Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

被引：388

作者：

Bieber, Thomas ^{[1
,2
,3
]}

机构：

[1] Univ Hosp, Dept Dermatol & Allergy, Bonn, Germany

[2] Christine Kuhne Ctr Allergy Res & Educ, Davos, Switzerland

[3] Davos Biosci, Davos, Switzerland

来源：

NATURE REVIEWS DRUG DISCOVERY | 2022年 / 21卷 / 01期

关键词：

HISTAMINE H-4 RECEPTOR; EPIDERMAL LANGERHANS CELLS; JANUS KINASE INHIBITOR; HIGH-AFFINITY RECEPTOR; SKIN BARRIER FUNCTION; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; PHOSPHODIESTERASE-4; INHIBITOR; EUROPEAN GUIDELINES; AMERICAN ACADEMY;

D O I：

10.1038/s41573-021-00266-6

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a complex pathophysiology that underlies a wide spectrum of clinical phenotypes. AD remains challenging to treat owing to the limited response to available therapies. However, recent advances in understanding of disease mechanisms have led to the discovery of novel potential therapeutic targets and drug candidates. In addition to regulatory approval for the IL-4Ra inhibitor dupilumab, the anti-IL-13 inhibitor tralokinumab and the JAK1/2 inhibitor baricitinib in Europe, there are now more than 70 new compounds in development. This Review assesses the various strategies and novel agents currently being investigated for AD and highlights the potential for a precision medicine approach to enable prevention and more effective long-term control of this complex disease. Recent advances in understanding of the complex phenotype and mechanisms underlying atopic dermatitis (AD) have revealed multiple new potential targets for pharmacological intervention. Here, Bieber reviews therapeutic strategies and assesses the expanding pipeline for the therapy of AD, highlighting the potential for a precision medicine approach to the management of this complex disorder.

引用

页码：21 / 40

页数：20

共 263 条

[1]

Abboud D, 2017, DRUG DISCOV TODAY, V22, P702, DOI 10.1016/j.drudis.2016.11.023

[2] Implementation of dupilumab in routine care of atopic eczema: results from the German national registry TREATgermany [J].

Abraham, S. ;

Haufe, E. ;

Harder, I. ;

Heratizadeh, A. ;

Kleinheinz, A. ;

Wollenberg, A. ;

Weisshaar, E. ;

Augustin, M. ;

Wiemers, F. ;

Zink, A. ;

Biedermann, T. ;

Kiedrowski, R. ;

Hilgers, M. ;

Worm, M. ;

Pawlak, M. ;

Sticherling, M. ;

Fell, I. ;

Handrick, C. ;

Schaekel, K. ;

Staubach, P. ;

Asmussen, A. ;

Schwarz, B. ;

Bell, M. ;

Neubert, K. ;

Effendy, I. ;

Bieber, T. ;

Homey, B. ;

Gerlach, B. ;

Tchitcherina, E. ;

Stahl, M. ;

Schwichtenberg, U. ;

Rossbacher, J. ;

Buck, P. ;

Mempel, M. ;

Beissert, S. ;

Werfel, T. ;

Weidinger, S. ;

Schmitt, J. .

BRITISH JOURNAL OF DERMATOLOGY, 2020, 183 (02) :382-384

[3] Revisiting Therapies for Atopic Dermatitis that Failed Clinical Trials [J].

Agnihotri, Gaurav ;

Lio, Peter A. .

CLINICAL DRUG INVESTIGATION, 2020, 40 (05) :421-431

[4] Type 2 immunity in the skin and lungs [J].

Akdis, Cezmi A. ;

Arkwright, Peter D. ;

Bruggen, Marie-Charlotte ;

Busse, William ;

Gadina, Massimo ;

Guttman-Yassky, Emma ;

Kabashima, Kenji ;

Mitamura, Yasutaka ;

Vian, Laura ;

Wu, Jianni ;

Palomares, Oscar .

ALLERGY, 2020, 75 (07) :1582-1605

[5] Conjunctivitis in dupilumab clinical trials [J].

Akinlade, B. ;

Guttman-Yassky, E. ;

de Bruin-Weller, M. ;

Simpson, E. L. ;

Blauvelt, A. ;

Cork, M. J. ;

Prens, E. ;

Asbell, P. ;

Akpek, E. ;

Corren, J. ;

Bachert, C. ;

Hirano, I. ;

Weyne, J. ;

Korotzer, A. ;

Chen, Z. ;

Hultsch, T. ;

Zhu, X. ;

Davis, J. D. ;

Mannent, L. ;

Hamilton, J. D. ;

Teper, A. ;

Staudinger, H. ;

Rizova, E. ;

Pirozzi, G. ;

Graham, N. M. H. ;

Shumel, B. ;

Ardeleanu, M. ;

Wollenberg, A. .

BRITISH JOURNAL OF DERMATOLOGY, 2019, 181 (03) :459-473

[6] Exploring Sphingolipid Implications in Neurodegeneration [J].

Alessenko, Alice V. ;

Albi, Elisabetta .

FRONTIERS IN NEUROLOGY, 2020, 11

[7] The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling [J].

Amano, Wataru ;

Nakajima, Saeko ;

Kunugi, Hayato ;

Numata, Yasuharu ;

Kitoh, Akihiko ;

Egawa, Gyohei ;

Dainichi, Teruki ;

Honda, Tetsuya ;

Otsuka, Atsushi ;

Kimoto, Yukari ;

Yamamoto, Yasuo ;

Tanimoto, Atsuo ;

Matsushita, Mutsuyoshi ;

Miyachi, Yoshiki ;

Kabashima, Kenji .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2015, 136 (03) :667-+

[8] Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma [J].

Andersen Y.M.F. ;

Egeberg A. ;

Skov L. ;

Thyssen J.P. .

Current Dermatology Reports, 2017, 6 (1) :35-41

[9] A Phase 1b, Randomized, Single-Center Trial of Topical Cerdulatinib (DMVT-502) in Patients with Mild-to-Moderate Atopic Dermatitis [J].

不详 .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2021, 141 (07) :1847-+

[10] Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release [J].

Archer, Nathan K. ;

Jo, Jay-Hyun ;

Lee, Steven K. ;

Kim, Dongwon ;

Smith, Barbara ;

Ortines, Roger V. ;

Wang, Yu ;

Marchitto, Mark C. ;

Ravipati, Advaitaa ;

Cai, Shuting S. ;

Dillen, Carly A. ;

Liu, Haiyun ;

Miller, Robert J. ;

Ashbaugh, Alyssa G. ;

Uppal, Angad S. ;

Oyoshi, Michiko K. ;

Malhotra, Nidhi ;

Hoff, Sabine ;

Garza, Luis A. ;

Kong, Heidi H. ;

Segre, Julia A. ;

Geha, Raif S. ;

Miller, Lloyd S. .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2019, 143 (04) :1426-+

← 1 2 3 4 5 6 7 8 9 10 →