Title: Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis [ID3960]
Funder: Department of Health and Social Care

Abstract: Atopic dermatitis (AD), which is also known as eczema or atopic eczema, is a condition that affects the skin. AD is one of the most common skin disorders in children, with symptoms usually showing before the age of 5 years. But AD can also develop in adulthood. People with AD have dry, red (inflamed) skin that is also extremely itchy (pruritus). Oozing, weeping sores can occur in more severe forms of AD. There is no cure for AD, and the aim of treatment at first is to provide symptom relief and then to control symptoms in the longer term. Mild cases of AD, which most people have, are treated by General Practitioners (GPs). Treatment starts with ointments that are applied to the skin, such as emollients (a cream or ointment that soothes the skin), and gels. Those with more severe AD are likely to need stronger therapies and are usually dealt with by doctors who specialise in treating skin disorders. Severe forms of AD might be treated with phototherapy (exposure to fluorescent light bulbs) or, more often, with systemic treatments, which are drugs that spread throughout the body to target the processes within the body that are causing the inflammation of the skin. Ciclosporin A (CsA) is often the first systemic therapy given. If AD does not get better with CsA, options available in the National Health Service (NHS) after CsA are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for AD but have not been assessed for use in the NHS are abrocitinib, tralokinumab and upadacitinib._x000D_ _x000D_ The aim of this project is to review abrocitinib, tralokinumab and upadacitinib for the treatment of moderate to severe AD in a multiple technology appraisal (MTA). The medical benefits and risks associated with the three treatments will be assessed and compared with each other and against the available standard treatments for AD. In addition, this project will assess whether abrocitinib, tralokinumab and upadacitinib are likely to be considered good value for money for the NHS.

Lay abstract: Atopic dermatitis (AD), often referred to as atopic eczema, is a chronic relapsing inflammatory skin condition.1 One of the most common skin disorders in children, AD typically manifests before the age of 5 years, but can develop at any age. AD is characterized by dry, inflamed skin accompanied by intense itchiness (pruritus). Oozing, weeping lesions can occur in more severe forms of the condition. Scratching constantly due to pruritus leads to sleep disturbance is considered an important factor in the transition of the classification of AD from acute to chronic disease. Bleeding and splitting of the skin, increased prevalence of skin infection are also hallmark features of AD in most people with xerosis (dry skin).1 One in five children and one in ten adults in the UK are estimated to have AD,2, 3 with about 18% of cases of childhood AD categorised as moderate and 2% as severe.3 Of adults with AD, it has been reported that 5% of cases are severe.4 Of the people who need treatment for AD, 7% are estimated to have moderate to severe disease, and, 27% of those receiving treatment will require systemic therapy to elicit sufficient symptom relief.5, 6 Due to repeated episodes of skin infections, extensive antibiotic prescriptions are common among AD patients. As well as physical symptoms, many children and adults experience sleeplessness, anxiety, depression and other mental health problems related to their AD.2 Common co-morbidities are food allergies, allergic rhinitis and allergic asthma._x000D_ _x000D_ AD is currently uncurable, and the goal of treatment is to improve symptoms and achieve long-term disease control. Those with mild AD, who form the majority of cases, are predominantly managed in primary care.7 Guidance for general practitioners (GPs) outlines a step-by-step approach to disease management for a person presenting with AD, starting with preparation of an individualised management plan.7 Initial treatment focuses on topical therapy with emollients and moisturisers, which are the mainstay of therapy but their effectiveness is reliant on the patient applying the emollient as per the recommendations, which can be challenging. For those with mild AD, to effect relief of dry skin, regular use of moisturisers and/or emollients is usually effective in controlling symptoms. Additionally, advice is given on identifying and controlling specific triggers of flare (a worsening of symptoms), for example, overuse of irritants including shampoo and detergents. Cigarette smoke has also been discussed as a trigger factor. Children and adolescents typically receive the same treatments as adults._x000D_ _x000D_ For someone presenting to primary care with a flare, initial treatment is typically a topical corticosteroid (TCS) to suppress inflammation, if this is an acceptable treatment option to the patient. TCSs can be prescribed in different strengths, depending on the severity of disease and the areas of skin affected.8 The topical immunomodulators tacrolimus and pimecrolimus, both of which are calcineurin inhibitors, are additional treatment options in primary care for those patients whose preference is not to use a TCS.7 Topical immunomodulators are also an option for AD affecting areas for which TCSs are not recommended, for example, the eyelids and peri-orbital skin, and for when there are signs of skin atrophy. _x000D_ _x000D_ Those with moderate to severe AD that only partially responds to treatment, and those presenting with severe disease, are referred to secondary care for more specialised therapy, where phototherapy is frequently the first treatment option. If phototherapy is unsuccessful, subsequent treatment typically on systemic therapies such as ciclosporin A (CsA), methotrexate, dupilumab and, more recently, baricitinib. The three treatments that are the focus of the project — abrocitinib, tralokinumab and upadacitinib — are systemic therapies that are potential additions to the treatments for AD currently available to the NHS. The purpose of the project outlined here is to assess the clinical and cost-effectiveness of abrocitinib, tralokinumab and upadacitinib for treating moderate to severe AD compared with current treatments used in England. None of abrocitinib, tralokinumab and upadacitinib has a marketing authorisation in place for treatment of AD in the UK at the time of drafting of the protocol. Should the marketing authorisations become available during the timeframe of the project, the individual treatments will be incorporated into analyses within their respective marketing authorisation.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: SKIN