Biological Therapies for Atopic Dermatitis: A Systematic Review

Abstract

Background: Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD. Objective: This work aims to summarize both label and off-label biologics on AD treatment in phase II and phase III stages, and compile evidence on the efficacy of the most-studied biologics. Methods: We conducted a comprehensive literature search through PubMed, EMBASE, and ClinicalTrials.gov to identify all documented biological therapies for AD. The criteria were further refined to focus on those treatments with the highest evidence level for AD with at least one randomized clinical trial supporting their use. Only studies or articles published in English were enrolled in this study. Findings: Primary searches identified 525 relevant articles and 27 trials. Duplicated articles and papers without a full text were excluded. Only completed trials were enrolled. We included 28 randomized controlled trials, 4 unpublished trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this work. Dupliumab, as the most widely used and investigated biologic, was reported in 1 meta-analysis and 4 trials exploring its long-term use and application in both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 inhibitors recruited were all randomized, clinical trials at phase 2–3 stage. Six different kinds of JAK inhibitors were summarized with strong evidence revealing their significant therapeutic effects on AD. There were 3 trials for nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical trial stage. Results showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety. Conclusion: The biological therapies with the most robust evidence on efficacy and long-term safety for AD treatment include dupilumab, barcitinib, abrocitinib, and delgocitinib. Most of the biologics mentioned in this review were still at the exploratory stage. This review will help practitioners advise patients seeking suitable biological therapies and offer experimental study directions for treatment.

Janus Kinase Inhibitors in the Treatment of Vitiligo: A Review

“…Tofacitinib is a selective JAK1 and JAK3 inhibitor approved to treat moderate and severe rheumatoid arthritis (43). Both oral and topical forms of tofacitinib have shown efficacy in treating immune-mediated skin disorders, including plaque psoriasis, atopic dermatitis, and alopecia areata (58)(59)(60). Oral administration of tofacitinib was first used in a female patient with vitiligo who had approximately 10% depigmentation in her total body surface area, which was unresponsive to the traditional application of topical corticosteroid ointment and tacrolimus ointment.…”

From Emollients to Biologicals: Targeting Atopic Dermatitis

“…Many further monoclonal antibodies are under study in AD, mainly targeting type 2 inflammation [ 96 , 97 , 98 ]. Tralokinumab and lebrikizumab are anti-IL-13 monoclonal antibodies that bind soluble IL-13 thus preventing IL-13Rα heterodimerization with IL-4Rα and consequent signaling via the IL-4R [ 96 , 97 , 98 ].…”

“…Many further monoclonal antibodies are under study in AD, mainly targeting type 2 inflammation [ 96 , 97 , 98 ]. Tralokinumab and lebrikizumab are anti-IL-13 monoclonal antibodies that bind soluble IL-13 thus preventing IL-13Rα heterodimerization with IL-4Rα and consequent signaling via the IL-4R [ 96 , 97 , 98 ]. They both induced clinical improvement compared to placebo in AD patients: tralokinumab was superior to placebo at 16 weeks of treatment and it was well tolerated up to 52 weeks of treatment [ 99 , 100 ].…”

The Role of Galectin-9 as Mediator of Atopic Dermatitis: Effect on Keratinocytes

“…A similar pattern of LGALS9 expression was detected in the prim keratinocytes under IL-17A stimulation, however, under other inflammatory stimuli expression pattern of LGALS9 changes completely (Figure 4g). Interestingly, mRNA transcriptomics from the GSE130588 study showed that t ment with dupilumab, an efficient biologic therapy for AD that inhibits signaling of IL-4 and IL-13 [14,15], downregulated the transcriptional levels of the LGALS9 gen lesion skins from AD patients compared to control skins (Figure 4h). Nonlesion AD s Expression of Gal-9 in human skin biopsies were analyzed in both control and AD patient samples.…”

“…No alterations were detected in the IL-8 and RANTES release by the IL-4-or IL-17-stimulated keratinocytes (Figure 5e,f,h,i). Interestingly, mRNA transcriptomics from the GSE130588 study showed that treatment with dupilumab, an efficient biologic therapy for AD that inhibits signaling of both IL-4 and IL-13 [14,15], downregulated the transcriptional levels of the LGALS9 gene in lesion skins from AD patients compared to control skins (Figure 4h). Nonlesion AD skins also showed decreased levels of LGALS9 in weeks 0 and 16 of drug treatment compared to control skins (Figure 4h).…”