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Celiac disease is a multifactorial, inflammatory disorder initiated and sustained by the ingestion of gluten. Occurring across a broad population, the intestinal and extraintestinal manifestations of celiac disease are variable in severity and may be nonspecific in presentation. Given that environmental, genetic, and immune factors involved in the pathogenesis of celiac disease that the digestive tract and skin share many characteristics, and with a prevalence of 0.5–1% in most populations, it is reasonable to consider varying presentations of skin conditions that are linked with celiac disease. The association between celiac disease and skin conditions has been discussed earlier, but new studies have emerged suggesting cutaneous involvement in addition to dermatitis herpetiformis. We review the current literature identifying the relationship and potential mechanisms between celiac disease and various skin conditions. [ABSTRACT FROM AUTHOR]

Real‐world and long‐term data on biologic treatment changes – including switching, discontinuation, dose escalation, and interval change (both increasing and decreasing) – are required to understand treatment patterns for psoriasis (PsO) in Canada. The study objectives were to evaluate the time to first biologic treatment change and to document these changes in Canadian patients with moderate‐to‐severe chronic plaque PsO. Charts from 13 Canadian sites were queried retrospectively (2005–2019); a period covering all biologic classes commonly used for PsO in Canada. Included were patients diagnosed with, and currently using biologics for, moderate‐to‐severe chronic plaque PsO. Time to first treatment change, nature of treatment change, number of lines of treatment, proportion of patients on each drug, and drug survival were collected. Based on 1149 medical charts, adalimumab had the longest time to first treatment change (49.3 months; 95% confidence interval, 37.4–67.4). Approximately half of the patients had a treatment change, and nearly 75% of these changes were either an interval change or a biologic switch. Lack of efficacy was the most prevalent primary reason for biologic switch (67.3%), whereas 6.7% of patients switched due to adverse events. Drug survival for etanercept and infliximab was approximately twice as long for patients who had dose optimization (i.e., dose escalation or interval change) than patients without dose optimization. The survival curve of adalimumab was similar to the one of ustekinumab after 48 months of treatment, showing approximately 60% of patients remaining on treatment after 132 months, with or without dose optimization. Assessing treatment patterns of all commonly used biologics for moderate‐to‐severe chronic plaque PsO in Canada between 2005 and 2019 showed that approximately half of the patients required a treatment change (mainly interval change or biologic switch) while the other half remained on treatment. [ABSTRACT FROM AUTHOR]

The effects of consuming a soy protein isolate beverage powder (60 g/d for 28 d) vs. a casein supplement was evaluated in 20 male subjects who were randomly allocated into the two groups. A dramatic rise in plasma isoflavone concentrations was observed after supplementation in the soy protein group, the levels reaching 907 [+ or -] 245 nmol/L for genistein (a 110-fold increase) and 498 [+ or -] 102 nmol/L for daidzein (a 150-fold increase) as measured by isotope dilution gas chromatography - mass spectrometry. These concentrations are higher than previously reported for the plasma of Japanese subjects consuming a traditional diet (276 nmol/L and 107 nmol/L, respectively). No significant differences in collagen- or 9, 11-dideoxy-11[Alpha], 9[Alpha]-epoxymethanoprostaglandin [F.sub.2[Alpha]] (U46619)-induced platelet aggregation were observed in platelet-rich plasma from the two groups; the increase in plasma isoflavonoids from soy protein supplementation is not sufficient to significantly inhibit platelet aggregation ex vivo. Similarly, plasma total and HDL-cholesterol were not affected by protein supplementation, possibly because the men were normocholesterolemic at entry. Analysis of plasma phospholipid polyunsaturated fatty acid composition showed no differences between soy protein and casein supplementation. Previous investigations reported a significant alteration in fatty acid status in animals fed soy protein relative to those fed casein. The present studies indicate that although soy protein supplementation to a typical Western diet can increase plasma concentrations of isoflavones, this may not necessarily be sufficient to counter heart disease risk factors such as high plasma cholesterol and platelet aggregation. J. Nutr. 126: 2000-2006, 1996. INDEXING KEY WORDS: humans; soy protein; isoflavones; platelet; plasma cholesterol

In VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244), guselkumab, an interleukin-23 blocker, was safe and effective in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic (n = 117) or non-Hispanic (n = 1686) were randomized to guselkumab, placebo, or adalimumab. Efficacy assessments included Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). At week 16, treatment differences for guselkumab versus placebo in the Hispanic and non-Hispanic populations were 67.4 (95% confidence interval 50.4, 84.4) and 77.2 (73.5, 80.8) percentage points for IGA 0/1 and 59.2 (41.9, 76.4) and 69.2 (65.7, 72.7) percentage points for PASI 90, respectively. Treatment differences for guselkumab versus adalimumab were 25.9 (6.5, 45.3) and 17.5 (12.8, 22.3) percentage points for IGA 0/1 and 21.4 (–0.1, 42.9) and 23.5 (18.2, 28.9) percentage points for PASI 90, respectively. Week 24 results were similar. Adverse event frequency was greater in adalimumab- versus guselkumab-treated patients in the Hispanic population only through weeks 16 and 28. In both populations, DLQI 0/1 responses were greater in guselkumab-treated versus placebo- and adalimumab-treated patients at week 16 and versus adalimumab-treated patients at week 24. Guselkumab safety and efficacy were consistent between Hispanic and non-Hispanic populations. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic skin disease, characterized by widespread pustules and erythema, often accompanied with systemic signs and symptoms. GPP flares occur episodically but may be protracted. Left untreated, GPP can be life‐threatening. Despite being first reported over 100 years ago, definitions and diagnostic criteria for GPP have been inconsistent and varied due, in part, to its rarity and a limited understanding of its pathogenesis. As such, many patients with GPP face delays in diagnosis and subsequent treatment. This manuscript aims to increase the recognition of GPP and provide foundational considerations to aid in the definition and diagnosis of this disease. [ABSTRACT FROM AUTHOR]

Dermatology, TYK2 inhibitor, deucravacitinib, phase 3, psoriasis, BMS-986165, plaque psoriasis, JAK inhibitor, tyrosine kinase 2 2021; S0190-9622(21)02017-X. •• This is a key article in understanding the role of TYK2 in the pathophysiology of plaque psoriasis and how targeted therapies can play a significant role in the management of psoriasis patients. Keywords: TYK2 inhibitor; deucravacitinib; phase 3; dermatology; BMS-986165; psoriasis; plaque psoriasis; JAK inhibitor; tyrosine kinase 2 EN TYK2 inhibitor deucravacitinib phase 3 dermatology BMS-986165 psoriasis plaque psoriasis JAK inhibitor tyrosine kinase 2 185 187 3 03/22/22 20220301 NES 220301 Psoriasis is a common immune-mediated inflammatory disease affecting approximately 2% of individuals living in Western countries. [Extracted from the article]

Oral abrocitinib 200 and 100 mg once daily provided short-term efficacy in a dose-dependent manner over 12 or 16 weeks in various age groups of patients with moderate-to-severe atopic dermatitis (AD). This study aims to evaluate the long-term efficacy of abrocitinib treatment for up to 96 weeks in adult patients with moderate-to-severe AD who enrolled in JADE EXTEND (NCT03422822). This planned interim analysis included adult patients from the JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470) and DARE (NCT04345367) who subsequently enrolled into the ongoing phase 3 extension trial JADE EXTEND (data cutoff: September 25, 2021). Patients who were randomly assigned to abrocitinib 200 or 100 mg once daily in the qualifying trials continued to receive the same dose in JADE EXTEND with blinding maintained; those who received placebo were randomly assigned to abrocitinib 200 or 100 mg. All patients from JADE DARE received a known dose of abrocitinib 200 mg in JADE EXTEND. Patients previously randomly assigned to dupilumab in JADE DARE or JADE COMPARE were excluded from this analysis. Patients were grouped for analysis by age (18–50 years; >50 years) recorded at the screening visit of the respective qualifying trial. Assessments included the proportion of patients who achieved Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline, ≥75% and ≥90% improvement from baseline on the Eczema Area and Severity Index (EASI-75 and EASI-90), a score of <2 or a ≥4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS 0/1 or PP-NRS4), and a score of <2 on the Dermatology Life Quality Index (DLQI 0/1). Data (as observed values) were evaluated up to 96 weeks of abrocitinib treatment. A total of 1309 patients [18–50 years (n = 1046); >50 years (n = 263)] were analysed. At Week 16 of abrocitinib treatment, patients achieved improvements with abrocitinib 200 or 100 mg in a dose-dependent manner in both age groups for IGA 0/1 [18–50 years, 55% (abrocitinib 200 mg)/34% (abrocitinib 100 mg); >50 years, 56%/38%], EASI-75 (79%/61%; 76%/69%) and PP-NRS4 (70%/51%; 76%/61%). Similar dose-dependent responses in both age groups were observed for the high-threshold clinical, patient-reported and health-related quality of life (HRQoL) endpoints of EASI-90 [18–50 years, 54% (abrocitinib 200 mg)/33% (abrocitinib 100 mg); >50 years, 59%/40%], PP-NRS 0/1 (35%/25%; 54%/30%) and DLQI 0/1 (38%/23%; 47%/24%). Regardless of age and dose, substantial proportions of patients were observed with responses at Weeks 24, 48 and 96 of abrocitinib treatment. At Week 96, dose-dependent responses remained for the younger subgroup of patients (including for high-threshold responses). For the older subgroup, responses were less clearly dose-dependent from Week 48. At Week 96, responder proportions were as follows: for IGA 0/1: 18–50 years, 55% (abrocitinib 200 mg)/44% (abrocitinib 100 mg); >50 years, 58%/51%; for EASI-75: 85%/73%, 89%/86%; for PP-NRS4: 66%/54%; 80%/79%; and for the high-threshold endpoints of EASI-90: 58%/45%; 73%/58%; for PP-NRS 0/1: 38%/26%; 44%/54%; and for DLQI 0/1: 41%/32%; 48%/51%. Regardless of age, substantial proportions of adults achieved clinical and patient-reported endpoints (IGA 0/1, EASI-75 or PP-NRS4) after short-term treatment with either abrocitinib dose. Similar trends were observed for high-threshold clinical, patient-reported and HRQoL endpoints (EASI-90, PP-NRS 0/1 or DLQI 0/1). Dose-dependent efficacy was observed short-term regardless of age, and up to 96 weeks in patients aged 18–50 years. Responder proportions of patients aged >50 years were less clearly dose-dependent from Week 48 of abrocitinib treatment. These findings may be informative for patients and healthcare providers when making treatment decisions. Further data from the ongoing JADE EXTEND trial may provide greater precision for long-term efficacy estimates. [ABSTRACT FROM AUTHOR]

Adherence to topical treatment for a variety of chronic skin conditions, such as psoriasis, acne, and atopic dermatitis, is known to be very poor. A number of factors contribute to this phenomenon, including lack of treatment efficacy and patient concerns regarding side effects, among others. At the forefront of barriers facing optimal patient adherence to topical treatment is choosing the ideal topical vehicle formulation. Medical professionals have demonstrated a lack of understanding with respect to the composition and nomenclature of the various topical formulations. In this review, we clarify the properties and definitions of the following topical formulations: ointments, creams, lotions, topical solutions, topical suspensions, gels, foams, and sprays. We also provide suggested areas of application for the aforementioned formulations and a succinct, patient-geared summary of their advantages and disadvantages. This review hopes to deliver a clear and concise practical summary of the most commonly encountered topical formulations for the treatment of cutaneous disease for medical professionals. This will allow clinicians to provide their patients with accurate information to facilitate informed choice of topical formulation, which may serve to improve treatment adherence. [ABSTRACT FROM AUTHOR]

Background: Biologics have transformed the management of moderate to severe psoriasis. The persistency of biologics lacks real-world data. Objectives: To quantify drug survival of infliximab (IFX), adalimumab (ADA), etanercept (ETA), and ustekinumab (UST) and to identify potential factors affecting drug survival. Methods: An observational, retrospective 2-centre study consisting of 906 patients from private practices in Ontario between July 2003 and June 13, 2016, was conducted, including patients with plaque psoriasis receiving commercial treatment with ADA, ETA, IFX, and UST. Paper and electronic records of each patient were reviewed. Results: Median survival times for UST, IFX, ADA, and ETA were respectively, in months, 68, 23, 33, and 28. Female sex was determined to be a statistically significant positive predictor of drug survival. Our study was consistent with the literature in that UST had the highest survival rate compared to the other biologics, and the shape of our drug survival curve suggested that loss of drug efficacy is a stochastic occurrence. Compared to other studies, our data exhibited lower survival rates at various time points for all the biologics studied, and female sex did not predict drug survival in other studies. We also investigated potential reasons for differences in biologic survival times between different practices; the main differentiator was drug dosage, as higher dosages were associated with greater survival. Conclusion: UST has a higher drug survival rate than ADA, ETA, and IFX, as observed in other studies. When practice patterns are compared, dosage difference is the main factor that may cause differing survival rates. [ABSTRACT FROM AUTHOR]