# Novel Therapeutic Strategies for Atopic Dermatitis: Biomarker Modulation and Clinical Implications. A Systematic Review

**Authors:** Noelia Moreiras-Arias, Juan José Nieto-Fontarigo, Francisco Javier Salgado, Daniel González-Vilas, Carmen Paredes-Suárez, Enma Combo-García, Carmen Rodríguez-Otero, Ángeles Flórez

PMC · DOI: 10.1007/s12016-025-09129-z · 2026-01-29

## TL;DR

This systematic review explores new treatments for atopic dermatitis and their effects on biomarkers and clinical outcomes.

## Contribution

The paper identifies key biomarkers and treatment responses in atopic dermatitis through a systematic review of recent studies.

## Key findings

- Biologic agents like dupilumab consistently reduce biomarkers such as CCL17/TARC, LDH, and total IgE.
- Transcriptomic and proteomic analyses show normalization of Th2/Th22 inflammation and improved skin barrier genes.
- Microbiome studies indicate reduced Staphylococcus aureus colonization following treatment.

## Abstract

Advances in the understanding of atopic dermatitis (AD) pathogenesis have driven the development of innovative systemic therapies targeting key immunologic pathways. This systematic review summarizes current evidence on the impact of biologic agents, Janus kinase (JAK) inhibitors, and other emerging treatments on AD-related biomarkers and their correlation with clinical outcomes. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science for studies published between 2014 and 2024. Eighty studies met the inclusion criteria. Dupilumab was the most extensively investigated therapy, followed by tralokinumab, JAK inhibitors, and novel agents such as amlitelimab, stapokibart, and tezepelumab. Across drug classes, consistent reductions in CCL17/TARC, LDH, and total IgE levels were observed, generally paralleling clinical improvement in EASI and SCORAD scores. Transcriptomic and proteomic analyses revealed normalization of Th2/Th22 inflammatory signatures and restoration of barrier-related gene expression, while microbiome studies showed a reduction in Staphylococcus aureus colonization. Despite these advances, the heterogeneity of study designs and analytical techniques limits the comparability of results. CCL17 and LDH currently represent the most reliable biomarkers associated with disease severity and treatment response, although their limited specificity restricts clinical applicability. Future research should aim to validate integrated biomarker panels combining immunologic, transcriptomic, and microbiomic data to enable precision medicine approaches in atopic dermatitis management.

The online version contains supplementary material available at 10.1007/s12016-025-09129-z.

## Linked entities

- **Proteins:** CCL17 (C-C motif chemokine ligand 17), Ldh (Lactate dehydrogenase), IGHE (immunoglobulin heavy constant epsilon)
- **Diseases:** atopic dermatitis (MONDO:0004980)

## Full-text entities

- **Genes:** CD200 (CD200 molecule) [NCBI Gene 4345] {aka MOX1, MOX2, MRC, OX-2}, IL25 (interleukin 25) [NCBI Gene 64806] {aka IL17E}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, PI3 (peptidase inhibitor 3) [NCBI Gene 5266] {aka ESI, SKALP, WAP3, WFDC14, cementoin}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, CCL26 (C-C motif chemokine ligand 26) [NCBI Gene 10344] {aka IMAC, MIP-4a, MIP-4alpha, SCYA26, TSC-1}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364] {aka CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A}, CLDN8 (claudin 8) [NCBI Gene 9073] {aka HEL-S-79}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279] {aka 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, RNASE3 (ribonuclease A family member 3) [NCBI Gene 6037] {aka ECP, RAF1, RNS3}, CERS1 (ceramide synthase 1) [NCBI Gene 10715] {aka EPM8, LAG1, LASS1, UOG1}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, PPL (periplakin) [NCBI Gene 5493], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IL4R (interleukin 4 receptor) [NCBI Gene 3566] {aka CD124, IL-4RA, IL4RA}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, SYNM (synemin) [NCBI Gene 23336] {aka DMN, SYN}, KRT16 (keratin 16) [NCBI Gene 3868] {aka CK16, FNEPPK, K16, K1CP, KRT16A, NEPPK}, TNFSF4 (TNF superfamily member 4) [NCBI Gene 7292] {aka CD134L, CD252, GP34, OX-40L, OX4OL, TNLG2B}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, FLG (filaggrin) [NCBI Gene 2312] {aka ATOD2, FLG-1, FLG1}, CCL17 (C-C motif chemokine ligand 17) [NCBI Gene 6361] {aka A-152E5.3, ABCD-2, SCYA17, TARC}, POR (cytochrome p450 oxidoreductase) [NCBI Gene 5447] {aka CPR, CYPOR, P450R}, IL9 (interleukin 9) [NCBI Gene 3578] {aka HP40, IL-9, P40}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, CCL22 (C-C motif chemokine ligand 22) [NCBI Gene 6367] {aka A-152E5.1, ABCD-1, DC/B-CK, MDC, SCYA22, STCP-1}, TSLP (thymic stromal lymphopoietin) [NCBI Gene 85480], IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, CCL18 (C-C motif chemokine ligand 18) [NCBI Gene 6362] {aka AMAC-1, AMAC1, CKb7, DC-CK1, DCCK1, MIP-4}, FCER2 (Fc epsilon receptor II) [NCBI Gene 2208] {aka BLAST-2, CD23, CD23A, CLEC4J, FCE2, FCErII}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, CLDN1 (claudin 1) [NCBI Gene 9076] {aka CLD1, ILVASC, SEMP1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, IL36B (interleukin 36 beta) [NCBI Gene 27177] {aka FIL1, FIL1-(ETA), FIL1H, FILI-(ETA), IL-1F8, IL-1H2}, TNFRSF4 (TNF receptor superfamily member 4) [NCBI Gene 7293] {aka ACT35, CD134, IMD16, OX40, TXGP1L}, KRT10 (keratin 10) [NCBI Gene 3858] {aka BCIE, BIE, CK10, EHK, EHK2, EHK2A}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, CP (ceruloplasmin) [NCBI Gene 1356] {aka AB073614, CP-2}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, S100A7 (S100 calcium binding protein A7) [NCBI Gene 6278] {aka PSOR1, S100A7c}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, POSTN (periostin) [NCBI Gene 10631] {aka OSF-2, OSF2, PDLPOSTN, PN}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, IL31 (interleukin 31) [NCBI Gene 386653] {aka IL-31}, FA2H (fatty acid 2-hydroxylase) [NCBI Gene 79152] {aka FAAH, FAH1, FAXDC1, SCS7, SPG35}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, ELOVL3 (ELOVL fatty acid elongase 3) [NCBI Gene 83401] {aka CIG-30, CIG30}
- **Diseases:** Fibrosis (MESH:D005355), eosinophilia (MESH:D004802), asthma (MESH:D001249), atopic (MESH:C566404), dermatitis (MESH:D003872), immune dysregulation (OMIM:614878), systemic (MESH:D015619), conjunctivitis (MESH:D003231), epidermal hyperplasia (MESH:D006965), allergic rhinoconjunctivitis (OMIM:613207), skin disease (MESH:D012871), allergic (MESH:D004342), Dermatophagoides farinae (MESH:D000092542), nasal polyposis (MESH:D009668), eosinophilic esophagitis (MESH:D057765), Itching (MESH:D011537), Inflammation (MESH:D007249), psoriasis (MESH:D011565), AD (MESH:D003876), atherosclerosis (MESH:D050197), Eczema (MESH:D004485), eczematous lesions (MESH:D017443), flexural disease (MESH:C566278), food allergy (MESH:D005512)
- **Chemicals:** TEWL (-), 18F (MESH:C000615276), tezepelumab (MESH:C000622721), lipid (MESH:D008055), lebrikizumab (MESH:C561806), Tralokinumab (MESH:C574065), 18F-FDG (MESH:D019788), baricitinib (MESH:C000596027), upadacitinib (MESH:C000613732), nemolizumab (MESH:C000612881), ASN002 (MESH:C000707471), Dupilumab (MESH:C582203), water (MESH:D014867), Abrocitinib (MESH:C000634427), ribose (MESH:D012266)
- **Species:** Olea europaea (common olive, species) [taxon 4146], Staphylococcus aureus (species) [taxon 1280], Canis lupus familiaris (dog, subspecies) [taxon 9615], aureus [taxon 46170], Homo sapiens (human, species) [taxon 9606], Parietaria judaica (species) [taxon 33127]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12855363/full.md

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Source: https://tomesphere.com/paper/PMC12855363