Title: Topical anti-inflammatory treatments for eczema: a network meta-analysis
Funder: Department of Health and Social Care

Abstract: Aim To improve the lives of people with eczema by systematically reviewing and analysing the best available data on effectiveness and safety of anti-inflammatory treatments applied to the skin. Background Eczema affects up to 20% of young children and 5% of adults and has a significant quality of life impact. Eczema is not currently preventable or curable. The two core treatments for eczema are: (1) moisturisers for dry skin and preventing flare-ups; and (2) anti-inflammatory treatments applied topically (directly to the skin), including corticosteroids and newer treatments such as calcineurin inhibitors. Anti-inflammatory treatments are essential eczema treatments as they control inflammation, which is the process leading to redness and itch. In 2019 the NHS in England spent over &pound;70 million on community prescriptions for 226 different topical anti-inflammatory treatments for managing eczema. Over 50 new products are currently being tested in over 200 ongoing clinical trials of topical eczema treatments. Currently, it is not possible to identify which are the most effective and best-tolerated topical anti-inflammatory treatments because so few direct head-to-head comparisons have been done. A 2016 review found that most clinical trials in this area compare anti-inflammatory treatments to placebo or dummy topical treatments, rather than comparing them with each other. This makes it difficult for doctors and patients to choose between different treatments in clinical practice. Methods We will systematically search for all clinical trials on topical anti-inflammatory treatments for eczema to examine whether treatments differ in terms of effectiveness and recorded side effects. We will combine the information from published eczema treatment trials using network meta-analysis. Network meta-analysis will allow us to compare different treatments, even if they were not directly compared with each other in the original trials, because network meta-analysis includes indirect comparisons between topical anti-inflammatory treatments which have both been compared with a similar placebo or dummy treatment in clinical trials. Potential impact This research will synthesise the best evidence on the most effective and best-tolerated topical anti-inflammatory treatments for eczema, demonstrating the evidence for hidden comparisons for the first time. This will allow more informed decision-making by people with eczema, their carers and healthcare providers, by clarifying the relative benefits and risks of different eczema treatments. This may also improve treatment outcomes by clarifying the benefits and risks of novel, more expensive treatments over established, cheaper treatments. Dissemination We will publish the review within the Cochrane library, and a leading peer-reviewed journal. We will engage with relevant patient, professional, guideline and healthcare provider groups to ensure uptake of our findings into clinical practice. Patient and public involvement This research question was prioritised in a James Lind Alliance Priority Setting Partnership and a Cochrane Skin group prioritisation process, which included patients and the public as well as health professionals. We have incorporated feedback from the Centre of Evidence-Based Dermatology Patient Panel in developing this application. Together with our public contributor co-applicant, they will continue to provide input during delivery and dissemination of the proposed research.

Lay abstract: Aim To improve the lives of people with eczema and their carers, by systematically reviewing the best available evidence on the benefits and possible harms of anti-inflammatory (or flare control) treatments applied to the skin. Background Eczema is an itchy skin condition affecting around 1 in 5 children and 1 in 20 adults. Eczema can have a big impact on people s quality of life and at the moment it cannot be prevented or cured. The two key treatments for eczema are: (1) moisturisers to soothe dry skin and reduce flare-ups; and (2) anti-inflammatory treatments applied topically (directly to the skin) when the skin becomes red and itchy. Topical anti-inflammatory treatments include steroids, newer treatments such as calcineurin inhibitors, as well as over 50 new products being tested. Topical anti-inflammatory treatments are good at calming down flares of eczema, but we don t know which treatments are best, because the research studies don t usually compare anti-inflammatory treatments with each other. Most research studies compare topical anti-inflammatory treatments to a plain cream ( placebo ), which helps us know whether the treatments are better than a plain cream, but doesn t tell us which topical anti-inflammatory treatments work best. Over 200 different topical anti-inflammatory treatments are used in the NHS for treating eczema and not knowing which ones work best can be confusing for people with eczema and their doctors. Methods We will bring together results from all research studies of topical anti-inflammatory eczema treatments, to compare how well they work and how often they cause side effects. We will combine the information from research studies using a technique called network meta-analysis, which allows us to compare different anti-inflammatory treatments with each other, even if research studies have only ever compared them with a plain cream. Combining direct and indirect evidence within a network will give us a clearer picture of which treatments work best. Potential impact We will draw together the best evidence on which topical anti-inflammatory eczema treatments work best and are best tolerated. This will mean people with eczema and their carers can receive clearer and more consistent advice when they are looking for the best eczema treatment. This will lead to more informed treatment decisions and may lead to better controlled eczema. Patient and public involvement This topic was voted as a priority for eczema research in a project involving people affected by eczema and doctors and nurses. The project received advice from people affected by eczema, whose continued involvement will help ensure the results are about what matters most to people affected by eczema. We will send our results to people affected by eczema and to doctors and nurses, to make sure they have an impact on eczema treatment.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: SKIN