Systemic treatments in the management of atopic dermatitis: A systematic review and meta‐analysis

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.

Comparative efficacy and safety of systemic therapies used in moderate‐to‐severe atopic dermatitis: a systematic literature review and network meta‐analysis

“… 24 Another recent NMA of systemic therapies reported robust evidence for baricitinib, dupilumab and ciclosporin‐A. 25 The objective of this study was to provide an up‐to‐date analysis of the comparative efficacy and safety of systemic treatments for moderate‐to‐severe AD as monotherapy and in combination with topical therapies.…”

Low numbers of cytokine transcripts drive inflammatory skin diseases by initiating amplification cascades in localized epidermal clusters

“…The distribution matched that of antigens previously described in ncISD. In psoriasis, cytokine-secreting leukocytes were almost exclusively found throughout the epidermis, where epidermal and melanocytic autoantigens of psoriasis are expressed, e.g., ADAMTSL5(17), LL37 (18), or lipid antigens presented via CD1 (12). By contrast, antigens reported in lichen are located at the interface of the basal epidermis and the upper dermis, e.g., DSG (19), and several Hom s proteins (20) as potential antigens of AD are expressed in a similar location.…”

“…Likewise, AD is successfully treated with antibodies targeting cytokines of type 2 immune cells, such as IL-13 (11,12). However, without models to predict therapeutic responses, many patients do not respond to a given therapy.…”

Contemporary Grand Challenges and Opportunities in Skin Allergies

“…Multiple immune pathways have been associated with atopic dermatitis and different classes of topical and systemic treatments have been developed (10). Among them are anti-cytokine biologicals, receptor antagonists, and tyrosine kinase inhibitors ( Table 1).…”