0
selected
-
1.
Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.
Simpson, EL, Silverberg, JI, Nosbaum, A, Winthrop, KL, Guttman-Yassky, E, Hoffmeister, KM, Egeberg, A, Valdez, H, Zhang, M, Farooqui, SA, et al
American journal of clinical dermatology. 2021;(5):693-707
-
-
Free full text
-
Abstract
BACKGROUND Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.
-
2.
Gene expression of desaturase (FADS1 and FADS2) and Elongase (ELOVL5) enzymes in peripheral blood: association with polyunsaturated fatty acid levels and atopic eczema in 4-year-old children.
Chisaguano, AM, Montes, R, Pérez-Berezo, T, Castellote, AI, Guerendiain, M, Bustamante, M, Morales, E, García-Esteban, R, Sunyer, J, Franch, A, et al
PloS one. 2013;(10):e78245
Abstract
BACKGROUND It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. METHODS AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson's rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. RESULTS Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. CONCLUSIONS AND SIGNIFICANCE Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children.
-
3.
Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial.
Ramírez-Bosca, A, Zapater, P, Betlloch, I, Albero, F, Martínez, A, Díaz-Alperi, J, Horga, JF, ,
Actas dermo-sifiliograficas. 2012;(7):599-607
Abstract
INTRODUCTION Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions. OBJECTIVES The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity. PATIENTS AND METHODS We performed a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis. The patients were randomized to receive, in addition to their standard treatment, Polypodium leucotomos extract or placebo (both in capsule form) for 6 months. The percentage of days on which topical corticosteroids and other atopic dermatitis treatments were used was calculated. RESULTS Use of Polypodium leucotomos extract did not significantly reduce the mean (SD) percentage of days on which topical corticosteroids were used (11% [12%] vs 12% [11%] for placebo). A significant reduction was, however, observed for oral histamine use (median percentage of days, 4.5% in the Polypodium leucotomos group and 13.6% in the placebo group [P= .038]). The percentage of patients who used oral antihistamines was also lower in the Polypodium leucotomos group. CONCLUSION Long-term treatment with Polypodium leucotomos extract has benefits for children and adolescents with atopic dermatitis who require pharmacologic treatment to reduce inflammation and relieve itching.
-
4.
Diet and prevalence of atopic eczema in 6 to 7-year-old schoolchildren in Spain: ISAAC phase III.
Suárez-Varela, MM, Alvarez, LG, Kogan, MD, Ferreira, JC, Martínez Gimeno, A, Aguinaga Ontoso, I, González Díaz, C, Arnedo Pena, A, Domínguez Aurrecoechea, B, Busquets Monge, RM, et al
Journal of investigational allergology & clinical immunology. 2010;(6):469-75
Abstract
BACKGROUND The prevalence of atopic dermatitis (AD), a chronic skin disease, has increased substantially in recent decades, and different factors have been implicated in its etiology. Although dietary habits are being investigated, few conclusive findings have been reported. Nevertheless, increased consumption of polyunsaturated fatty acids (PUFA) and a diet poor in antioxidants have been related to AD. OBJECTIVES The objectives of this study were to investigate the association between AD, the intake of different foods, and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7. METHODS We performed a cross-sectional study with 20 106 schoolchildren aged 6-7 years from 10 different areas of Spain. The participation rate was 76.50%. The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood questionnaire and the criteria of the Spanish Academy of Dermatology. To calculate the Mediterranean diet score, we classified food into 2 groups: Mediterranean food, including fruit, seafood, vegetables, pulses, cereals, pasta, rice, and potatoes; and non-Mediterranean food, including meat, milk, and fast food. RESULTS Milk was negatively associated with AD. Butter and nuts also were negatively associated, although statistical significance was only reached when these foods were consumed 3 or more times a week. CONCLUSIONS We found no association between the Mediterranean diet score and AD and a positive association between AD and obesity.
-
5.
Proliferation of T lymphocytes from atopic dermatitis skin is enhanced upon anti-CD3, reduced upon mitogen and superantigen, and negligible upon tuberculin stimulation.
Volke, A, Bang, K, Thestrup-Pedersen, K
Acta dermato-venereologica. 2000;(6):407-11
Abstract
Knowledge about the nature of lymphocytes infiltrating atopic dermatitis skin is restricted to allergen-specific T cells. We investigated the proliferative capacities of T lymphocytes cultured in an antigen-independent way from biopsies of atopic dermatitis skin. When compared with peripheral blood mononuclear cells (PBMC) from healthy donors or atopic dermatitis patients, the skin-homing lymphocytes proliferated more vigorously in response to stimulation with anti-CD3 antibodies (1 microglml), reflecting their high response capacity. When stimulated with phytohemagglutinin (10 microg/ml) or staphylococcal enterotoxin A (0.1 microg/ml) the skin-homing lymphocytes achieved significantly lower proliferation levels than PBMC. In contrast to normal and atopic PBMC the skin-homing lymphocytes did not respond to tuberculin purified protein derivative (10 microg/ml). In the mixed lymphocyte reaction the skin-homing lymphocytes did not stimulate autologous PBMC to proliferate. We conclude that skin-homing lymphocytes have more pronounced immune deviations than PBMC in patients with atopic dermatitis. They represent a valuable approach for further investigating the pathogenesis of the disease.