Doreen Siegels1, Annice Heratizadeh2, Susanne Abraham1,3, Jonas Binnmyr4,5, Knut Brockow6, Alan D Irvine7,8, Susanne Halken9, Charlotte G Mortz10, Carsten Flohr11, Peter Schmid-Grendelmeier12,13, Lauri-Ann Van der Poel14, Antonella Muraro15, Stephan Weidinger16, Thomas Werfel2, Jochen Schmitt1. 1. Center for Evidence-Based Healthcare, University Hospital Dresden, Dresden, Germany. 2. Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy Hannover Medical School, Hannover, Germany. 3. Department of Dermatology, Medical Faculty Carl Gustav Carus, University Allergy Center, TU Dresden, Dresden, Germany. 4. The Swedish Asthma- and Allergy Association, Stockholm, Sweden. 5. The Swedish Asthma- and Allergy Research Foundation, Stockholm, Sweden. 6. Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, Germany. 7. Department of Clinical Medicine, Trinity College Dublin, Ireland. 8. Dermatology, Children's Health Ireland, National Children's Research Centre, Dublin, Ireland. 9. Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark. 10. Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis (ORCA), Odense University Hospital, Odense, Denmark. 11. Unit for Population-Based Dermatology Research, St John's Institute of Dermatology, Guy's & St Thomas' NHS Foundation Trust and King's College London, London, UK. 12. Allergy Unit, Department of Dermatology, University Hospital of Zurich, Zurich. 13. Christine-Kuehne Center for Allergy Research and Education CK_CARE, Davos, Switzerland. 14. Department of Paediatric Allergy, Guy's and St Thomas' NHS Foundation Trust, UK. 15. Department of Woman and Child Health, Food Allergy Referral Centre, Padua University Hospital, Padua, Italy. 16. Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Abstract
BACKGROUND: As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)," we critically appraised evidence on systemic treatments for moderate-to-severe AD. METHODS: We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate. RESULTS: 50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon-gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta-analyses were indicated for the efficacy of baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (ie 16-week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short-term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI. CONCLUSION: The most robust, replicated high-quality trial evidence is present for the efficacy and safety of dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.
BACKGROUND: As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)," we critically appraised evidence on systemic treatments for moderate-to-severe AD. METHODS: We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate. RESULTS: 50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon-gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta-analyses were indicated for the efficacy of baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (ie 16-week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short-term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI. CONCLUSION: The most robust, replicated high-quality trial evidence is present for the efficacy and safety of dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.
Authors: Jonathan I Silverberg; H Chih-Ho Hong; Jacob P Thyssen; Brian M Calimlim; Avani Joshi; Henrique D Teixeira; Eric B Collins; Marjorie M Crowell; Scott J Johnson; April W Armstrong Journal: Dermatol Ther (Heidelb) Date: 2022-04-18