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  • Title: Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis.
    Author: Edwards SJ, Karner C, Jhita T, Barton S, Marceniuk G, Yiu ZZN, Wittmann M.
    Journal: Health Technol Assess; 2024 Jan; 28(4):1-113. PubMed ID: 38343072.
    Abstract:
    BACKGROUND: Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus). OBJECTIVES: To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib). DATA SOURCES: Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review. METHODS: A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources. RESULTS: Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost. CONCLUSIONS: The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations. FUTURE WORK AND LIMITATIONS: The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective. STUDY REGISTRATION: This study is registered as PROSPERO CRD42021266219. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information. Atopic dermatitis is one of the most common skin conditions in children but can also develop in adulthood. People with atopic dermatitis have dry, red (inflamed) skin that is also extremely itchy (pruritus). There is no cure for atopic dermatitis. Therapy starts with topical treatments that are applied to the skin, such as emollients. Severe forms of atopic dermatitis are often treated with systemic treatments, which are drugs that are provided as tablets or an injection. Ciclosporin A is often the first systemic therapy given. If atopic dermatitis does not get better with ciclosporin A, options available in the National Health Service are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for atopic dermatitis but have not been assessed for use in the National Health Service are abrocitinib, tralokinumab and upadacitinib. The aim of this project is to review the medical benefits, risks and value for money for the National Health Service of abrocitinib, tralokinumab and upadacitinib for the treatment of moderate-to-severe atopic dermatitis in a multiple technology appraisal. Our review found that: For children aged between 12 and 18 years, abrocitinib and a low dose of upadacitinib (15 mg) are good value for money for the National Health Service. For adults who need a first systemic treatment, upadacitinib is unlikely to be good value for money for the National Health Service. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, upadacitinib 15 mg and tralokinumab could be good value for money for the National Health Service if they are used on their own. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, but need to take it with steroid cream, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab could all be good value for money for the National Health Service.
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