{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:32:19Z","timestamp":1790015539347,"version":"4.0.1"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009857","name":"Regeneron Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Am J Clin Dermatol"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1007\/s40257-019-00445-7","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T20:41:40Z","timestamp":1557261700000},"page":"443-456","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":161,"title":["Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2760-0474","authenticated-orcid":false,"given":"Lawrence F.","family":"Eichenfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-3817","authenticated-orcid":false,"given":"Thomas","family":"Bieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-667X","authenticated-orcid":false,"given":"Lisa A.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-7087","authenticated-orcid":false,"given":"Eric L.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamant","family":"Tha\u00e7i","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1249-6993","authenticated-orcid":false,"given":"Marjolein","family":"de Bruin-Weller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-9925","authenticated-orcid":false,"given":"Mette","family":"Deleuran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3686-7805","authenticated-orcid":false,"given":"Jonathan I.","family":"Silverberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Ferrandiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"F\u00f6lster-Holst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil M. H.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Pirozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2334-5717","authenticated-orcid":false,"given":"Bolanle","family":"Akinlade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Yancopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7712-6862","authenticated-orcid":false,"given":"Marius","family":"Ardeleanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"445_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nrd4624","volume":"15","author":"NA Gandhi","year":"2016","unstructured":"Gandhi NA, Bennett BL, Graham NM, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15:35\u201350.","journal-title":"Nat Rev Drug Discov."},{"key":"445_CR2","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.jaip.2014.03.006","volume":"2","author":"T Czarnowicki","year":"2014","unstructured":"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;2:371\u20139.","journal-title":"J Allergy Clin Immunol Pract."},{"key":"445_CR3","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1016\/j.jaip.2017.08.005","volume":"5","author":"M Boguniewicz","year":"2017","unstructured":"Boguniewicz M, Alexis AF, Beck LA, Block J, Eichenfield LF, Fonacier L, et al. Expert perspectives on management of moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and emerging therapies. J Allergy Clin Immunol Pract. 2017;5:1519\u201331.","journal-title":"J Allergy Clin Immunol Pract."},{"key":"445_CR4","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1056\/NEJMra074081","volume":"358","author":"T Bieber","year":"2008","unstructured":"Bieber T. Atopic dermatitis. N Engl J Med. 2008;358:1483\u201394.","journal-title":"N Engl J Med."},{"key":"445_CR5","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1111\/bjd.14566","volume":"175","author":"JE Tott\u00e9","year":"2016","unstructured":"Tott\u00e9 JE, van der Feltz WT, Hennekam M, van Belkum A, van Zuuren EJ, Pasmans SG. Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol. 2016;175:687\u201395.","journal-title":"Br J Dermatol."},{"key":"445_CR6","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.jaci.2009.05.020","volume":"124","author":"LA Beck","year":"2009","unstructured":"Beck LA, Boguniewicz M, Hata T, Schneider LC, Hanifin J, Gallo R, et al. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum. J Allergy Clin Immunol. 2009;124:260\u20139.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR7","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.jaci.2011.02.010","volume":"127","author":"DY Leung","year":"2011","unstructured":"Leung DY, Gao PS, Grigoryev DN, Rafaels NM, Streib JE, Howell MD, et al. Human atopic dermatitis complicated by eczema herpeticum is associated with abnormalities in IFN-\u03b3 response. J Allergy Clin Immunol. 2011;127:965\u201373.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR8","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.jaci.2011.06.003","volume":"128","author":"MD Howell","year":"2011","unstructured":"Howell MD, Gao P, Kim BE, Rafaels NM, Streib JE, Howell MD, et al. The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections. J Allergy Clin Immunol. 2011;128:1006\u201314.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR9","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1016\/j.jaci.2015.06.047","volume":"136","author":"L Gao","year":"2015","unstructured":"Gao L, Bin L, Rafaels NM, Huang L, Potee J, Ruczinski I, et al. Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of atopic dermatitis complicated by eczema herpeticum. J Allergy Clin Immunol. 2015;136:1591\u2013600.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR10","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/jid.2008.259","volume":"129","author":"A De Benedetto","year":"2009","unstructured":"De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA. Atopic dermatitis: a disease caused by innate immune defects? J Investig Dermatol. 2009;129:14\u201330.","journal-title":"J Investig Dermatol."},{"key":"445_CR11","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s12016-016-8548-5","volume":"51","author":"PY Ong","year":"2016","unstructured":"Ong PY, Leung DY. Bacterial and viral infections in atopic dermatitis: a comprehensive review. Clin Rev Allergy Immunol. 2016;51:329\u201337.","journal-title":"Clin Rev Allergy Immunol."},{"key":"445_CR12","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.sder.2008.04.002","volume":"27","author":"TR Hata","year":"2008","unstructured":"Hata TR, Gallo RL. Antimicrobial peptides, skin infections, and atopic dermatitis. Semin Cutan Med Surg. 2008;27:144\u201350.","journal-title":"Semin Cutan Med Surg."},{"key":"445_CR13","doi-asserted-by":"publisher","first-page":"532","DOI":"10.2340\/00015555-1996","volume":"95","author":"LA Salah","year":"2015","unstructured":"Salah LA, Faergemann J. A retrospective analysis of skin bacterial colonisation, susceptibility and resistance in atopic dermatitis and impetigo patients. Acta Derm Venereol. 2015;95:532\u20135.","journal-title":"Acta Derm Venereol."},{"key":"445_CR14","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.antiviral.2013.02.010","volume":"98","author":"DY Leung","year":"2013","unstructured":"Leung DY. Why is eczema herpeticum unexpectedly rare? Antiviral Res. 2013;98:153\u20137.","journal-title":"Antiviral Res."},{"key":"445_CR15","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1093\/cid\/cir952","volume":"54","author":"JL Reed","year":"2012","unstructured":"Reed JL, Scott DE, Bray M. Eczema vaccinatum. Clin Infect Dis. 2012;54:832\u201340.","journal-title":"Clin Infect Dis."},{"key":"445_CR16","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jid.2017.08.039","volume":"138","author":"DY Hsu","year":"2018","unstructured":"Hsu DY, Shinkai K, Silverberg JI. Epidemiology of eczema herpeticum in hospitalized US children: analysis of a nationwide cohort. J Investig Dermatol. 2018;138:265\u201372.","journal-title":"J Investig Dermatol."},{"key":"445_CR17","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.jid.2017.01.030","volume":"137","author":"SM Langan","year":"2017","unstructured":"Langan SM, Abuabara K, Henrickson SE, Hoffstad O, Margolis DJ. Increased risk of cutaneous and systemic infections in atopic dermatitis\u2014a cohort study. J Investig Dermatol. 2017;137:1375\u20137.","journal-title":"J Investig Dermatol."},{"key":"445_CR18","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.anai.2017.10.019","volume":"120","author":"S Narla","year":"2018","unstructured":"Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Ann Allergy Asthma Immunol. 2018;120:66\u201372.","journal-title":"Ann Allergy Asthma Immunol."},{"key":"445_CR19","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/j.jaad.2018.11.028","volume":"80","author":"L Serrano","year":"2018","unstructured":"Serrano L, Patel KR, Silverberg J. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:904\u201312.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR20","doi-asserted-by":"publisher","first-page":"5147","DOI":"10.1073\/pnas.1323896111","volume":"111","author":"LE MacDonald","year":"2014","unstructured":"MacDonald LE, Karow M, Stevens S, Auerbach W, Poueymirou WT, Yasenchak J, et al. Precise and in situ genetic humanization of 6\u00a0Mb of mouse immunoglobulin genes. Proc Natl Acad Sci USA. 2014;111:5147\u201352.","journal-title":"Proc Natl Acad Sci USA"},{"key":"445_CR21","doi-asserted-by":"publisher","first-page":"5153","DOI":"10.1073\/pnas.1324022111","volume":"111","author":"AJ Murphy","year":"2014","unstructured":"Murphy AJ, Macdonald LE, Stevens S, Karow M, Dore AT, Pobursky K, et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci USA. 2014;111:5153\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"445_CR22","unstructured":"DUPIXENT\u00ae (dupilumab) Injection. Package insert. Regeneron Pharmaceuticals, Inc., Tarrytown, NY; Sanofi-Aventis U.S., Bridgewater, NJ; 2019. \n                    https:\/\/www.regeneron.com\/sites\/default\/files\/Dupixent_FPI.pdf\n                    \n                  . Accessed 13 Mar 2019."},{"key":"445_CR23","unstructured":"DUPIXENT\u00ae (dupilumab) Injection. Package insert. Tarrytown, NY, USA: Regeneron Pharmaceuticals, Inc.; Tokyo, Japan: Sanofi K.K."},{"key":"445_CR24","unstructured":"European Medicines Agency. Annex I. Summary of product characteristics [dupilumab]. \n                    http:\/\/www.ema.europa.eu\/documents\/product-information\/dupixent-epar-product-information_en.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0140-6736(16)30307-5","volume":"388","author":"S Wenzel","year":"2016","unstructured":"Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting \u03b22 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388:31\u201344.","journal-title":"Lancet."},{"key":"445_CR26","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","volume":"378","author":"M Castro","year":"2018","unstructured":"Castro M, Corren J, Pavord I, Maspero J, Wenzel S, Rabe K, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486\u201396.","journal-title":"N Engl J Med."},{"key":"445_CR27","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1056\/NEJMoa1804093","volume":"378","author":"K Rabe","year":"2018","unstructured":"Rabe K, Nair P, Brusselle G, Maspero J, Castro M, Sher L, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378:2475\u201385.","journal-title":"N Engl J Med."},{"key":"445_CR28","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1001\/jama.2015.19330","volume":"315","author":"C Bachert","year":"2016","unstructured":"Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315:469\u201379.","journal-title":"JAMA."},{"key":"445_CR29","unstructured":"Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, et al. Dupilumab efficacy and safety in adult patients with active eosinophilic esophagitis: a randomized double-blind placebo-controlled phase 2 trial [Late-breaking abstract 20]. In: World Congress of Gastroenterology at ACG 2017, 13\u201318 Oct, 2017, Orlando, FL."},{"key":"445_CR30","first-page":"5","volume":"23","author":"A Cinats","year":"2018","unstructured":"Cinats A, Heck E, Robertson L. Janus kinase inhibitors: a review of their emerging applications in dermatology. Skin Ther Lett. 2018;23:5\u20139.","journal-title":"Skin Ther Lett."},{"key":"445_CR31","unstructured":"ENBREL\u00ae (etanercept) Injection. Prescribing information. Thousand Oaks, CA: Immunex Corporation\/AMGEN; 2016. \n                    http:\/\/www.pi.amgen.com\/~\/media\/amgen\/repositorysites\/pi-amgen-com\/enbrel\/enbrel_pi.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR32","unstructured":"HUMIRA\u00ae (adalimumab) Injection. Prescribing information. North Chicago, IL: AbbVie, Inc.; 2017. \n                    http:\/\/www.rxabbvie.com\/pdf\/humira.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR33","unstructured":"REMICADE\u00ae (infliximab) Injection. Package insert. Horsham, PA: Janssen Biotech, Inc.; 2015. \n                    http:\/\/www.janssenlabels.com\/package-insert\/product-monograph\/prescribing-information\/REMICADE-pi.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR34","unstructured":"STELARA\u00ae (ustekinumab) Injection. Prescribing information. Horsham, PA: Janssen Biotech, Inc.; 2017. \n                    http:\/\/www.janssenlabels.com\/package-insert\/product-monograph\/prescribing-information\/STELARA-pi.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR35","unstructured":"TREMFYA\u00ae (guselkumab) Injection. Prescribing information. Horsham, PA: Janssen Biotech, Inc.; 2019. \n                    http:\/\/www.janssenlabels.com\/package-insert\/product-monograph\/prescribing-information\/TREMFYA-pi.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR36","unstructured":"CIMZIA\u00ae (certolizumab pegol) Injection. Prescribing Information. Smyrna, GA: ICB, Inc.; 2018. \n                    http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/125160s283lbl.pdf#page=37\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR37","unstructured":"COSENTYX\u00ae (secukinumab) Injection. Prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018. \n                    http:\/\/www.pharma.us.novartis.com\/sites\/www.pharma.us.novartis.com\/files\/cosentyx.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR38","unstructured":"TALTZ\u00ae (ixekizumab) Injection. Prescribing information. Indianapolis, IN: Eli Lilly and Company; 2018. \n                    http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/125521s009lbl.pdf\n                    \n                  . Accessed 10 March 2019."},{"key":"445_CR39","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1093\/rheumatology\/keu172","volume":"53","author":"A Souto","year":"2014","unstructured":"Souto A, Maneiro JR, Salgado E, Carmona L, Gomez-Reino JJ. Risk of tuberculosis in patients with chronic immune-mediated inflammatory diseases treated with biologics and tofacitinib: a systematic review and meta-analysis of randomized controlled trials and long-term extension studies. Rheumatology (Oxford). 2014;53:1872\u201385.","journal-title":"Rheumatology (Oxford)."},{"key":"445_CR40","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jaci.2015.10.023","volume":"137","author":"M Her","year":"2016","unstructured":"Her M, Kavanaugh A. Alterations in immune function with biologic therapies for autoimmune disease. J Allergy Clin Immunol. 2016;137:19\u201327.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR41","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s40257-016-0206-4","volume":"17","author":"AW Armstrong","year":"2016","unstructured":"Armstrong AW, Bukhalo M, Blauvelt A. A clinician\u2019s guide to the diagnosis and treatment of candidiasis in patients with psoriasis. Am J Clin Dermatol. 2016;17:329\u201336.","journal-title":"Am J Clin Dermatol."},{"key":"445_CR42","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.jaad.2017.07.047","volume":"77","author":"AS Dobry","year":"2017","unstructured":"Dobry AS, Quesenberry CP, Ray GT, Geier JL, Asgari MM. Serious infections among a large cohort of subjects with systemically treated psoriasis. J Am Acad Dermatol. 2017;77:838\u201344.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR43","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.jaad.2016.07.039","volume":"76","author":"I Garcia-Doval","year":"2017","unstructured":"Garcia-Doval I, Cohen AD, Cazzaniga S, Feldhamer I, Addis A, Carretero G, et al. Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti-tumor necrosis factor agents versus classic therapies: prospective meta-analysis of Psonet registries. J Am Acad Dermatol. 2017;76:299\u2013308.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR44","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/bjd.15015","volume":"177","author":"DM Saunte","year":"2017","unstructured":"Saunte DM, Mrowietz U, Puig L, Zachariae C. Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management. Br J Dermatol. 2017;177:47\u201362.","journal-title":"Br J Dermatol."},{"key":"445_CR45","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1111\/bjd.15723","volume":"177","author":"KA Papp","year":"2017","unstructured":"Papp KA, Bachelez H, Blauvelt A, Winthrop KL, Romiti R, Ohtsuki M, et al. Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2017;177:1537\u201351.","journal-title":"Br J Dermatol."},{"key":"445_CR46","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1136\/annrheumdis-2015-207841","volume":"74","author":"KL Winthrop","year":"2015","unstructured":"Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, Polgreen P, et al. Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74:2107\u201316.","journal-title":"Ann Rheum Dis."},{"key":"445_CR47","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1056\/NEJMoa1314768","volume":"371","author":"LA Beck","year":"2014","unstructured":"Beck LA, Tha\u00e7i D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130\u20139.","journal-title":"N Engl J Med."},{"key":"445_CR48","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/S0140-6736(15)00388-8","volume":"387","author":"D Tha\u00e7i","year":"2016","unstructured":"Tha\u00e7i D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, 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;387:40\u201352.","journal-title":"Lancet."},{"key":"445_CR49","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1016\/S0140-6736(17)31191-1","volume":"389","author":"A Blauvelt","year":"2017","unstructured":"Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, 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;389:2287\u2013303.","journal-title":"Lancet."},{"key":"445_CR50","doi-asserted-by":"publisher","first-page":"158\u201367.e1","DOI":"10.1016\/j.jaad.2018.07.048","volume":"80","author":"A Blauvelt","year":"2019","unstructured":"Blauvelt A, Simpson EL, Tyring SK, Purcell LA, Shumel B, Petro CD, et al. Dupilumab does not affect correlates of vaccine-induced immunity: a randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis. J Am Acad Dermatol. 2019;80:158\u201367.e1.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR51","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1056\/NEJMoa1610020","volume":"375","author":"EL Simpson","year":"2016","unstructured":"Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335\u201348.","journal-title":"N Engl J Med."},{"key":"445_CR52","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1111\/bjd.16156","volume":"178","author":"M de Bruin-Weller","year":"2018","unstructured":"de Bruin-Weller M, Tha\u00e7i D, Smith CH, Reich K, Cork MJ, Radin A, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAF\u00c9). Br J Dermatol. 2018;178:1083\u2013101.","journal-title":"Br J Dermatol."},{"key":"445_CR53","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1056\/NEJMoa1304048","volume":"368","author":"S Wenzel","year":"2013","unstructured":"Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455\u201366.","journal-title":"N Engl J Med."},{"key":"445_CR54","unstructured":"US FDA. 2000. \n                    http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2000\/50777_Protopic_Medr_P2.pdf\n                    \n                  . Accessed 10 Mar 2019."},{"key":"445_CR55","doi-asserted-by":"publisher","first-page":"e86955","DOI":"10.1172\/jci.insight.86955","volume":"1","author":"IA Myles","year":"2016","unstructured":"Myles IA, Williams KW, Reckhow JD, Jammeh ML, Pincus NB, Sastlalla I, et al. Transplantation of human skin microbiota in models of atopic dermatitis. JCI Insight. 2016;1:e86955.","journal-title":"JCI Insight."},{"key":"445_CR56","doi-asserted-by":"publisher","first-page":"207","DOI":"10.4168\/aair.2018.10.3.207","volume":"10","author":"BE Kim","year":"2018","unstructured":"Kim BE, Leung DYM. Significance of skin barrier dysfunction in atopic dermatitis. Allergy Asthma Immunol Res. 2018;10:207\u201315.","journal-title":"Allergy Asthma Immunol Res."},{"key":"445_CR57","doi-asserted-by":"publisher","first-page":"B7","DOI":"10.1016\/j.jid.2018.06.036","volume":"138","author":"C Callewaert","year":"2018","unstructured":"Callewaert C, Knight R, Nakatsuji T, Kosciolek T, Vrbanac A, Kotol P, et al. Dupilumab-mediated IL-4Ra blockade decreases Staphylococcus aureus colonization and increases microbial diversity in patients with atopic dermatitis [Abstract LB1505]. J Investig Dermatol. 2018;138:B7.","journal-title":"J Investig Dermatol."},{"key":"445_CR58","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.jaad.2017.09.074","volume":"78","author":"S Yu","year":"2018","unstructured":"Yu S, Drucker AM, Lebwohl M, Silverberg JI. A systematic review of the safety and efficacy of systemic corticosteroids in atopic dermatitis. J Am Acad Dermatol. 2018;78:733\u201340.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR59","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.jaad.2010.04.027","volume":"64","author":"IM Haeck","year":"2011","unstructured":"Haeck IM, Knol MJ, Ten Berge O, van Velsen SG, de Bruin-Weller MS, Bruijnzeel-Koomen CA. Enteric-coated mycophenolate sodium versus cyclosporin A as long-term treatment in adult patients with severe atopic dermatitis: a randomized controlled trial. J Am Acad Dermatol. 2011;64:1074\u201384.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR60","first-page":"802","volume":"96","author":"A-L V\u00e9die","year":"2016","unstructured":"V\u00e9die A-L, Ezzedine K, Amazan E, Boralevi F, Milpied B, Ta\u00efeb A, et al. Long-term use of systemic treatments for moderate-to-severe atopic dermatitis in adults: a monocentric retrospective study. Acta Derm Venereol. 2016;96:802\u20136.","journal-title":"Acta Derm Venereol."},{"key":"445_CR61","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.jaci.2011.03.024","volume":"128","author":"ME Schram","year":"2011","unstructured":"Schram ME, Roekevisch E, Leeflang MM, Bos JD, Schmitt J, Spuls PI. A randomized trial of methotrexate vs azathioprine for severe atopic eczema. J Allergy Clin Immunol. 2011;128:353\u20139.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR62","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/bjd.16227","volume":"178","author":"R Bissonnette","year":"2018","unstructured":"Bissonnette R. JAK inhibitors appear to have a bright future in the treatment of atopic dermatitis. Br J Dermatol. 2018;178:321.","journal-title":"Br J Dermatol."},{"key":"445_CR63","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1111\/bjd.15928","volume":"178","author":"AM Drucker","year":"2018","unstructured":"Drucker AM, Eyerich K, de Bruin-Weller MS, Thyssen JP, Spuls PI, Irvine AD, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018;178:768\u201375.","journal-title":"Br J Dermatol."},{"key":"445_CR64","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1159\/000451083","volume":"171","author":"AS Moreno","year":"2016","unstructured":"Moreno AS, McPhee R, Arruda LK, Howell MD. Targeting the T helper 2 inflammatory axis in atopic dermatitis. Int Arch Allergy Immunol. 2016;171:71\u201380.","journal-title":"Int Arch Allergy Immunol."},{"key":"445_CR65","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1111\/bph.13396","volume":"173","author":"N Landolina","year":"2016","unstructured":"Landolina N, Levi-Schaffer F. Monoclonal antibodies: the new magic bullets for allergy: IUPHAR Review 17. Br J Pharmacol. 2016;173:793\u2013803.","journal-title":"Br J Pharmacol."},{"key":"445_CR66","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1016\/j.jaci.2011.09.009","volume":"128","author":"AA Navarini","year":"2011","unstructured":"Navarini AA, French LE, Hofbauer GF. Interrupting IL-6-receptor signaling improves atopic dermatitis but associates with bacterial superinfection. J Allergy Clin Immunol. 2011;128:1128\u201330.","journal-title":"J Allergy Clin Immunol."},{"key":"445_CR67","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1038\/nri2199","volume":"7","author":"RM Anthony","year":"2007","unstructured":"Anthony RM, Rutitzky LI, Urban JF Jr, Stadecker MJ, Gause WC. Protective mechanisms in helminth infection. Nat Rev Immunol. 2007;7:975\u201387.","journal-title":"Nat Rev Immunol."},{"key":"445_CR68","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1046\/j.1365-2567.1998.00412.x","volume":"93","author":"N Ishikawa","year":"1998","unstructured":"Ishikawa N, Goyal PK, Mahida YR, Li KF, Wakelin D. Early cytokine responses during intestinal parasitic infections. Immunology. 1998;93:257\u201363.","journal-title":"Immunology."},{"key":"445_CR69","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.immunol.21.120601.141142","volume":"21","author":"TA Wynn","year":"2003","unstructured":"Wynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425\u201356.","journal-title":"Annu Rev Immunol."},{"key":"445_CR70","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/nri3831","volume":"15","author":"TA Wynn","year":"2015","unstructured":"Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol. 2015;15:271\u201382.","journal-title":"Nat Rev Immunol."},{"key":"445_CR71","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.4049\/jimmunol.0902469","volume":"184","author":"MD Elftman","year":"2010","unstructured":"Elftman MD, Hunzeker JT, Melinger JC, Bonneau RH, Norbury CC, Truckenmiller ME. Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function. J Immunol. 2010;184:1867\u201375.","journal-title":"J Immunol."},{"key":"445_CR72","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.bbi.2009.04.009","volume":"23","author":"Y Chida","year":"2009","unstructured":"Chida Y, Mao X. Does psychosocial stress predict symptomatic herpes simplex virus recurrence? A meta-analytic investigation on prospective studies. Brain Behav Immun. 2009;23:917\u201325.","journal-title":"Brain Behav Immun."},{"key":"445_CR73","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1093\/aje\/kwt241","volume":"179","author":"C Ludema","year":"2014","unstructured":"Ludema C, Cole SR, Poole C, Smith JS, Schoenbach VJ, Wilhelmus KR. Association between unprotected ultraviolet radiation exposure and recurrence of ocular herpes simplex virus. Am J Epidemiol. 2014;179:208\u201315.","journal-title":"Am J Epidemiol."},{"key":"445_CR74","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17869","author":"B Akinlade","year":"2019","unstructured":"Akinlade B, Guttman-Yassky E, de Bruin-Weller M, Simpson EL, Blauvelt A, Cork MJ, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019. \n                    https:\/\/doi.org\/10.1111\/bjd.17869\n                    \n                  \n                           (Epub ahead of print).","journal-title":"Br J Dermatol."},{"key":"445_CR75","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.intimp.2017.11.031","volume":"54","author":"Z Ou","year":"2018","unstructured":"Ou Z, Chen C, Chen A, Yang Y, Zhou W. Adverse events of dupilumab in adults with moderate-to-severe atopic dermatitis: a meta-analysis. Int Immunopharmacol. 2018;54:303\u201310.","journal-title":"Int Immunopharmacol."},{"key":"445_CR76","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jaad.2017.09.052","volume":"78","author":"P Fleming","year":"2018","unstructured":"Fleming P, Drucker AM. Risk of infection in patients with atopic dermatitis treated with dupilumab: a meta-analysis of randomized controlled trials. J Am Acad Dermatol. 2018;78:62\u20139.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR77","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15596.1","author":"PH Gazzinelli-Guimaraes","year":"2018","unstructured":"Gazzinelli-Guimaraes PH, Nutman TB. Helminth parasites and immune regulation. F1000Res. 2018. \n                    https:\/\/doi.org\/10.12688\/f1000research.15596.1\n                    \n                  \n                           (faculty rev 1685).","journal-title":"F1000Res"},{"key":"445_CR78","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.coi.2012.06.003","volume":"24","author":"RM Maizels","year":"2012","unstructured":"Maizels RM, Hewitson JP, Smith KA. Susceptibility and immunity to helminth parasites. Curr Opin Immunol. 2012;24:459\u201366.","journal-title":"Curr Opin Immunol."},{"key":"445_CR79","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.jaad.2016.04.066","volume":"75","author":"ME Gonzalez","year":"2016","unstructured":"Gonzalez ME, Schaffer JV, Orlow SJ, Gao Z, Li H, Alekseyenko AV, et al. Cutaneous microbiome effects of fluticasone proprionate cream and adjunctive bleach baths in childhood atopic dermatitis. J Am Acad Dermatol. 2016;75:481\u201393.","journal-title":"J Am Acad Dermatol."},{"key":"445_CR80","first-page":"268","volume":"2","author":"VK Wong","year":"2003","unstructured":"Wong VK, Della Croce C, Schonfeld S, Mastrangelo AM, Lebwohl M. Use and abuse of topical corticosteroids in infections of the skin and related structures. J Drugs Dermatol. 2003;2:268\u201376.","journal-title":"J Drugs Dermatol."}],"container-title":["American Journal of Clinical Dermatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40257-019-00445-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40257-019-00445-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40257-019-00445-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T23:54:57Z","timestamp":1588722897000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40257-019-00445-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,7]]},"references-count":80,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["445"],"URL":"https:\/\/doi.org\/10.1007\/s40257-019-00445-7","relation":{},"ISSN":["1175-0561","1179-1888"],"issn-type":[{"value":"1175-0561","type":"print"},{"value":"1179-1888","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,7]]},"assertion":[{"value":"7 May 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"All studies were conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Council for Harmonisation guidelines for Good Clinical Practice and applicable regulatory requirements [\u2013]. All patients provided written informed consent before participating in the studies. The studies\u2019 ClinicalTrials.gov identifiers are as follows: NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The study sponsors participated in the study design collection, analysis, and interpretation of data; writing of the report; and the decision to submit the article for publication. Medical writing\/editorial assistance was provided by Vicki Schwartz, PhD, and Manuela Pigors, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"L. F. Eichenfield has received honoraria for consulting services from Almirall, Celgene, Dermira, Dermavant, Eli Lilly and Company, Fort\u00e9 Pharma, Galderma, L\u2019Or\u00e9al, Incyte, MatriSys, Menlo Therapeutics, Otsuka, Novan, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Valeant\/Ortho Dermatologics; and study support (to institution) from Celgene, Dermira, Dermavant, Eli Lilly and Company, Galderma, Incyte, Medimetriks, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Valeant. T. Bieber is a speaker for Almirall, Anacor, Astellas, Celgene, Chugai, Galderma, Janssen-Cilag, L\u2019Or\u00e9al, Novartis, Oxagen, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. L. A. Beck has received honoraria as a consultant and research grants as principal investigator for clinical trials from AbbVie, Pfizer, Realm Therapeutics, and Regeneron Pharmaceuticals, Inc.; has received honoraria as a consultant from AbbVie, Astra-Zeneca, Allakos, Boehringer-Ingelheim, Celgene, Eli Lilly and Company, GSK, Leo Pharma, Novan, Novartis, Realm Therapeutics, Regeneron, Sanofi, and UCB; and is a stockholder in Medtronic and Pfizer. E. L. Simpson has received honoraria for consulting services from AbbVie, Anacor, Celgene, Dermira Pharmaceutical Co., Eli Lilly and Company, Galderma, Genentech, Inc., GSK, LEO Pharma, Menlo Therapeutics, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Valeant Pharmaceutical Co.; and has received study support from Anacor, Eli Lilly and Company, GSK, MedImmune, Novartis, Regeneron Pharmaceuticals, Inc., Roivant Sciences, Tioga Pharmaceuticals, Inc., and Vanda Pharmaceuticals, Inc. D. Tha\u00e7i has received research support from AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Celgene, Dignity, Eli Lilly and Company, GSK, Janssen-Cilag, LEO Pharma, MSD, Novartis, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sandoz, and Sanofi; received honoraria and is an independent advisor for AbbVie, Celgene, Janssen, La Roche-Posay, LEO Pharma, Medac, Novartis, Pfizer, Inc., Sun Pharma, and UCB; received honoraria and is a consultant for AbbVie, Celgene, Dignity, Gal\u00e1pagos, Novartis, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sanofi, and UCB; and received honoraria and is an advisory board member for AbbVie, Amgen, Celgene, Eli Lilly and Company, GSK, Janssen, LEO Pharma, Mundipharma, Novartis, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sandoz, Sanofi, and UCB. M. de Bruin-Weller is a principal investigator, advisory board member, and consultant for Regeneron Pharmaceuticals, Inc., and Sanofi Genzyme; and a principal investigator and advisory board member for AbbVie. M. Deleuran has received research support, consulting\/advisory board agreements, and\/or honoraria for lecturing from AbbVie, Eli Lilly and Company, LEO Pharma, Meda, Pierre Fabre, Regeneron Pharmaceuticals, Inc., and Sanofi. J. I. Silverberg has received honoraria for advisory board participation, as a speaker, and for consultancy from AbbVie, Eli Lilly and Company, Galderma, GSK, Kiniksa, LEO Pharma, Menlo Therapeutics, Pfizer, Realm Therapeutics, Regeneron Pharmaceuticals, Inc., Roivant, and Sanofi; and research grants from GSK, Regeneron Pharmaceuticals, Inc., and Sanofi. C. Ferrandiz is a principal investigator in clinical trials for AbbVie, Sanofi, LEO Pharma; and an advisory board participant for Sanofi. R. F\u00f6lster-Holst is an investigator for studies, speaker, and consultant for Astellas, Almirall Hermal, Beiersdorf, Johnson & Johnson, La Roche-Posay, LEO Pharma, Neubourg Skin Care GmbH, Novartis, Pierre Fabre, Procter & Gamble, and Regeneron Pharmaceuticals, Inc. Z. Chen, N.M.H. Graham, B. Akinlade, G.D. Yancopoulos, and M. Ardeleanu are employees of and shareholders in Regeneron Pharmaceuticals, Inc. G. Pirozzi is an employee of and may hold stock and\/or stock options in Sanofi.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}