TY - JOUR
T1 - Systemic treatments in the management of atopic dermatitis
T2 - A systematic review and meta-analysis
AU - the European Academy of Allergy, Clinical Immunology Atopic Dermatitis Guideline group
AU - Siegels, Doreen
AU - Heratizadeh, Annice
AU - Abraham, Susanne
AU - Binnmyr, Jonas
AU - Brockow, Knut
AU - Irvine, Alan D.
AU - Halken, Susanne
AU - Mortz, Charlotte G.
AU - Flohr, Carsten
AU - Schmid-Grendelmeier, Peter
AU - Van der Poel, Lauri Ann
AU - Muraro, Antonella
AU - Weidinger, Stephan
AU - Werfel, Thomas
AU - Schmitt, Jochen
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - atopic dermatitis
KW - biologics
KW - dermatology
UR - http://www.scopus.com/inward/record.url?scp=85097023645&partnerID=8YFLogxK
U2 - 10.1111/all.14631
DO - 10.1111/all.14631
M3 - Review article
C2 - 33074565
AN - SCOPUS:85097023645
SN - 0105-4538
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
ER -