What is the evidence-base for atopic eczema treatments? A summary of published randomised controlled trials

Atopic eczema (AE) is a common chronic inflammatory skin condition. Whilst many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, an NIHR HTA systematic review identified and evaluated existing randomised controlled trials (RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using: MEDLINE, EMBASE, CENTRAL, LILACS, AMED, CINAHL and Cochrane Skin Group Specialised Register (searched to August 31st 2013 (RCTs) and 31st December 2015 (systematic reviews)). Outcome measures included: symptoms, AE severity, quality-of-life, and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to be low risk of bias. When combined with RCTs from the previous review (n= 254), we found ‘reasonable evidence of benefit’ for corticosteroids, calcineurin inhibitors, Atopiclair™, ciclosporin, azathioprine, ultraviolet light and education programmes. Interventions with reasonable evidence of ‘no benefit’ included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic-containing corticosteroids for non-infected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of Eczema Trials (GREAT) Database

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BackgroundComparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling.ObjectivesTo reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE.MethodsProposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey.ResultsA total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined.ConclusionsThis core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers)

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23–24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international group working together to develop a core outcome set (COS) for clinical trials in eczema (synonymous with atopic eczema and atopic dermatitis). HOME is coordinated from the Centre of Evidence Based Dermatology, University of Nottingham, U.K. Participation in HOME is open to anyone with an interest in outcomes for eczema. A COS is the agreed upon minimum set of instruments that should be included in all clinical trials for a particular condition. Use of a COS does not preclude using other instruments; other domains and instruments can also be included to meet the specific requirements of individual trials. COS initiatives are active across many fields of medicine and should enable better synthesis of trial data and reduce selective outcome reporting bias. The HOME initiative follows the best current guidance on developing a COS. Four core domains have been identified: clinician-reported signs; patient-reported symptoms; quality of life; and long-term control. The core outcome measurement instruments for clinician-reported signs and patient-reported symptoms have been established: the Eczema Area and Severity Index (EASI) for measuring clinician reported signs was agreed on at the HOME III meeting, and the Patient-Oriented Eczema Measure (POEM) was chosen to measure patient-reported symptoms at the HOME IV meeting. This is a report from the fifth consensus meeting of the HOME initiative (HOME V), which was held on 12–14 June 2017 in Nantes, France. The local organizers were Sebastien Barbarot and Jean-Francois Stalder of Nantes University Hospital, France

The triangular nasal notch sign in patients with Crohn's disease treated with tumor necrosis factor inhibitors

Tumor necrosis factor (TNF) inhibitors are used to treat a range of chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Some of the cutaneous side effects of these drugs are well documented, such as infections, skin carcinomas, palmoplantar and skinfold pustulosis, psoriasis-like or eczema-like lesions. We are not aware of TNF inhibitor-induced nasal lesions in the literature. We report a case series demonstrating a specific pattern of cicatricial nasal fissure (triangular nasal notch) following nasal dermatitis episodes in patients treated with TNF inhibitors. This article is protected by copyright. All rights reserved

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

Epidemiology of atopic dermatitis in adults: Results from an international survey.

Background:There are gaps in our knowledge of the prevalence of adult atopicdermatitis (AD).Objective:To estimate the prevalence of AD in adults and by disease severity.Methods:This international, cross-sectional, web-based survey was performed inthe United States, Canada, France, Germany, Italy, Spain, United Kingdom, andJapan. Adult members of online respondent panels were sent a questionnaire forAD identification and severity assessment; demographic quotas ensured populationrepresentativeness for each country. A diagnosis of AD required subjects to be posi-tive on the modified UK Working Party/ISAAC criteriaandself-report of ever hav-ing an AD diagnosis by a physician. The proportion of subjects with AD whoreported being treated for their condition was determined and also used to estimateprevalence. Severity scales were Patient-Oriented SCORAD, Patient-OrientatedEczema Measure, and Patient Global Assessment.Results:Among participants by region, the point prevalence of adult AD in the over-all/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% inthe EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vsfemales, and decreased with age. Regional variability was observed within countries.Severity varied by scale and region; however, regardless of the scale or region, propor-tion of subjects reporting severe disease was lower than mild or moderate disease.Conclusions:Prevalence of adult AD ranged from 2.1% to 4.9% across countries.Severe AD represented a small proportion of the overall AD population regardlessof measure or region

The patient-reported disease burden in adults with atopic dermatitis : a cross-sectional study in Europe and Canada

Cross-sectional data on patient burden in adults with atopic dermatitis () from real-world clinical practice are limited. This study compared patient-reported burden associated with adult across severity levels from clinical practices in Canada and Europe. This study included adults (18-65 years) diagnosed with by dermatologists, general practitioners or allergists. Participants categorized as mild (n = 547; 37.3%), moderate (n = 520; 35.4%) or severe (n = 400; 27.3%) based on Investigator's Global Assessment completed a questionnaire that included pruritus and pain numerical rating scales, Patient-Oriented-Scoring of Atopic Dermatitis (PO-SCORAD) itch and sleep visual analogue scales, Dermatology Life Quality Index (), and the Hospital Anxiety and Depression Scale (HADS). Participants were also stratified by inadequate efficacy/intolerance/contraindication to cyclosporine [Cyclo; n = 62 (4 mild, 18 moderate, 40 severe)] and any systemic immunomodulatory agent [; n = 104 (13 mild, 31 moderate, 60 severe)] and compared with the severe group excluding participants identified as Cyclo/. Age was similar across severity groups; the proportion of women was higher in the mild group relative to severe (61.2% vs. 50.5%; P < 0.001). Compared with moderate and mild, participants with severe had more comorbidities, higher itch and pain severity, worse sleep and higher levels of anxiety and depression (all P < 0.001). Mean ± score among participants with severe (16.2 ± 6.9) showed a large effect on quality of life that was higher than those with moderate (10.2 ± 6.3) and mild (5.5 ± 4.9) (both P < 0.001). The burden among Cyclo and subgroups was generally similar to that of participants with severe . Adults with reported a substantial burden across multiple domains that was significantly higher in those with severe disease. The burden among participants in the Cyclo/ subgroups was similar to those with severe

Dupilumab provides rapid and sustained improvement in SCORAD outcomes in adults with moderate-to-severe atopic dermatitis: combined results of four randomized phase 3 trials

Background:Dupilumab, a first-in-class therapy targeting the two key cytokines involved in the persistent underlying inflammatory pathway in atopic dermatitis (AD), is approved for treatment of moderate-to-severe AD in Europe, USA, Japan and several other countries. Objective:To assess dupilumab effects on SCORing Atopic Dermatitis (SCORAD) and component scores (objective and subjective SCORAD) over time in adults with moderate-to-severe AD. Methods:Thispost hocanalysis included 2,444 patients in four placebo-controlled, double-blind, randomized, phase 3 trials. SOLO 1 and 2 (NCT02277743; NCT02277769) evaluated 16 weeks of dupilumab monotherapy against placebo. CAFe (NCT02755649) and CHRONOS (NCT02260986) evaluated dupilumab with concomitant topical corticosteroids (TCS) against TCS alone for 16 and 52 weeks, respectively. Results:2,444 patients randomized to treatment in SOLO 1 and 2 (N = 1,379), CAFe (N = 325) and CHRONOS (N = 740) were analyzed. Dupilumab treatment significantly improved overall SCORAD and individual components as early as Week 1 or 2, with significant and clinically meaningful differences vs. control through end of treatment (p < .0001). These results occurred irrespective of dupilumab regimen, 300 mg subcutaneously weekly or every 2 weeks. Conclusions:In four large phase 3 trials in adults with moderate-to-severe AD, dupilumab treatment with or without concomitant TCS resulted in rapid and sustained improvements in all SCORAD outcomes vs. placebo or TCS alone