Current and emerging biologic and small molecule therapies for atopic dermatitis

References

• Gittler JK, Shemer A, Suarez-Farinas M, et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012 Dec;130(6):1344–1354.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis–part I: clinical and pathologic concepts. J Allergy Clin Immunol. 2011 May;127(5):1110–1118.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013 Nov;132(5):1132–1138.
   PubMed Web of Science ®Google Scholar
• Williams H, Flohr C. How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. J Allergy Clin Immunol. 2006 Jul;118(1):209–213.
   PubMed Web of Science ®Google Scholar
• Kim MJ, Kang TW, Cho EA, et al. Prevalence of atopic dermatitis among Korean adults visiting health service center of the Catholic Medical Center in Seoul metropolitan area, Korea. J Korean Med Sci. 2010 Dec;25(12):1828–1830.
   PubMed Web of Science ®Google Scholar
• Hanifin JM, Reed ML, Eczema P, et al. A population-based survey of eczema prevalence in the United States. Dermatitis. 2007 Jun;18(2):82–91.
   PubMed Web of Science ®Google Scholar
• Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014 Jul;71(1):116–132.
   PubMed Web of Science ®Google Scholar
• Schneider L, Tilles S, Lio P, et al. Atopic dermatitis: a practice parameter update 2012. J Allergy Clin Immunol. 2013 Feb;131(2):295-9e1-27.
   PubMed Web of Science ®Google Scholar
• Roekevisch E, Spuls PI, Kuester D, et al. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014 Feb;133(2):429–438.
   PubMed Web of Science ®Google Scholar
• Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014 Aug;71(2):327–349.
   PubMed Web of Science ®Google Scholar
• Boguniewicz M, Fonacier L, Guttman-Yassky E, et al. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018 Jan;120(1):10–22 e2.
   PubMed Web of Science ®Google Scholar
• Drucker AM, Eyerich K, de Bruin-Weller MS, et al. Use of systemic corticosteroids for atopic dermatitis: international eczema council consensus statement. Br J Dermatol. 2018 Mar;178(3):768–775.
   PubMed Web of Science ®Google Scholar
• Lynde CW, Bourcier M, Gooderham M, et al. A treatment algorithm for moderate to severe atopic dermatitis in adults. J Cutan Med Surg. 2018 Jan/Feb;22(1):78–83.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Bissonnette R, Ungar B, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in atopic dermatitis patients. J Allergy Clin Immunol. 2018 Sep. 5.
   Web of Science ®Google Scholar
• Simpson EL, Gadkari A, Worm M, et al. Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): a phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD). J Am Acad Dermatol. 2016 Sep;75(3):506–515.
   PubMed Web of Science ®Google Scholar
• Hamilton JD, Suarez-Farinas M, Dhingra N, et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2014 Dec;134(6):1293–1300.
   PubMed Web of Science ®Google Scholar
• Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017 Jun 10;389(10086):2287–2303.
   PubMed Web of Science ®Google Scholar
• Beck LA, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014 Jul 10;371(2):130–139.
   PubMed Web of Science ®Google Scholar
• Bieber T. Atopic dermatitis. N Engl J Med. 2008 Apr 3;358(14):1483–1494.
   PubMed Web of Science ®Google Scholar
• Czarnowicki T, Krueger JG, Guttman-Yassky E. Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. J Allergy Clin Immunol Pract. 2014 Jul-Aug;2(4):371–379. quiz 380-1.
   PubMed Web of Science ®Google Scholar
• Elias PM, Hatano Y, Williams ML. Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. J Allergy Clin Immunol. 2008 Jun;121(6):1337–1343.
   PubMed Web of Science ®Google Scholar
• Elias PM, Schmuth M. Abnormal skin barrier in the etiopathogenesis of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2009 Oct;9(5):437–446.
   PubMed Web of Science ®Google Scholar
• Oliva M, Renert-Yuval Y, Guttman-Yassky E. The‘omics’ revolution: redefining the understanding and treatment of allergic skin diseases. Curr Opin Allergy Clin Immunol. 2016 Oct;16(5):469–476.
   PubMed Web of Science ®Google Scholar
• Brunner PM, Suarez-Farinas M, He H, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017 Aug 18;7(1):8707.
   PubMed Web of Science ®Google Scholar
• Esaki H, Ewald DA, Ungar B, et al. Identification of novel immune and barrier genes in atopic dermatitis by means of laser capture microdissection. J Allergy Clin Immunol. 2015 Jan;135(1):153–163.
   PubMed Web of Science ®Google Scholar
• Suarez-Farinas M, Ungar B, Correa da Rosa J, et al. RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications. J Allergy Clin Immunol. 2015 May;135(5):1218–1227.
   PubMed Web of Science ®Google Scholar
• Ungar B, Garcet S, Gonzalez J, et al. An integrated model of atopic dermatitis biomarkers highlights the systemic nature of the disease. J Invest Dermatol. 2017 Mar;137(3):603–613.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Krueger JG. Atopic dermatitis and psoriasis: two different immune diseases or one spectrum? Curr Opin Immunol. 2017 Oct;48:68–73.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Krueger JG, Lebwohl MG. Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment. Exp Dermatol. 2018 Apr;27(4):409–417.
   PubMed Web of Science ®Google Scholar
• Harden JL, Krueger JG, Bowcock AM. The immunogenetics of psoriasis: a comprehensive review. J Autoimmun. 2015 Nov;64:66–73.
   PubMed Web of Science ®Google Scholar
• Hawkes JE, Yan BY, Chan TC, et al. Discovery of the IL-23/IL-17 signaling pathway and the treatment of psoriasis. J Immunol. 2018 Sep 15;201(6):1605–1613.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis–part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011 Jun;127(6):1420–1432.
   PubMed Web of Science ®Google Scholar
• Esaki H, Brunner PM, Renert-Yuval Y, et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol. 2016 Dec;138(6):1639–1651.
   PubMed Web of Science ®Google Scholar
• Noda S, Suarez-Farinas M, Ungar B, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015 Nov;136(5):1254–1264.
   PubMed Web of Science ®Google Scholar
• Suarez-Farinas M, Dhingra N, Gittler J, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013 Aug;132(2):361–370.
   PubMed Web of Science ®Google Scholar
• Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups-variations in epidemiology, genetics, clinical presentation and treatment. Exp Dermatol. 2018 Apr;27(4):340–357.
   PubMed Web of Science ®Google Scholar
• Sanyal RD, Pavel AB, Glickman J, et al. Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation. Ann Allergy Asthma Immunol. 2018 Sep 6;122(1):99–110.
   PubMed Web of Science ®Google Scholar
• Wen HC, Czarnowicki T, Noda S, et al. Serum from Asian patients with atopic dermatitis is characterized by TH2/TH22 activation, which is highly correlated with nonlesional skin measures. J Allergy Clin Immunol. 2018 Jul;142(1):324–328 e11.
   PubMed Web of Science ®Google Scholar
• Chan TC, Sanyal RD, Pavel AB, et al. Atopic dermatitis in Chinese patients shows TH2/TH17 skewing with psoriasiform features. J Allergy Clin Immunol. 2018 Sep;142(3):1013–1017.
   PubMed Web of Science ®Google Scholar
• Leung DY, Boguniewicz M, Howell MD, et al. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651–657.
   PubMed Web of Science ®Google Scholar
• Kim BE, Leung DY, Boguniewicz M, et al. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008 Mar;126(3):332–337.
   PubMed Web of Science ®Google Scholar
• Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009 Sep;124(3 Suppl 2):R7–R12.
   PubMed Web of Science ®Google Scholar
• Kagami S, Saeki H, Komine M, et al. Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells. Clin Exp Immunol. 2005 Sep;141(3):459–466.
   PubMed Web of Science ®Google Scholar
• Travers JB. Toxic interaction between Th2 cytokines and staphylococcus aureus in atopic dermatitis. J Invest Dermatol. 2014 Aug;134(8):2069–2071.
   PubMed Web of Science ®Google Scholar
• Nomura I, Goleva E, Howell MD, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003 Sep 15;171(6):3262–3269.
   PubMed Web of Science ®Google Scholar
• Zheng T, Oh MH, Oh SY, et al. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 2009 Mar;129(3):742–751.
   PubMed Web of Science ®Google Scholar
• Zhu Z, Oh MH, Yu J, et al. The role of TSLP in IL-13-induced atopic march. Sci Rep. 2011;1:23.
   PubMed Web of Science ®Google Scholar
• Tazawa T, Sugiura H, Sugiura Y, et al. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res. 2004 Apr;295(11):459–464.
   PubMed Web of Science ®Google Scholar
• Frampton JE, Blair HA. Dupilumab: a review in moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2018 Aug;19(4):617–624.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016 Dec 15;375(24):2335–2348.
   PubMed Web of Science ®Google Scholar
• Thaci D, Simpson EL, Beck LA, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016 Jan 2;387(10013):40–52.
   PubMed Web of Science ®Google Scholar
• Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine. 2015 Sep;75(1):68–78.
   PubMed Web of Science ®Google Scholar
• Treister AD, Kraff-Cooper C, Lio PA Risk factors for dupilumab-associated conjunctivitis in patients with atopic dermatitis. JAMA Dermatol. 2018 Aug 29;154(10):1208–1211.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Paller AS, Siegfried EC, et al. Dupilumab Efficacy and Safety in Adolescents with Moderate-to-Severe Atopic Dermatitis: Results from a Multicenter, Randomized, PlaceboControlled, Double-Blind, Parallel-Group, Phase 3 Study [abstract]. 27th European academy of dermatology and venereology (EADV) congress, Paris: France; 2018 September 15.
   Google Scholar
• Ultsch M, Bevers J, Nakamura G, et al. Structural basis of signaling blockade by anti-IL-13 antibody lebrikizumab. J Mol Biol. 2013 Apr 26;425(8):1330–1339.
   PubMed Web of Science ®Google Scholar
• Popovic B, Breed J, Rees DG, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Ralpha1 and IL-13Ralpha2. J Mol Biol. 2017 Jan 20;429(2):208–219.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Flohr C, Eichenfield LF, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018 May;78(5):863–871 e11.
   PubMed Web of Science ®Google Scholar
• Hanania NA, Korenblat P, Chapman KR, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016 Oct;4(10):781–796.
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Howell MD, Guttman-Yassky E, et al. Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2018 Jun 12;143(1):135–141.
   Web of Science ®Google Scholar
• Izuhara K, Arima K, Ohta S, et al. Periostin in allergic inflammation. Allergol Int. 2014;63(2):143–151.
   Web of Science ®Google Scholar
• Pham T-H, Damera G, Brohawn PZ, et al. Dipeptidyl Peptidase-4 (DPP-4) is a novel predictive biomarker for the investigational Anti-IL-13 targeted therapy tralokinumab. B101. Phenotyping Of Asthma In The Era Of Biomarkers And Omics. 2016 May; A4332–A4332
   Google Scholar
• Stephan M, Suhling H, Schade J, et al. Effects of dipeptidyl peptidase-4 inhibition in an animal model of experimental asthma: a matter of dose, route, and time. Physiol Rep. 2013 Oct;1(5):e00095.
   PubMedGoogle Scholar
• Blanchard C, Mingler MK, McBride M, et al. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses. Mucosal Immunol. 2008 Jul;1(4):289–296.
   PubMed Web of Science ®Google Scholar
• Piper E, Brightling C, Niven R, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013 Feb;41(2):330–338.
   PubMed Web of Science ®Google Scholar
• Bilsborough J, Leung DY, Maurer M, et al. IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J Allergy Clin Immunol. 2006 Feb;117(2):418–425.
   PubMed Web of Science ®Google Scholar
• Dillon SR, Sprecher C, Hammond A, et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat Immunol. 2004 Jul;5(7):752–760.
   PubMed Web of Science ®Google Scholar
• Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2014 Feb;133(2):448–460.
   PubMed Web of Science ®Google Scholar
• Nobbe S, Dziunycz P, Muhleisen B, et al. IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis. Acta Derm Venereol. 2012 Jan;92(1):24–28.
   PubMed Web of Science ®Google Scholar
• Brunner PM, Leung DYM, Guttman-Yassky E. Immunologic, microbial, and epithelial interactions in atopic dermatitis. Ann Allergy Asthma Immunol. 2018 Jan;120(1):34–41.
   PubMed Web of Science ®Google Scholar
• Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017 Apr;139(4S):S65–S76.
   PubMed Web of Science ®Google Scholar
• Grimstad O, Sawanobori Y, Vestergaard C, et al. Anti-interleukin-31-antibodies ameliorate scratching behaviour in NC/Nga mice: a model of atopic dermatitis. Exp Dermatol. 2009 Jan;18(1):35–43.
   PubMed Web of Science ®Google Scholar
• Cornelissen C, Luscher-Firzlaff J, Baron JM, et al. Signaling by IL-31 and functional consequences. Eur J Cell Biol. 2012 Jun-Jul;91(6–7):552–566.
   PubMed Web of Science ®Google Scholar
• Cornelissen C, Marquardt Y, Czaja K, et al. IL-31 regulates differentiation and filaggrin expression in human organotypic skin models. J Allergy Clin Immunol. 2012 Feb;129(2):426–433. 433 e1-8.
   PubMed Web of Science ®Google Scholar
• Cheung PF, Wong CK, Ho AW, et al. Activation of human eosinophils and epidermal keratinocytes by Th2 cytokine IL-31: implication for the immunopathogenesis of atopic dermatitis. Int Immunol. 2010 Jun;22(6):453–467.
   PubMed Web of Science ®Google Scholar
• Ruzicka T, Hanifin JM, Furue M, et al. Anti-Interleukin-31 receptor a antibody for atopic dermatitis. N Engl J Med. 2017 Mar 2;376(9):826–835.
   PubMed Web of Science ®Google Scholar
• Kabashima K, Furue M, Hanifin JM, et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: randomized, phase II, long-term extension study. J Allergy Clin Immunol. 2018 Oct;142(4):1121–1130 e7.
   PubMed Web of Science ®Google Scholar
• Boniface K, Diveu C, Morel F, et al. Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation. J Immunol. 2007 Apr 1;178(7):4615–4622.
   PubMed Web of Science ®Google Scholar
• Raap U, Gehring M, Kleiner S, et al. Human basophils are a source of - and are differentially activated by - IL-31. Clin Exp Allergy. 2017 Apr;47(4):499–508.
   PubMed Web of Science ®Google Scholar
• Richards CD, Brown TJ, Shoyab M, et al. Recombinant oncostatin M stimulates the production of acute phase proteins in HepG2 cells and rat primary hepatocytes in vitro. J Immunol. 1992 Mar 15;148(6):1731–1736.
   PubMed Web of Science ®Google Scholar
• Botelho FM, Rangel-Moreno J, Fritz D, et al. Pulmonary expression of oncostatin M (OSM) promotes inducible BALT formation independently of IL-6, despite a role for IL-6 in OSM-driven pulmonary inflammation. J Immunol. 2013 Aug 1;191(3):1453–1464.
   PubMed Web of Science ®Google Scholar
• Fritz DK, Kerr C, Botelho F, et al. Oncostatin M (OSM) primes IL-13- and IL-4-induced eotaxin responses in fibroblasts: regulation of the type-II IL-4 receptor chains IL-4Ralpha and IL-13Ralpha1. Exp Cell Res. 2009 Dec 10;315(20):3486–3499.
   PubMed Web of Science ®Google Scholar
• Fritz DK, Kerr C, Fattouh R, et al. A mouse model of airway disease: oncostatin M-induced pulmonary eosinophilia, goblet cell hyperplasia, and airway hyperresponsiveness are STAT6 dependent, and interstitial pulmonary fibrosis is STAT6 independent. J Immunol. 2011 Jan 15;186(2):1107–1118.
   PubMed Web of Science ®Google Scholar
• Gazel A, Rosdy M, Bertino B, et al. A characteristic subset of psoriasis-associated genes is induced by oncostatin-M in reconstituted epidermis. J Invest Dermatol. 2006 Dec;126(12):2647–2657.
   PubMed Web of Science ®Google Scholar
• Kwofie K, Scott M, Rodrigues R, et al. Regulation of IL-17A responses in human airway smooth muscle cells by oncostatin M. Respir Res. 2015 Feb 7;16:14.
   PubMed Web of Science ®Google Scholar
• Mozaffarian A, Brewer AW, Trueblood ES, et al. Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis. J Immunol. 2008 Nov 15;181(10):7243–7253.
   PubMed Web of Science ®Google Scholar
• Wong S, Botelho FM, Rodrigues RM, et al. Oncostatin M overexpression induces matrix deposition, STAT3 activation, and SMAD1 dysregulation in lungs of fibrosis-resistant BALB/c mice. Lab Invest. 2014 Sep;94(9):1003–1016.
   PubMed Web of Science ®Google Scholar
• Arnett HA, Escobar SS, King CT, et al. Oncostatin M receptor antigen binding proteins. Google Patents. 2017.
   Google Scholar
• Mikhak ZNJ, Bissonnette R, Siri D, et al. First-in-human study of KPL-716, anti-oncostatin M receptor beta monoclonal antibody, in healthy volunteers and subjects with atopic dermatitis. Paris, France: EADV congress; 2018.
   Google Scholar
• Liu YJ. Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med. 2006 Feb 20;203(2):269–273.
   PubMed Web of Science ®Google Scholar
• Ito T, Wang YH, Duramad O, et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med. 2005 Nov 7;202(9):1213–1223.
   PubMed Web of Science ®Google Scholar
• Fujita H, Shemer A, Suarez-Farinas M, et al. Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit parallel ability to activate T-cell subsets. J Allergy Clin Immunol. 2011 Sep;128(3):574–82 e1-12.
   Web of Science ®Google Scholar
• Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, et al. Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. J Allergy Clin Immunol. 2007 May;119(5):1210–1217.
   PubMed Web of Science ®Google Scholar
• Rogers PR, Song J, Gramaglia I, et al. OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells. Immunity. 2001 Sep;15(3):445–455.
   PubMed Web of Science ®Google Scholar
• Yoo J, Omori M, Gyarmati D, et al. Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J Exp Med. 2005 Aug 15;202(4):541–549.
   PubMed Web of Science ®Google Scholar
• Li M, Messaddeq N, Teletin M, et al. Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14795–14800.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Pavel AB, Estrada Y, et al. 453 GBR 830 induces progressive and sustained changes in atopic dermatitis biomarkers in patient skin lesions. J Invest Dermatol. 2018 May 01;138(5, Supplement):S77.
   Web of Science ®Google Scholar
• Nakagawa H, Iizuka H, Nemoto O, et al. Safety, tolerability, and efficacy of repeated intravenous infusions of a fully human anti-OX40 monoclonal antibody (KHK4083) in patients with moderate to severe atopic dermatitis. Paris, France: EADV congress; 2018.
   Google Scholar
• Miller AM. Role of IL-33 in inflammation and disease. J Inflamm (Lond). 2011 Aug 26;8(1):22.
   PubMed Web of Science ®Google Scholar
• Savinko T, Matikainen S, Saarialho-Kere U, et al. IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors. J Invest Dermatol. 2012 May;132(5):1392–1400.
   PubMed Web of Science ®Google Scholar
• Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005 Nov;23(5):479–490.
   PubMed Web of Science ®Google Scholar
• Murakami-Satsutani N, Ito T, Nakanishi T, et al. IL-33 promotes the induction and maintenance of Th2 immune responses by enhancing the function of OX40 ligand. Allergol Int. 2014;63(3):443–455.
   Web of Science ®Google Scholar
• Cherry WB, Yoon J, Bartemes KR, et al. A novel IL-1 family cytokine, IL-33, potently activates human eosinophils. J Allergy Clin Immunol. 2008 Jun;121(6):1484–1490.
   PubMed Web of Science ®Google Scholar
• Moulin D, Donze O, Talabot-Ayer D, et al. Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells. Cytokine. 2007 Dec;40(3):216–225.
   PubMed Web of Science ®Google Scholar
• Ungar B, Correa Da Rosa J, Shemer A, et al. Patch testing of food allergens promotes Th17 and Th2 responses with increased IL-33: a pilot study. Exp Dermatol. 2017 Mar;26(3):272–275.
   PubMed Web of Science ®Google Scholar
• Peng G, Mu Z, Cui L, et al. Anti-IL-33 antibody has a therapeutic effect in an atopic dermatitis murine model induced by 2, 4-dinitrochlorobenzene. Inflammation. 2018 Feb;41(1):154–163.
   PubMed Web of Science ®Google Scholar
• Londei M, Kenney B, Los G, et al. A phase 1 study of ANB020, an anti-IL-33 monoclonal antibody in healthy volunteers. J Allergy Clin. 2017;139(2):AB73.
   Web of Science ®Google Scholar
• Ogg G. Proof-of-Concept Phase-2a clinical trial of ANB020 (Anti-IL-33 antibody) in the treatment of Moderate-to-Severe adult atopic dermatitis. European Academy of Allergy and Clinical Immunology Congress; Munich, Germany; 2018.
   Google Scholar
• Nograles KE, Zaba LC, Shemer A, et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009 Jun;123(6):1244–52 e2.
   PubMed Web of Science ®Google Scholar
• Trifari S, Kaplan CD, Tran EH, et al. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol. 2009 Aug;10(8):864–871.
   PubMed Web of Science ®Google Scholar
• Noda S, Krueger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015 Feb;135(2):324–336.
   PubMed Web of Science ®Google Scholar
• Kotenko SV, Izotova LS, Mirochnitchenko OV, et al. Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. J Biol Chem. 2001 Jan 26;276(4):2725–2732.
   PubMed Web of Science ®Google Scholar
• Boniface K, Bernard FX, Garcia M, et al. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol. 2005 Mar 15;174(6):3695–3702.
   PubMed Web of Science ®Google Scholar
• Nograles KE, Zaba LC, Guttman-Yassky E, et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol. 2008 Nov;159(5):1092–1102.
   PubMed Web of Science ®Google Scholar
• Gutowska-Owsiak D, Schaupp AL, Salimi M, et al. Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. Br J Dermatol. 2011 Sep;165(3):492–498.
   PubMed Web of Science ®Google Scholar
• Fujita H. The role of IL-22 and Th22 cells in human skin diseases. J Dermatol Sci. 2013 Oct;72(1):3–8.
   PubMed Web of Science ®Google Scholar
• Niebuhr M, Scharonow H, Gathmann M, et al. Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis. J Allergy Clin Immunol. 2010 Dec;126(6):1176–83 e4.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Brunner PM, Neumann AU, et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial. J Am Acad Dermatol. 2018 May;78(5):872–881 e6.
   PubMed Web of Science ®Google Scholar
• Brunner PM, Pavel AB, Khattri S, et al. Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J Allergy Clin Immunol. 2018 Aug;143(1):142–154.
   Web of Science ®Google Scholar
• Koga C, Kabashima K, Shiraishi N, et al. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol. 2008 Nov;128(11):2625–2630.
   PubMed Web of Science ®Google Scholar
• Nakajima S, Kitoh A, Egawa G, et al. IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models. J Invest Dermatol. 2014 Aug;134(8):2122–2130.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Danilenko DM, Valdez P, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007 Feb 8;445(7128):648–651.
   PubMed Web of Science ®Google Scholar
• Rizzo HL, Kagami S, Phillips KG, et al. IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. J Immunol. 2011 Feb 1;186(3):1495–1502.
   PubMed Web of Science ®Google Scholar
• Toda M, Leung DY, Molet S, et al. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol. 2003 Apr;111(4):875–881.
   PubMed Web of Science ®Google Scholar
• Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008 May 17;371(9625):1675–1684.
   PubMed Web of Science ®Google Scholar
• Khattri S, Brunner PM, Garcet S, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017 Jan;26(1):28–35.
   PubMed Web of Science ®Google Scholar
• Vandeghinste N, Klattig J, Jagerschmidt C, et al. Neutralization of IL-17C Reduces Skin Inflammation in Mouse Models of Psoriasis and Atopic Dermatitis. J Invest Dermatol. 2018 Jul;138(7):1555–1563.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Krueger JG. IL-17C: A unique epithelial cytokine with potential for targeting across the spectrum of atopic dermatitis and psoriasis. J Invest Dermatol. 2018 Jul;138(7):1467–1469.
   PubMed Web of Science ®Google Scholar
• Thaci D. MOR106, an anti-IL-17C mAb, a potential new approach for treatment of moderate-to-severe atopic dermatitis: phase 1 study. San Diego, USA: AAD annual meeting; 2018.
   Google Scholar
• Joishy M, Alfaham M, Tuthill D. Does the severity of atopic dermatitis correlate with serum IgE levels? Pediatr Allergy Immunol. 2005 May;16(3):283.
   PubMed Web of Science ®Google Scholar
• Leung DY. Role of IgE in atopic dermatitis. Curr Opin Immunol. 1993 Dec;5(6):956–962.
   PubMed Web of Science ®Google Scholar
• Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011 Dec;41(3):298–310.
   PubMed Web of Science ®Google Scholar
• Wang HH, Li YC, Huang YC. Efficacy of omalizumab in patients with atopic dermatitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2016 Dec;138(6):1719–1722 e1.
   PubMed Web of Science ®Google Scholar
• Hotze M, Baurecht H, Rodriguez E, et al. Increased efficacy of omalizumab in atopic dermatitis patients with wild-type filaggrin status and higher serum levels of phosphatidylcholines. Allergy. 2014 Jan;69(1):132–135.
   PubMed Web of Science ®Google Scholar
• Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013 Jul 1;2(3):e24137.
   PubMedGoogle Scholar
• Villarino AV, Kanno Y, O’Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017 Mar 22;18(4):374–384.
   PubMed Web of Science ®Google Scholar
• Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009 Mar;228(1):273–287.
   PubMed Web of Science ®Google Scholar
• Wohlmann A, Sebastian K, Borowski A, et al. Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function. Biol Chem. 2010 Feb-Mar;391(2–3):181–186.
   PubMed Web of Science ®Google Scholar
• Kaplan MH, Schindler U, Smiley ST, et al. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity. 1996 Mar;4(3):313–319.
   PubMed Web of Science ®Google Scholar
• Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007 Jul;120(1):150–155.
   PubMed Web of Science ®Google Scholar
• Hirahara K, Ghoreschi K, Laurence A, et al. Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. Cytokine Growth Factor Rev. 2010 Dec;21(6):425–434.
   PubMed Web of Science ®Google Scholar
• Lee CH, Hong CH, Yu WT, et al. Mechanistic correlations between two itch biomarkers, cytokine interleukin-31 and neuropeptide beta-endorphin, via STAT3/calcium axis in atopic dermatitis. Br J Dermatol. 2012 Oct;167(4):794–803.
   PubMed Web of Science ®Google Scholar
• O’Shea JJ, Kontzias A, Yamaoka K, et al. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013 Apr;72(Suppl 2):ii111–5.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Silverberg JI, Nemoto O, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. Epub 2018 Feb 1.
   Web of Science ®Google Scholar
• Cotter DG, Schairer D, Eichenfield L. Emerging therapies for atopic dermatitis: JAK inhibitors. J Am Acad Dermatol. 2018 Mar;78(3S1):S53–S62.
   PubMedGoogle Scholar
• Jiang H, Harris MB, Rothman P. IL-4/IL-13 signaling beyond JAK/STAT. J Allergy Clin Immunol. 2000 Jun;105(6 Pt 1):1063–1070.
   PubMed Web of Science ®Google Scholar
• Gooderham M, Forman S, Bissonnette R PF-04965842, a selective jak1 inhibitor, for treatment of moderate-severe atopic dermatitis: a 12 week, randomized, double blind, placebo controlled phase 2 clinical trial [abstract]. 26th EADV Conference; Geneva, Switzerland .2017
   Google Scholar
• Guttman-Yassky E, Anderson J, APangan A, et al. Primary results from a phase 2b, randomized, placebo-controlled trial of upadacitinib for patients with atopic dermatitis [abstract]. American Academy of Dermatology Annual Meeting; Feb 16–20; San Diego 2018.
   Google Scholar
• Wu NL, Huang DY, Wang LF, et al. Spleen tyrosine kinase mediates EGFR signaling to regulate keratinocyte terminal differentiation. J Invest Dermatol. 2016 Jan;136(1):192–201.
   PubMed Web of Science ®Google Scholar
• Mocsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol. 2010 Jun;10(6):387–402.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Pavel AB, Song T, et al. 559 ASN002 a dual oral inhibitor of JAK/SYK signaling improves clinical outcomes and associated cutaneous inflammation in moderate-to-severe atopic dermatitis patients. J Invest Dermatol. 2018 May 01;138(5, Supplement):S95.
   Web of Science ®Google Scholar
• Hanifin JM, Chan SC, Cheng JB, et al. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. J Invest Dermatol. 1996 Jul;107(1):51–56.
   PubMed Web of Science ®Google Scholar
• Baumer W, Hoppmann J, Rundfeldt C, et al. Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17–26.
   PubMedGoogle Scholar
• Novak N, Bieber T, Leung DY. Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol. 2003 Dec;112(6 Suppl):S128–39.
   PubMedGoogle Scholar
• Jimenez JL, Punzon C, Navarro J, et al. Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Ther. 2001 Nov;299(2):753–759.
   PubMed Web of Science ®Google Scholar
• Wen AY, Sakamoto KM, Miller LS. The role of the transcription factor CREB in immune function. J Immunol. 2010 Dec 1;185(11):6413–6419.
   PubMed Web of Science ®Google Scholar
• Hou S, Guan H, Ricciardi RP. Phosphorylation of serine 337 of NF-kappaB p50 is critical for DNA binding. J Biol Chem. 2003 Nov 14;278(46):45994–45998.
   PubMed Web of Science ®Google Scholar
• Deeks ED, Apremilast: a review in psoriasis and psoriatic arthritis. Drugs. 2015 Aug; 75(12):1393–1403
   PubMed Web of Science ®Google Scholar
• Simpson E, Imafuku S, Poulin Y, et al. A characteristic subset of psoriasis-associated genes is induced by oncostatin-M in reconstituted epidermis. J Invest Dermatol. 2018 Dec; 126(12):2647–57.
   Google Scholar
• Glatzer F, Gschwandtner M, Ehling S, et al. Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J Allergy Clin Immunol. 2013 Dec;132(6):1358–1367.
   PubMed Web of Science ®Google Scholar
• Gutzmer R, Mommert S, Gschwandtner M, et al. The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol. 2009 Mar;123(3):619–625.
   PubMed Web of Science ®Google Scholar
• Ohsawa Y, Hirasawa N. The antagonism of histamine H1 and H4 receptors ameliorates chronic allergic dermatitis via anti-pruritic and anti-inflammatory effects in NC/Nga mice. Allergy. 2012 Aug;67(8):1014–1022.
   PubMed Web of Science ®Google Scholar
• Murata Y, Song M, Kikuchi H, et al. Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. J Dermatol. 2015 Feb;42(2):129–139.
   PubMed Web of Science ®Google Scholar
• Werfel T, Lynch V, Asher A, et al., editors. A phase 2a proof of concept clinical trial to evaluate ZPL-3893787 (ZPL-389), a potent, oral histamine H-4 receptor antagonist for the treatment of moderate to severe atopic dermatitis (AD) in adults. Allergy. 2016 Aug;71:95. NJ, USA: WILEY-BLACKWELL 111 RIVER ST, HOBOKEN 07030-5774.
   Web of Science ®Google Scholar
• Hagermark O, Hokfelt T, Pernow B. Flare and itch induced by substance P in human skin. J Invest Dermatol. 1978 Oct;71(4):233–235.
   PubMed Web of Science ®Google Scholar
• Andoh T, Nagasawa T, Satoh M, et al. Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther. 1998 Sep;286(3):1140–1145.
   PubMed Web of Science ®Google Scholar
• Toyoda M, Nakamura M, Makino T, et al. Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol. 2002 Jul;147(1):71–79.
   PubMed Web of Science ®Google Scholar
• Ohmura T, Hayashi T, Satoh Y, et al. Involvement of substance P in scratching behaviour in an atopic dermatitis model. Eur J Pharmacol. 2004 May 3;491(2–3):191–194.
   PubMed Web of Science ®Google Scholar
• Heitman A, Xiao C, Cho Y, et al. Tradipitant improves worst itch and disease severity in patients with chronic pruritus related to atopic dermatitis [abstract]. J Am Acad Dermatol. 2018;79(3):AB300.
   Web of Science ®Google Scholar
• Menlo Therapeutics announces results from a phase 2 trial of serlopitant for pruritus associated with atopic dermatitis [Internet]. Menlo Therapeutics. 2018 Apr 9; [cited 2018 Jan 4]. Available from: http://www.menlotherapeutics.com/newsroom/menlo-therapeutics-announces-results-from-a-phase-2-trial-of-serlopitant-for-pruritus-associated-with-atopic-dermatitis/
   Google Scholar
• Phan NQ, Bernhard JD, Luger TA, et al. Antipruritic treatment with systemic mu-opioid receptor antagonists: a review. J Am Acad Dermatol. 2010 Oct;63(4):680–688.
   PubMed Web of Science ®Google Scholar
• Phan NQ, Lotts T, Antal A, et al. Systemic kappa opioid receptor agonists in the treatment of chronic pruritus: a literature review. Acta Derm Venereol. 2012 Sep;92(5):555–560.
   PubMed Web of Science ®Google Scholar
• Ko MC, Husbands SM. Effects of atypical kappa-opioid receptor agonists on intrathecal morphine-induced itch and analgesia in primates. J Pharmacol Exp Ther. 2009 Jan;328(1):193–200.
   PubMed Web of Science ®Google Scholar
• Tominaga M, Ogawa H, Takamori K. Possible roles of epidermal opioid systems in pruritus of atopic dermatitis. J Invest Dermatol. 2007 Sep;127(9):2228–2235.
   PubMed Web of Science ®Google Scholar
• Bishop K, Visonneau S, McGuire D, editors. Development of asimadoline, a selective kappa opioid receptor agonist, for the treatment of pruritus. 8th World Congress on Itch (WCI); Nara, Japan; 2015.
   Google Scholar
• Tioga Pharmaceuticals’ asimadoline reduces nighttime itching and improves disease-related quality of life in patients with atopic dermatitis [Internet]. PR Newswire. [Updated 2017 Dec 4; cited 4 Jan 2018]. Available from: https://www.prnewswire.com/news-releases/tioga-pharmaceuticals-asimadoline-reduces-nighttime-itching-and-improves-disease-related-quality-of-life-in-patients-with-atopic-dermatitis-300566114.html
   Google Scholar
• Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr. 2000 Jan;71(1Suppl):367S–72S.
   PubMed Web of Science ®Google Scholar
• Kawashima H, Tateishi N, Shiraishi A, et al. Oral administration of dihomo-gamma-linolenic acid prevents development of atopic dermatitis in NC/Nga mice. Lipids. 2008 Jan;43(1):37–43.
   PubMed Web of Science ®Google Scholar
• Wright S. Atopic dermatitis and essential fatty acids: a biochemical basis for atopy? Acta Derm Venereol Suppl (Stockh). 1985;114:143–145.
   PubMedGoogle Scholar
• Sala-Vila A, Miles EA, Calder PC. Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined. Clin Exp Allergy. 2008 Sep;38(9):1432–1450.
   PubMed Web of Science ®Google Scholar
• Amagai Y, Oida K, Matsuda A, et al. Dihomo-gamma-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC/Tnd mice. J Dermatol Sci. 2015 Jul;79(1):30–37.
   PubMed Web of Science ®Google Scholar
• Desbois AP, Lawlor KC. Antibacterial activity of long-chain polyunsaturated fatty acids against propionibacterium acnes and staphylococcus aureus. Mar Drugs. 2013 Nov 13;11(11):4544–4557.
   PubMed Web of Science ®Google Scholar
• Hamza M, Lebwohl M, Thaci D, et al. Topical DS107 for the treatment of mild-to-moderate atopic dermatitis: results from ADVANTAGE, an 8 week phase 2b randomized, double-blind, vehicle-controlled study [abstract]. Exp Dermatol. 2018 Dec 10;27:37–38.
   Web of Science ®Google Scholar
• Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol. 2017 Jun;139(6):1723–1734.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Dhingra N, Leung DY. New era of biologic therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013 Apr;13(4):549–561.
   PubMed Web of Science ®Google Scholar
• Hirano SA, Murray SB, Harvey VM. Reporting, representation, and subgroup analysis of race and ethnicity in published clinical trials of atopic dermatitis in the United States between 2000 and 2009. Pediatr Dermatol. 2012 Nov-Dec;29(6):749–755.
   PubMed Web of Science ®Google Scholar