular health. Some studies suggest that certain medications, like methotrexate or TNF inhibitors, may lower the risk of heart events. However, there are also concerns about potential adverse effects, and further research is needed to fully understand how psoriasis treatments affect cardiovascular outcomes. To manage the cardiovascular risks associated with psoriasis, regular screening for heart-related issues is recommended. Lifestyle changes, such as a healthy diet, stress management, and smoking cessation, are also essential. Additionally, specific medications, like statins and metformin, may be beneficial in controlling cardiovascular risk factors in people with psoriasis. Despite advancements in understanding the relationship between psoriasis and cardiovascular health, there are still challenges. Research is ongoing to develop better screening guidelines and treatment strategies. Collaboration between dermatologists, rheumatologists, and cardiologists is crucial to address the complex nature of this condition and its impact on the heart.

Comparative analysis of persistence and remission with guselkumab versus secukinumab and ixekizumab in the United States.

Purpose: Real-world data comparing long-term performance of interleukin (IL)-23 and IL-17 inhibitors in psoriasis are limited. This study compared treatment persistence and remission among patients initiating guselkumab versus IL-17 inhibitors.Methods: Adults with psoriasis initiating guselkumab, secukinumab, or ixekizumab treatment (index date) were identified from Merative™ MarketScan® Research Databases (01/01/2016-10/31/2021). Persistence was defined as no index biologic supply gaps of twice the labeled maintenance dosing interval. Remission was defined using an exploratory approach as index biologic discontinuation for ≥6 months without psoriasis-related inpatient admissions and treatments.Results: There were 3516 and 6066 patients in the guselkumab versus secukinumab comparison, and 3805 and 4674 patients in guselkumab versus ixekizumab comparison. At 18 months, the guselkumab cohort demonstrated about twice the persistence rate as secukinumab (hazard ratio [HR] = 2.15; p < 0.001) and ixekizumab cohorts (HR = 1.77; p < 0.001). At 6 months after index biologic discontinuation, the guselkumab cohort was 31% and 40% more likely to achieve remission than secukinumab (rate ratio [RR] = 1.31; p < 0.001) and ixekizumab cohorts (RR = 1.40; p < 0.001).Conclusions: Guselkumab was associated with greater persistence and likelihood of remission than IL-17 inhibitors, indicating greater disease control and modification potential.

Isotretinoin's Effect on Fasting Lipid Profile in Acne Patients.

OBJECTIVE: To determine the isotretinoin's effect on fasting lipid profile in patients with acne. STUDY DESIGN: Observational study. Place and Duration of the Study: Outpatient Department of Dermatology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan, from 22nd June to 21st December 2022. METHODOLOGY: Patients of clinically moderate and severe acne were selected and prescribed a dose of 0.5mg /kg cap isotretinoin for 6 months. They were advised to get a fasting lipid profile at the baseline and then after two months of isotretinoin therapy. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grading system and Adult Treatment Panel III were used for the grading of abnormalities. McNemar Bowker test was used to assess the difference in variables [serum triglycerides (TGs), cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL)] at the baseline and after 2 months follow-up. RESULTS: A total of 214 patients were evaluated. After 2 months of isotretinoin therapy, TGs and cholesterol levels were elevated to higher grade in 2% of the patients. Likewise in 1% of patients, LDL levels rised to higher grade. Moreover, HDL levels declined to lower grade in 2% of the patients taking isotretinoin. CONCLUSION: Insignificant alterations in the various serum lipid parameters were observed in acne patients during isotretinoin therapy. It is advisable to obtain a baseline fasting lipid profile in all acne patients on isotretinoin and repeated in those with baseline abnormal levels and in patients with a clinical sign of metabolic syndrome and a family history of dyslipidemias. KEY WORDS: Acne, Hyperlipidemias, Isotretinoin, Laboratory monitoring.

Oral methotrexate in the treatment of Hailey‒Hailey disease: a case report.

Hailey‒Hailey disease is a rare chronic autosomal-dominant blistering disease characterized by erosions, fissures, and vegetations occurring in intertriginous regions. To date, there is no specific treatment and there are no therapeutic guidelines, which makes management of the disease challenging. We present the case of a 43-year-old man unsuccessfully treated for Hailey‒Hailey disease with topical and systemic corticosteroids, antibiotics, and surgical debridement. At presentation he had erosions, vegetations, and infection in the axillae and groin. We introduced oral methotrexate, 10 mg weekly, and complete remission was achieved in 3 weeks. After 8 weeks, we decided to discontinue methotrexate due to lesion absence. Over 3 years of follow-up, mild flares were effectively managed with topical miconazole or mild steroid creams. We conclude that oral methotrexate is safe and effective for achieving long-term remission in Hailey‒Hailey disease.

American Academy of Dermatology Guidelines for Managing Atopic Dermatitis.

The American Academy of Dermatology first published a series of guidelines for diagnosing and managing atopic dermatitis in 2014. Twelve clinicians were selected to review, grade, and offer clinical insight on available data regarding the clinical features, symptomology, pathophysiology, education, treatment, and emerging clinical studies on atopic dermatitis (AD). Based on these findings, the AAD released a guideline to streamline information on atopic dermatitis for physicians, recommending using clinical evidence to diagnose and first treating with nonpharmacologic therapies to restore the natural skin barrier. Topical pharmacologic therapies were recommended for improving pruritus and inflammation and newer systemic agents for clinically relevant moderate-to-severe cases. Evidence-based practices were emphasized in comparison to those that lacked therapeutic data. To highlight the emerging evidence and pharmacologic breakthroughs in atopic dermatitis, the AAD produced an updated set of guidelines educating physicians on new agents and their role in treatment. This chapter reviews the AAD guidelines as a tool for managing atopic dermatitis and staying up to date on disease advancements.

Clinical course and disease burden of patients with generalized pustular psoriasis in Portugal: a multicenter retrospective cohort study.

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. METHODS: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. RESULTS: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. CONCLUSIONS: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.

Rosacea in Older Adults and Pharmacologic Treatments.

Rosacea is a chronic inflammatory skin condition that is often more severe in older patients. The main clinical features are erythema, telangiectasia, and inflammatory lesions of the face. The pathogenesis of this condition is not fully understood but certainly multifaceted. Immune and inflammatory dysregulation, genetics, neurogenic dysregulation, microbiome dysbiosis, and systemic disease have all been implicated in rosacea pathogenesis. As we better understand the various pathways that lead to rosacea, we acknowledge that the different symptoms may have unique underlying triggers and mechanisms. Aging also impacts rosacea diagnosis and treatment. Older adults have more severe rosacea symptoms while also having more sensitive and fragile skin than younger patients; therefore, rosacea treatments for older patients require a balance between delivering adequate potency while also minimizing skin irritation and other adverse effects. Until recently, rosacea diagnoses were based on concrete subtypes that did not necessarily capture each patient's manifestation of rosacea. There is now an emphasis on more personalized phenotype-based diagnoses and treatments, which allows for more emphasis on treating individual symptoms and accounting for the unique characteristics of older patients. Centrofacial erythema is best treated with brimonidine and oxymetazoline, while phymatous change and telangiectasia are best treated with surgery and laser ablation. Treatment for rosacea papules and pustules ranges from topicals, such as azelaic acid, ivermectin, metronidazole, minocycline, and encapsulated benzoyl peroxide, to systemics, such as doxycycline and isotretinoin. It is important to understand these treatments in relation to adverse effects and drug interactions that may specifically arise in older populations to provide optimal care. As we advance in understanding rosacea's pathogenesis and adopt personalized phenotype-based approaches, optimizing care for older patients becomes crucial. Continued research into novel treatments is essential to address their unique needs.

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.

Successful treatment of recalcitrant generalized pustular psoriasis of pregnancy with spesolimab.

Generalized pustular psoriasis (GPP) in pregnancy can lead to severe complications for both mother and fetus. The treatment of this disease is challenging, especially in recalcitrant and severe cases. Until present, there are no evidence-based guidelines for the treatment of GPP in pregnancy. Spesolimab, a human monoclonal antibody against the IL-36 receptor, has recently attracted attention as a new therapy for GPP flare. This biologic provides rapid and sustained control of symptoms of GPP flare, although its use in pregnant women has not been reported to date. Here, we report a pregnant woman with refractory GPP who did not respond well to systemic steroids. Administration of spesolimab resulted in complete control of the disease and the birth of a healthy baby. Our case demonstrates that IL-36RN inhibitors are a potentially effective and safe treatment option for GPP in pregnancy.

Effectiveness of secukinumab in patients with psoriasis and psoriatic arthritis in a Saudi real-world setting.

INTRODUCTION: Psoriasis (PsO) is an immune-mediated chronic inflammatory disease that results in severe outcomes that impact the patient's quality of life and work productivity. We investigated the effectiveness of secukinumab in patients with chronic plaque psoriasis and psoriatic arthritis (PsA) over a 12-month period. METHODS: This was a longitudinal, retrospective study of the medical records of 81 patients with psoriasis and/or psoriatic arthritis who had been treated with secukinumab for at least 12 weeks. RESULTS: The Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) percentage, and Dermatology Quality of Life Index (DLQI) among patients with PsO and PsO-PsA showed a statistically significant decrease from baseline over 12 months by approximately 9.86, 19.3%, and 9.7, respectively (p values < 0.001 for each). Moreover, there was a statistically significant decrease in the overall Disease Activity in Psoriatic Arthritis score (DAPSA) by approximately 22.35 from baseline over 12 months of treatment (p < 0.001). Considering the patients who started secukinumab 12 months or more prior to the study cutoff date, the 12-month retention rate was 85%. CONCLUSION: In a Saudi real-world setting, secukinumab proved to be an efficient medication with high efficacy and retention rates.