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Primary efficacy outcomes were clinical signs, AD symptoms and health\u2010related 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\u2010analyses were conducted where appropriate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon\u2010gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta\u2010analyses 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\u2010term (ie 16\u2010week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short\u2010term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The most robust, replicated high\u2010quality trial evidence is present for the efficacy and safety of dupilumab for up to 1\u00a0year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence\u2010based conclusions for all other systemic treatments. 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