470 research outputs found
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Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families.
IntroductionThe impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov ).MethodsIn both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator's Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) (2-15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2-17 years). Established QoL score severity bands provided clinical context.ResultsGreater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: - 4.6 vs. - 3.0; P < 0.001; DLQI: - 5.2 vs. - 3.5; P = 0.015]. At baseline, more than half the patients had a "moderate effect" or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having "small effect" to "no effect", The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: - 3.7 vs. - 2.7; P = 0.003).ConclusionCrisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.Trial registrationAD-301: http://www.clinicaltrials.gov , NCT02118766; AD-302: http://www.clinicaltrials.gov , NCT02118792.FundingAnacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY
Comorbidities of atopic dermatitis—what does the evidence say?
Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD
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Exploring content and psychometric validity of newly developed assessment tools for itch and skin pain in atopic dermatitis.
BackgroundAtopic dermatitis (AD) is a common skin disorder characterized by chronic inflammation, altered skin barrier function, and inflammatory cell skin infiltration that decreases health-related quality of life (HRQoL). The study objective was to understand the patient perspective of AD burden and determine suitable patient-reported outcome (PRO) measures.MethodsThis mixed methods study involved the collection of qualitative and quantitative information from adults (≥ 18 years old) and adolescents (12 - 17 years old) with clinician-confirmed AD regarding their experiences of AD symptoms and its impact on HRQoL. The first part of the study included three stages: in-person concept elicitation (CE) interviews, a 2-week daily electronic diary (eDiary) study, and in-person cognitive debriefing (CD) interviews. An Itch numeric rating scale (NRS) (v1.0) and a Skin Pain NRS (v1.0) evaluation during CD interviews required participants to think about their 'worst' itch and 'worst' skin pain in the past 24 h. Other PRO measures allowed for psychometric testing. The second part of the study involved telephone-depth interviews (TDIs) and qualitative feedback from participants who had not participated in the CD interviews. Qualitative data were thematically analyzed. Psychometric evaluation of NRS measures was performed using eDiary data.ResultsIn the CE interviews, itch and/or itching and skin pain were the most prevalent symptoms consistently discussed by participants. Both NRS measures demonstrated strong psychometric reliability and were applicable across ages with suitable concurrent validity. During the CD interviews, some participants focused their answers on their 'average' itch/itching in the past 24 h, rather than their 'worst' itch. Some participants answered the Skin Pain NRS thinking about general pain or other types of pain, rather than skin pain specifically. Consequently, modifications to both measures addressed these issues and re-tested as paper-and-pen versions in subsequent TDIs. Itch NRS (v2.0) modifications helped participants focus on their worst itching. Most participants preferred Skin Pain NRS v2.0b, which included skin pain descriptors.ConclusionsItching and skin pain are the most important and relevant AD symptoms. The Itch NRS (v2.0) and Skin Pain NRS (v2.0b) appear to be appropriate endpoints for the assessment of itching and skin pain severity for clinical trials with adults and adolescents with AD
IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.
Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus
Durability of Response to Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis After Treatment Discontinuation in a Phase 2b Trial
ntroduction: Multiple clinical trials showed that 12 weeks of abrocitinib monotherapy was safe and effective for the treatment of moderateto-severe atopic dermatitis (AD). The reversibility of pharmacologic activity after abrocitinib discontinuation was not described. Methods: This post hoc analysis used data from a phase 2b study to evaluate maintenance of disease control during a 4-week drug-free follow-up period in patients with moderate-tosevere AD treated with once-daily abrocitinib (200 mg/100 mg) or placebo for 12 weeks. Proportions of patients who achieved and maintained 50% or 75% improvement in Eczema Area and Severity Index (EASI-50/EASI75), an Investigator’s Global Assessment (IGA) score of 0/1, or at least a 4-point improvement in the pruritus numeric rating scale (pruritus NRS4) were determined. Biomarkers of Janus kinase inhibition and AD disease were measured in blood samples. Results: Among week 12 responders to abrocitinib 200 mg, 77.4%, 42.3%, 21.1%, and 42.9% maintained their EASI-50, EASI-75, IGA, and pruritus NRS4 response at week 16; corresponding proportions of week 12 responders maintaining response to abrocitinib 100 mg were 51.9%, 35.0%, 33.3%, and 43.5%, respectively. Four weeks after abrocitinib discontinuation, all AD biomarkers reverted towar
Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus
Background: Nemolizumab targets the IL-31 receptor a subunit
involved in atopic dermatitis (AD) pathogenesis.
Objective: We sought to evaluate a new dosing strategy of
nemolizumab in patients with AD.
Methods: We performed a 24-week, randomized, double-blind,
multicenter study of nemolizumab (10, 30, and 90 mg)
subcutaneous injections every 4 weeks versus placebo, with
topical corticosteroids in adults with moderate-to-severe AD,
severe pruritus, and inadequate control with topical treatment
(n 5 226). The Eczema Area and Severity Index (EASI), the
peak pruritus (PP) numeric rating scale (NRS), and the
Investigator’s Global Assessment (IGA) were assessed. Standard
safety assessments were performed.
Results: Nemolizumab improved EASI, IGA, and/or NRS-itch
scores, with the 30-mg dose being most effective.
Nemolizumab (30 mg) reduced EASI scores versus placebo at
week 24 (268.8% vs 252.1%, P 5 .016); significant
differences were observed by week 8 (P <_ .01). With significant
improvement (P 5 .028) as early as week 4, IGA 0/1 rates
were higher for 30 mg of nemolizumab versus placebo at week
16 (33.3% vs 12.3%, P 5 .008) but not week 24 because of an
increased placebo/topical corticosteroid effect (36.8% vs
21.1%, P 5 .06). PP-NRS scores were improved for 30 mg of
nemolizumab versus placebo at week 16 (268.6% vs 234.3%,
P <.0001) and week 24 (267.3% vs 235.8%, P <.0001), with a
difference by week 1 (P _4-point
decrease) were greater for 30 mg of nemolizumab versus
placebo at week 16 (P <_ .001) and week 24 (P <_ .01).
Nemolizumab was safe and well tolerated. The most common
adverse events were nasopharyngitis and upper respiratory
tract infection.
Conclusions: Nemolizumab resulted in rapid and sustained
improvements in cutaneous signs of inflammation and pruritus
in patients with AD, with maximal efficacy observed at 30 mg.
Nemolizumab had an acceptable safety profile. (J Allergy Clin
Immunol 2020;145:173-82.
Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: results from two phase III, randomized, double-blinded, placebo-controlled trials
Lebrikizumab, a high-affinity IgG-4 monoclonal antibody targeting interleukin (IL)-13, selectively prevents the formation of the IL-13Ra1/IL-4Ra heterodimer receptor signalling complex. Lebrikizumab demonstrated rapid, dose-dependent efficacy and an acceptable safety profile in patients with moderate-to-severe atopic dermatitis (AD) in a phase IIb trial (NCT03443024). Here, we report 16-week efficacy and safety outcomes of lebrikizumab monotherapy in patients with AD from two ongoing 52-week, randomized, double-blinded, placebo-controlled phase III trials – ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Eligible patients with moderate-to-severe AD [adults and adolescents (12–17 years of age, weighing ≥40 kg)] were randomized 2: 1 to subcutaneous lebrikizumab 250 mg or placebo every 2 weeks. Efficacy analyses included proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1, Eczema Area and Severity Index (EASI)-75 and Pruritus Numerical Rating Scale (NRS) ≥ 4-point improvement from baseline (P ≥ 4) at week 16. Nonefficacy-related missing data were imputed by multiple imputation. In ADvocate1, proportions of patients treated with lebrikizumab 250 mg (n = 283) and placebo (n = 141) achieving IGA 0/1 at week 16 were 43.0% and 12.8% (P \u3c 0.001); EASI-75 responses were 59.3% and 16.4% (P \u3c 0.001); P ≥ 4 proportions were 46.3% and 12.7% (P \u3c 0.001), respectively. In ADvocate2 (lebrikizumab, n = 281; placebo, n = 146), corresponding proportions for IGA 0/1 were 33.1% and 10.9% (P \u3c 0.001); EASI-75 responses were 50.8% and 18.2% (P \u3c 0.001); P ≥ 4 proportions were 38.3% and 11.3% (P \u3c 0.001), respectively. The percentage of patients reporting ≥1 TEAE was comparable in ADvocate1 (lebrikizumab, 45.4%; placebo, 51.1%) and ADvocate2 (lebrikizumab 53.0%; placebo 66.2%). Data from two ongoing pivotal phase III trials suggest that lebrikizumab 250 mg Q2W provides an efficacious treatment option with an acceptable safety profile for patients with moderate-to-severe AD
Global Skin Disease Morbidity and Mortality: An Update From the Global Burden of Disease Study 2013.
Importance: Disability secondary to skin conditions is substantial worldwide. The Global Burden of Disease Study 2013 includes estimates of global morbidity and mortality due to skin diseases. Objective: To measure the burden of skin diseases worldwide. Data Sources: For nonfatal estimates, data were found by literature search using PubMed and Google Scholar in English and Spanish for years 1980 through 2013 and by accessing administrative data on hospital inpatient and outpatient episodes. Data for fatal estimates were based on vital registration and verbal autopsy data. Study Selection: Skin disease data were extracted from more than 4000 sources including systematic reviews, surveys, population-based disease registries, hospital inpatient data, outpatient data, cohort studies, and autopsy data. Data metrics included incidence, prevalence, remission, duration, severity, deaths, and mortality risk. Data Extraction and Synthesis: Data were extracted by age, time period, case definitions, and other study characteristics. Data points were modeled with Bayesian meta-regression to generate estimates of morbidity and mortality metrics for skin diseases. All estimates were made with 95% uncertainty intervals. Main Outcomes and Measures: Disability-adjusted life years (DALYs), years lived with disability, and years of life lost from 15 skin conditions in 188 countries. Results: Skin conditions contributed 1.79% to the global burden of disease measured in DALYs from 306 diseases and injuries in 2013. Individual skin diseases varied in size from 0.38% of total burden for dermatitis (atopic, contact, and seborrheic dermatitis), 0.29% for acne vulgaris, 0.19% for psoriasis, 0.19% for urticaria, 0.16% for viral skin diseases, 0.15% for fungal skin diseases, 0.07% for scabies, 0.06% for malignant skin melanoma, 0.05% for pyoderma, 0.04% for cellulitis, 0.03% for keratinocyte carcinoma, 0.03% for decubitus ulcer, and 0.01% for alopecia areata. All other skin and subcutaneous diseases composed 0.12% of total DALYs. Conclusions and Relevance: Skin and subcutaneous diseases were the 18th leading cause of global DALYs in Global Burden of Disease 2013. Excluding mortality, skin diseases were the fourth leading cause of disability worldwide
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