A Literature Review of Real-World Effectiveness and Safety of Dupilumab for Atopic Dermatitis

Masahiro Kamata, Yayoi Tada, Masahiro Kamata, Yayoi Tada

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with pruritus, characterized by recurrent eczema with exacerbations and remissions. AD impairs patients' QOL and places a heavy burden on patients. Recently, dupilumab, an anti-IL-4Rα antibody, was approved for the treatment of patients with moderate-to-severe AD who are refractory to topical agents and/or conventional systemic therapy. Clinical trials of dupilumab for AD demonstrated high efficacy and tolerable safety profiles. Furthermore, real-world evidence of dupilumab for AD is accumulating. Most of these data show favorable effectiveness and safety profile; however, they also clarified issues, including conjunctivitis and facial redness. There are still a certain number of patients with significant failure. In this article, we review real-world evidence of dupilumab for AD, identify concerns specific to dupilumab, and discuss unmet needs and issues to be addressed in the future.

Keywords: AA, alopecia areata; AD, atopic dermatitis; CsA, cyclosporin A; EASI, Eczema Area and Severity Index; HSV, herpes simplex virus; IGA, Investigator’s Global Assessment; LDH, lactate dehydrogenase; TCS, topical corticosteroid; Th, T helper type; q2w, every other week; qw, weekly.

© 2021 The Authors.

References

    1. Achten R., Bakker D., Ariens L., Lans A., Thijs J., van der Schaft J., et al. Long-term follow-up and treatment outcomes of conjunctivitis during dupilumab treatment in patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol Pract. 2021;9:1389–1392.e2.
    1. Akinlade B., Guttman-Yassky E., de Bruin-Weller M., Simpson E.L., Blauvelt A., Cork M.J., et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019;181:459–473.
    1. Albader S.S., Alharbi A.A., Alenezi R.F., Alsaif F.M. Dupilumab side effect in a patient with atopic dermatitis: a case report study. Biologics. 2019;13:79–82.
    1. Alexis A.F., Rendon M., Silverberg J.I., Pariser D.M., Lockshin B., Griffiths C.E., et al. Efficacy of dupilumab in different racial subgroups of adults with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials. J Drugs Dermatol. 2019;18:804–813.
    1. Andersen Y.M., Egeberg A., Gislason G.H., Skov L., Thyssen J.P. Autoimmune diseases in adults with atopic dermatitis. J Am Acad Dermatol. 2017;76:274–280.e1.
    1. Ariëns L.F.M., van der Schaft J., Bakker D.S., Balak D., Romeijn M.L.E., Kouwenhoven T., et al. Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients: first clinical and biomarker results from the BioDay registry. Allergy. 2020;75:116–126.
    1. Ariëns L.F.M., van der Schaft J., Spekhorst L.S., Bakker D.S., Romeijn G.L.E., Kouwenhoven T.A., et al. Dupilumab shows long-term effectiveness in a large cohort of treatment-refractory atopic dermatitis patients in daily practice: 52-week results from the Dutch BioDay registry. J Am Acad Dermatol. 2021;84:1000–1009.
    1. Arima K., Gupta S., Gadkari A., Hiragun T., Kono T., Katayama I., et al. Burden of atopic dermatitis in Japanese adults: analysis of data from the 2013 National Health and Wellness Survey. J Dermatol. 2018;45:390–396.
    1. Armario-Hita J.C., Pereyra-Rodriguez J., Silvestre J.F., Ruiz-Villaverde R., Valero A., Izu-Belloso R., et al. Treatment of moderate-to-severe atopic dermatitis with dupilumab in real clinical practice: a multicentre, retrospective case series. Br J Dermatol. 2019;181:1072–1074.
    1. Bachert C., Mannent L., Naclerio R.M., Mullol J., Ferguson B.J., 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;315:469–479.
    1. Bakker D.S., Ariens L.F.M., van Luijk C., van der Schaft J., Thijs J.L., Schuttelaar M.L.A., et al. Goblet cell scarcity and conjunctival inflammation during treatment with dupilumab in patients with atopic dermatitis. Br J Dermatol. 2019;180:1248–1249.
    1. Bangert C., Rindler K., Krausgruber T., Alkon N., Thaler F.M., Kurz H., et al. Persistence of mature dendritic cells, TH2A, and Tc2 cells characterize clinically resolved atopic dermatitis under IL-4Rα blockade. Sci Immunol. 2021;6
    1. Barnes A.C., Blandford A.D., Perry J.D. Cicatricial ectropion in a patient treated with dupilumab. Am J Ophthalmol Case Rep. 2017;7:120–122.
    1. Barnett B.P., Afshari N.A. Dupilumab-associated mucin deficiency (DAMD) [published correction appears in Transl Vis Sci Technol 2020;9:21] Transl Vis Sci Technol. 2020;9:29.
    1. Beck L.A., Thaçi D., Deleuran M., Blauvelt A., Bissonnette R., de Bruin-Weller M., et al. Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2020;21:567–577.
    1. Beck L.A., Thaçi D., Deleuran M., de Bruin-Weller M., Chen Z., Khokhar F.A., et al. Laboratory safety of dupilumab for up to 3 years in adults with moderate-to-severe atopic dermatitis: results from an open-label extension study. J Dermatolog Treat. 2021:1–9.
    1. Bieber T., Simpson E.L., Silverberg J.I., Thaçi D., Paul C., Pink A.E., et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384:1101–1112.
    1. Bieber T., Thyssen J.P., Reich K., Simpson E.L., Katoh N., Torrelo A., et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J Eur Acad Dermatol Venereol. 2021;35:476–485.
    1. Blauvelt A., de Bruin-Weller M., Gooderham M., Cather J.C., 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;389:2287–2303.
    1. Boguniewicz M., Beck L.A., Sher L., Guttman-Yassky E., Thaçi D., Blauvelt A., et al. Dupilumab improves asthma and sinonasal outcomes in adults with moderate to severe atopic dermatitis. J Allergy Clin Immunol Pract. 2021;9:1212–1223.e6.
    1. Bohner A., Topham C., Strunck J., Haynes D., Brazil M., Clements J., et al. Dupilumab-associated ocular surface disease: clinical characteristics, treatment, and follow-up. Cornea. 2021;40:584–589.
    1. Bridgewood C., Sharif K., Freeston J., Saleem B., Russell T., Watad A., et al. Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy. Rheumatology (Oxford) 2021;60:2461–2466.
    1. Carrascosa J.M. Immunogenicity in biologic therapy: implications for dermatology. Actas Dermosifiliogr. 2013;104:471–479.
    1. Castro M., Corren J., Pavord I.D., Maspero J., Wenzel S., Rabe K.F., et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486–2496.
    1. Chiba T., Nagai T., Osada S.I., Manabe M. Diagnosis of mycosis fungoides following administration of dupilumab for misdiagnosed atopic dermatitis. Acta Derm Venereol. 2019;99:818–819.
    1. Chovatiya R., Lei D., Ahmed A., Chavda R., Gabriel S., Silverberg J.I. Clinical phenotyping of atopic dermatitis using combined itch and lesional severity: a prospective observational study. Ann Allergy Asthma Immunol. 2021;127:83–90.e2.
    1. Cork M.J., Eckert L., Simpson E.L., Armstrong A., Barbarot S., Puig L., et al. Dupilumab improves patient-reported symptoms of atopic dermatitis, symptoms of anxiety and depression, and health-related quality of life in moderate-to-severe atopic dermatitis: analysis of pooled data from the randomized trials SOLO 1 and SOLO 2. J Dermatolog Treat. 2020;31:606–614.
    1. Cork M.J., Thaçi D., Eichenfield L.F., Arkwright P.D., Hultsch T., Davis J.D., et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol. 2020;182:85–96.
    1. Cork M.J., Thaçi D., Eichenfield L.F., Arkwright P.D., Sun X., Chen Z., et al. Dupilumab provides favourable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled severe atopic dermatitis: results from an open-label phase IIa study and subsequent phase III open-label extension study. Br J Dermatol. 2021;184:857–870.
    1. Cramer J.A., Roy A., Burrell A., Fairchild C.J., Fuldeore M.J., Ollendorf D.A., et al. Medication compliance and persistence: terminology and definitions. Value Health. 2008;11:44–47.
    1. Dal Bello G., Maurelli M., Schena D., Girolomoni G., Gisondi P. Drug survival of dupilumab compared to cyclosporin in moderate-to-severe atopic dermatitis patients. Dermatol Ther. 2020;33:e13979.
    1. de Beer F.S.A., Bakker D.S., Haeck I., Ariens L., van der Schaft J., van Dijk M.R., et al. Dupilumab facial redness: positive effect of itraconazole. JAAD Case Rep. 2019;5:888–891.
    1. de Bruin-Weller M., Graham N.M.H., Pirozzi G., Shumel B. Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with demodex and increased interleukin-17 levels?: reply from the authors. Br J Dermatol. 2018;178:1220–1221.
    1. de Bruin-Weller M., Thaçi D., Smith C.H., Reich K., Cork M.J., 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 CAFÉ) Br J Dermatol. 2018;178:1083–1101.
    1. de Wijs L.E.M., Bosma A.L., Erler N.S., Hollestein L.M., Gerbens L.A.A., Middelkamp-Hup M.A., et al. Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data. Br J Dermatol. 2020;182:418–426.
    1. de Wijs L.E.M., Nguyen N.T., Kunkeler A.C.M., Nijsten T., Damman J., Hijnen D.J. Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series. Br J Dermatol. 2020;183:745–749.
    1. de Wijs L.E.M., van der Waa J.D., de Jong P.H.P., Hijnen D.J. Acute arthritis and arthralgia as an adverse drug reaction to dupilumab. Clin Exp Dermatol. 2020;45:262–263.
    1. Deleuran M., Thaçi D., Beck L.A., de Bruin-Weller M., Blauvelt A., Forman S., et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J Am Acad Dermatol. 2020;82:377–388.
    1. Eckert L., Gupta S., Gadkari A., Mahajan P., Gelfand J.M. Burden of illness in adults with atopic dermatitis: analysis of National Health and Wellness Survey data from France, Germany, Italy, Spain, and the United Kingdom. J Am Acad Dermatol. 2019;81:187–195.
    1. Faiz S., Giovannelli J., Podevin C., Jachiet M., Bouaziz J.D., Reguiai Z., et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J Am Acad Dermatol. 2019;81:143–151.
    1. Fargnoli M.C., Esposito M., Ferrucci S., Girolomoni G., Offidani A., Patrizi A., et al. A 48-week update of a multicentre real-life experience of dupilumab in adult patients with moderate-to-severe atopic dermatitis [e-pub ahead of print] J Dermatol Treat. 2020 doi: 10.1080/09546634.2020.1773379. (accessed 8 August, 2021)
    1. Fargnoli M.C., Esposito M., Ferrucci S., Girolomoni G., Offidani A., Patrizi A., et al. Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis. J Dermatol Treat. 2019;32:507–513.
    1. Ferreira S., Torres T. Conjunctivitis in patients with atopic dermatitis treated with dupilumab. Drugs Context. 2020;9 2020–2–3.
    1. Ferrucci S., Casazza G., Angileri L., Tavecchio S., Germiniasi F., Berti E., et al. Clinical response and quality of life in patients with severe atopic dermatitis treated with dupilumab: a single-center real-life experience. J Clin Med. 2020;9:791.
    1. Fleming P., Drucker A.M. Risk of infection in patients with atopic dermatitis treated with dupilumab: a meta-analysis of randomized controlled trials. J Am Acad Dermatol. 2018;78:62–69.e1.
    1. Fowler E., Silverberg J.I., Fox J.D., Yosipovitch G. Psoriasiform dermatitis after initiation of treatment with dupilumab for atopic dermatitis. Dermatitis. 2019;30:234–236.
    1. Franzen-Röhl E., Schepis D., Atterfelt F., Franck K., Wikström A., Liljeqvist J.Å., et al. Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences. Sex Transm Infect. 2017;93:169–174.
    1. Fujishima H., Takeuchi T., Shinozaki N., Saito I., Tsubota K. Measurement of IL-4 in tears of patients with seasonal allergic conjunctivitis and vernal keratoconjunctivitis. Clin Exp Immunol. 1995;102:395–398.
    1. Gooderham M., McDonald J., Papp K. Diagnosis and management of conjunctivitis for the dermatologist. J Cutan Med Surg. 2018;22:200–206.
    1. Guttman-Yassky E., Bissonnette R., Ungar B., Suárez-Fariñas M., Ardeleanu M., Esaki H., et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143:155–172.
    1. Halling A.S., Loft N., Silverberg J.I., Guttman-Yassky E., Thyssen J.P. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am Acad Dermatol. 2021;84:139–147.
    1. Harada K., Irisawa R., Ito T., Uchiyama M., Tsuboi R. The effectiveness of dupilumab in patients with alopecia areata who have atopic dermatitis: a case series of seven patients. Br J Dermatol. 2020;183:396–397.
    1. Heibel H.D., Hendricks A.J., Foshee J.P., Shi V.Y. Rosacea associated with dupilumab therapy. J Dermatolog Treat. 2021;32:114–116.
    1. Herz S., Petri M., Sondermann W. New alcohol flushing in a patient with atopic dermatitis under therapy with dupilumab. Dermatol Ther. 2019;32:e12762.
    1. Hirano I., Dellon E.S., Hamilton J.D., Collins M.H., Peterson K., Chehade M., et al. Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis. Gastroenterology. 2020;158:111–122.e10.
    1. Howell M.D., Wollenberg A., Gallo R.L., Flaig M., Streib J.E., Wong C., et al. Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006;117:836–841.
    1. Igelman S.J., Na C., Simpson E.L. Alcohol-induced facial flushing in a patient with atopic dermatitis treated with dupilumab. JAAD Case Rep. 2020;6:139–140.
    1. Ishibashi M., Honda T., Tabuchi Y., Kabashima K. Polyenthesitis during treatment with dupilumab for atopic dermatitis. J Eur Acad Dermatol Venereol. 2020;34:e319–e321.
    1. Ito M., Kamata M., Uchida H., Nagata M., Fukaya S., Hayashi K., et al. Introduction of self-injection increases compliance with dupilumab administration in adult patients with atopic dermatitis: a single-center retrospective study. JAAD Int. 2020;1:91–92.
    1. Jahn E.M., Schneider C.K. How to systematically evaluate immunogenicity of therapeutic proteins - regulatory considerations. N Biotechnol. 2009;25:280–286.
    1. Jang D.H., Heo S.J., Jung H.J., Park M.Y., Seo S.J., Ahn J. Retrospective study of dupilumab treatment for moderate to severe atopic dermatitis in Korea: efficacy and safety of dupilumab in real-world practice. J Clin Med. 2020;9:1982.
    1. Jo C.E., Finstad A., Georgakopoulos J.R., Piguet V., Yeung J., Drucker A.M. Facial and neck erythema associated with dupilumab treatment: a systematic review. J Am Acad Dermatol. 2021;84:1339–1347.
    1. Jo C.E., Georgakopoulos J.R., Ladda M., Ighani A., Mufti A., Drucker A.M., et al. Evaluation of long-term efficacy, safety, and reasons for discontinuation of dupilumab for moderate to severe atopic dermatitis in clinical practice: a retrospective cohort study. J Am Acad Dermatol. 2020;82:1530–1532.
    1. Jo C.E., Georgakopoulos J.R., Ladda M., Ighani A., Mufti A., Drucker A.M., et al. Short-term evaluation of the real-world efficacy and safety of dupilumab for the treatment of moderate-to-severe atopic dermatitis: a Canadian multicenter retrospective cohort study [Formula: see text] J Cutan Med Surg. 2020;24:468–473.
    1. Kanda N., Koto M., Hoashi T., Saeki H. Case of alopecia areata during dupilumab treatment for atopic dermatitis. J Dermatol. 2019;46:e332–e333.
    1. Kato A., Kamata M., Ito M., Uchida H., Nagata M., Fukaya S., et al. Higher baseline serum lactate dehydrogenase level is associated with poor effectiveness of dupilumab in the long term in patients with atopic dermatitis. J Dermatol. 2020;47:1013–1019.
    1. Katoh N., Kataoka Y., Saeki H., Hide M., Kabashima K., Etoh T., et al. Efficacy and safety of dupilumab in Japanese adults with moderate-to-severe atopic dermatitis: a subanalysis of three clinical trials. Br J Dermatol. 2020;183:39–51.
    1. Kim B.E., Bin L., Ye Y.M., Ramamoorthy P., Leung D.Y.M. IL-25 enhances HSV-1 replication by inhibiting filaggrin expression, and acts synergistically with Th2 cytokines to enhance HSV-1 replication. J Invest Dermatol. 2013;133:2678–2685.
    1. Kim N.S., Maliyar K., Oliveira L., O'Toole A., Gooderham M.J. Real-world experience of dupilumab in the treatment of moderate-to-severe atopic dermatitis. Int J Dermatol. 2020;59:e361–e363.
    1. Komaki R., Miyagaki T., Nakajima K., Mitsuishi S., Kishi A., Miyano K., et al. Arthritis and enthesitis during dupilumab therapy completely remitted by celecoxib. J Dermatol. 2021;48:e279–e280.
    1. Kreeshan F.C., Al-Janabi A., Warren R.B., Hunter H.J.A. Real-world experience and laboratory monitoring of dupilumab in patients with moderate to severe atopic dermatitis in a tertiary centre. Dermatol Ther (Heidelb) 2021;11:149–160.
    1. Langan S.M., Abuabara K., Henrickson S.E., Hoffstad O., Margolis D.J. Increased risk of cutaneous and systemic infections in atopic dermatitis-a cohort study. J Invest Dermatol. 2017;137:1375–1377.
    1. Lazaridou I., Ram-Wolff C., Bouaziz J.D., Bégon E., Battistella M., Rivet J., et al. Dupilumab treatment in two patients with cutaneous T-cell lymphomas. Acta Derm Venereol. 2020;100
    1. Li G., Berkenstock M., Soiberman U. Corneal ulceration associated with dupilumab use in a patient with atopic dermatitis. Am J Ophthalmol Case Rep. 2020;19:100848.
    1. Liberman P., Shifera A.S., Berkenstock M. Dupilumab-associated conjunctivitis in patients with atopic dermatitis. Cornea. 2020;39:784–786.
    1. Maloney N.J., Worswick S., Cheng K. Development of alopecia in patients treated with dupilumab. Dermatol Ther. 2019;32:e12869.
    1. Marks D.H., Mesinkovska N., Senna M.M. Cause or cure? Review of dupilumab and alopecia areata [e-pub ahead of print] J Am Acad Dermatol. 2019 doi: 10.1016/j.jaad.2019.06.010. (accessed 8 August, 2021)
    1. Masson Regnault M., Konstantinou M.P., Khemis A., Poulin Y., Bourcier M., Amelot F., et al. Early relapse of psoriasis after stopping brodalumab: a retrospective cohort study in 77 patients. J Eur Acad Dermatol Venereol. 2017;31:1491–1496.
    1. Matsutani M., Imai Y., Inoue Y., Hosotani Y., Kusakabe M., Natsuaki M., et al. Real-world use of dupilumab for 53 patients with atopic dermatitis in Japan. J Cutan Immunol Allergy. 2020;3:35–36.
    1. Mohan G.C., Silverberg J.I. Association of vitiligo and alopecia areata with atopic dermatitis: a systematic review and meta-analysis. JAMA Dermatol. 2015;151:522–528.
    1. Nahum Y., Mimouni M., Livny E., Bahar I., Hodak E., Leshem Y.A. Dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis: clinical presentation, risk factors for development and outcomes of treatment with tacrolimus ointment. Br J Ophthalmol. 2020;104:776–779.
    1. Nakahara T., Izuhara K., Onozuka D., Nunomura S., Tamagawa-Mineoka R., Masuda K., et al. Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: a study protocol. Medicine (Baltimore) 2020;99:e22043.
    1. Nakanishi M., Tamagawa-Mineoka R., Arakawa Y., Masuda K., Katoh N. Dupilumab-resistant facial erythema - dermoscopic, histological and clinical findings of three patients. Allergol Int. 2021;70:156–158.
    1. Napolitano M., Caiazzo G., Fabbrocini G., Balato A., Di Caprio R., Scala E., et al. Increased expression of interleukin-23A in lesional skin of patients with atopic dermatitis with psoriasiform reaction during dupilumab treatment. Br J Dermatol. 2021;184:341–343.
    1. Napolitano M., Scalvenzi M., Fabbrocini G., Cinelli E., Patruno C. Occurrence of psoriasiform eruption during dupilumab therapy for adult atopic dermatitis: a case series. Dermatol Ther. 2019;32:e13142.
    1. Nettis E., Bonzano L., Patella V., Detoraki A., Trerotoli P., Lombardo C., et al. Dupilumab-associated conjunctivitis in patients with atopic dermatitis: a multicenter real-life experience. J Investig Allergol Clin Immunol. 2020;30:201–204.
    1. Nettis E., Ferrucci S.M., Ortoncelli M., Pellacani G., Foti C., Di Leo E., et al. Use of dupilumab for 543 adult patients with moderate-to-severe atopic dermatitis: a multicenter, retrospective study [e-pub ahead of print] J Investig Allergol Clin Immunol. 2020 doi: 10.18176/jiaci.0641. (accessed 8 August, 2021)
    1. Nettis E., Patella V., Lombardo C., Detoraki A., Macchia L., Di Leo E., et al. Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis. Allergy. 2020;75:2653–2661.
    1. Newsom M., Hrin M.L., Hamid R.N., Strowd L.C., Ahn C., Jorizzo J.L., et al. Two cases of mycosis fungoides diagnosed after treatment non-response to dupilumab. Dermatol Online J. 2021;27:13030.
    1. Noda S., Suárez-Fariñas M., Ungar B., Kim S.J., de Guzman Strong C., Xu H., et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015;136:1254–1264.
    1. Okiyama N., Nakamura Y., Ishitsuka Y., Inoue S., Kubota N., Saito A., et al. Successful topical treatment with ketoconazole for facial rashes refractory to dupilumab in patients with atopic dermatitis: case reports. J Eur Acad Dermatol Venereol. 2020;34:e474–e476.
    1. Olesen C.M., Holm J.G., Nørreslet L.B., Serup J.V., Thomsen S.F., Agner T. Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre. J Eur Acad Dermatol Venereol. 2019;33:1562–1568.
    1. Paller A.S., Siegfried E.C., Thaçi D., Wollenberg A., Cork M.J., Arkwright P.D., et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial [published correction appears in J Am Acad Dermatol 2021;84:230] J Am Acad Dermatol. 2020;83:1282–1293.
    1. Patruno C., Fabbrocini G., Longo G., Argenziano G., Ferrucci S.M., Stingeni L., et al. Effectiveness and safety of long-term dupilumab treatment in elderly patients with atopic dermatitis: a multicenter real-life observational study. Am J Clin Dermatol. 2021;22:581–586.
    1. Patruno C., Napolitano M., Argenziano G., Peris K., Ortoncelli M., Girolomoni G., et al. Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study. J Eur Acad Dermatol Venereol. 2021;35:958–964.
    1. Paulose S.A., Sherman S.W., Dagi Glass L.R., Suh L.H. Dupilumab-associated blepharoconjunctivitis. Am J Ophthalmol Case Rep. 2019;16:100550.
    1. Popiela M.Z., Barbara R., Turnbull A.M.J., Corden E., Martinez-Falero B.S., O’Driscoll D., et al. Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae [e-pub ahead of print] Eye (Lond) 2021 doi: 10.1038/s41433-020-01379-9. (accessed 8 August, 2021)
    1. Quint T., Brunner P.M., Sinz C., Steiner I., Ristl R., Vigl K., et al. Dupilumab for the treatment of atopic dermatitis in an Austrian cohort-real-life data shows rosacea-like folliculitis. J Clin Med. 2020;9:1241.
    1. Rabe K.F., Nair P., Brusselle G., Maspero J.F., Castro M., Sher L., et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378:2475–2485.
    1. Reich K., Teixeira H.D., de Bruin-Weller M., Bieber T., Soong W., Kabashima K., et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet 2021;397:2336] Lancet. 2021;397:2169–2181.
    1. Renert-Yuval Y., Guttman-Yassky E. A novel therapeutic paradigm for patients with extensive alopecia areata. Expert Opin Biol Ther. 2016;16:1005–1014.
    1. Ribero S., Giura M.T., Viola R., Ramondetta A., Siliquini N., Cardone P., et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in adult cohort: a real-life Italian tertiary centre experience. J Eur Acad Dermatol Venereol. 2020;34:e380–e383.
    1. Ruiz-Villaverde R., Dominguez-Cruz J., Armario-Hita J.C., Martinez-Pilar L., Alcantara-Luna S., Pereyra-Rodriguez J.J. Dupilumab: short-term effectiveness and security in real clinical practice - a retrospective multicentric study. J Eur Acad Dermatol Venereol. 2019;33:e21–e22.
    1. Sachdeva M., Witol A., Mufti A., Maliyar K., Yeung J. Alopecia areata related paradoxical reactions in patients on dupilumab therapy: a systematic review [published correction appears in J Cutan Med Surg 2021;25:464] J Cutan Med Surg. 2021;25:451–452.
    1. Schaeverbeke T., Truchetet M.E., Kostine M., Barnetche T., Bannwarth B., Richez C. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatolpgy (Oxford) 2016;55:210–220.
    1. Schrom K.P., Kobs A., Nedorost S. Clinical psoriasiform dermatitis following dupilumab use for autoeczematization secondary to chronic stasis dermatitis. Cureus. 2020;12:e7831.
    1. Sears A.V., Woolf R.T., Gribaleva E., Abdelrahman W., Robbie S., Menon B., et al. Real-world effectiveness and tolerability of dupilumab in adult atopic dermatitis: a single-centre, prospective 1-year observational cohort study of the first 100 patients treated. Br J Dermatol. 2021;184:755–757.
    1. Seok S.H., An J.H., Shin J.U., Lee H.J., Kim D.H., Yoon M.S., et al. Facial redness in atopic dermatitis patients treated with dupilumab: a case series. Allergy Asthma Immunol Res. 2020;12:1063–1065.
    1. Silverberg J.I. Comorbidities and the impact of atopic dermatitis. Ann Allergy Asthma Immunol. 2019;123:144–151.
    1. Silverberg J.I. Atopic dermatitis in adults. Med Clin North Am. 2020;104:157–176.
    1. Silverberg J.I., Guttman-Yassky E., Gadkari A., Kuznik A., Mallya U.G., Mastey V., et al. Real-world persistence with dupilumab among adults with atopic dermatitis. Ann Allergy Asthma Immunol. 2021;126:40–45.
    1. Silverberg J.I., Simpson E.L., Guttman-Yassky E., Cork M.J., de Bruin-Weller M., Yosipovitch G., et al. Dupilumab significantly modulates pain and discomfort in patients with atopic dermatitis: a post hoc analysis of 5 randomized clinical trials [e-pub ahead of print] Dermatitis. 2020 doi: 10.1097/DER.0000000000000698. (accessed 8 August, 2021)
    1. Silverberg J.I., Thyssen J.P., Fahrbach K., Mickle K., Cappelleri J.C., Romero W., et al. Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis [e-pub ahead of print] J Eur Acad Dermatol Venereol. 2021 doi: 10.1111/jdv.17351. (accessed 8 August, 2021)
    1. Simpson E.L. Comorbidity in atopic dermatitis. Curr Dermatol Rep. 2012;1:29–38.
    1. Simpson E.L., Bieber T., Eckert L., Wu R., Ardeleanu M., Graham N.M., et al. Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol. 2016;74:491–498.
    1. Simpson E.L., Bieber T., Guttman-Yassky E., Beck L.A., Blauvelt A., Cork M.J., et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335–2348.
    1. Simpson E.L., Paller A.S., Siegfried E.C., Boguniewicz M., Sher L., Gooderham M.J., et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis: a phase 3 randomized clinical trial. JAMA Dermatol. 2020;156:44–56.
    1. Sims J.T., Chang C.Y., Higgs R.E., Engle S.M., Liu Y., Sissons S.E., et al. Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate-to-severe disease [e-pub ahead of print] Exp Dermatol. 2021 doi: 10.1111/exd.14389. (accessed 8 August, 2021)
    1. Soria A., Du-Thanh A., Seneschal J., Jachiet M., Staumont-Sallé D., Barbarot S., et al. Development or exacerbation of head and neck dermatitis in patients treated for atopic dermatitis with dupilumab. JAMA Dermatol. 2019;155:1312–1315.
    1. Ständer S., Trense Y., Thaçi D., Ludwig R.J. Alopecia areata development in atopic dermatitis patients treated with dupilumab. J Eur Acad Dermatol Venereol. 2020;34:e612–e613.
    1. Stout M., Silverberg J.I. Variable impact of dupilumab on patch testing results and allergic contact dermatitis in adults with atopic dermatitis. J Am Acad Dermatol. 2019;81:157–162.
    1. Suresh R., Murase J.E. The role of expanded series patch testing in identifying causality of residual facial dermatitis following initiation of dupilumab therapy. JAAD Case Rep. 2018;4:899–904.
    1. Tauber M., Apoil P.A., Richet C., Laurent J., De Bonnecaze G., Mouchon E., et al. Effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real-life practice. Br J Dermatol. 2019;180:1551–1552.
    1. Tavecchio S., Angileri L., Pozzo Giuffrida F., Germiniasi F., Marzano A.V., Ferrucci S. Efficacy of dupilumab on different phenotypes of atopic dermatitis: one-year experience of 221 patients. J Clin Med. 2020;9:2684.
    1. Thaçi D., Simpson E.L., Beck L.A., 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;387:40–52.
    1. Thaçi D., L Simpson E., Deleuran M., Kataoka Y., Chen Z., Gadkari A., et al. Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 AND LIBERTY AD SOLO 2) J Dermatol Sci. 2019;94:266–275.
    1. Thyssen J.P., Toft P.B., Halling-Overgaard A.S., Gislason G.H., Skov L., Egeberg A. Incidence, prevalence, and risk of selected ocular disease in adults with atopic dermatitis. J Am Acad Dermatol. 2017;77:280–286.e1.
    1. Touhouche A.T., Cassagne M., Bérard E., Giordano-Labadie F., Didier A., Fournié P., et al. Incidence and risk factors for dupilumab associated ocular adverse events: a real-life prospective study. J Eur Acad Dermatol Venereol. 2021;35:172–179.
    1. Treister A.D., Kraff-Cooper C., Lio P.A. Risk factors for dupilumab-associated conjunctivitis in patients with atopic dermatitis. JAMA Dermatol. 2018;154:1208–1211.
    1. Uchida H., Kamata M., Kato A., Mizukawa I., Watanabe A., Agematsu A., et al. One-year real-world clinical effectiveness, safety, and laboratory safety of dupilumab in Japanese adult patients with atopic dermatitis: a single-center retrospective study. J Am Acad Dermatol. 2021;84:547–550.
    1. Uchida H., Kamata M., Mizukawa I., Watanabe A., Agematsu A., Nagata M., et al. Real-world effectiveness and safety of dupilumab for the treatment of atopic dermatitis in Japanese patients: a single-centre retrospective study. Br J Dermatol. 2019;181:1083–1085.
    1. Uchida H., Kamata M., Nagata M., Fukaya S., Hayashi K., Fukuyasu A., et al. Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with higher baseline serum levels of immunoglobulin E and thymus and activation-regulated chemokine but not clinical severity in a real-world setting. J Am Acad Dermatol. 2020;82:1247–1249.
    1. Utine C.A., Li G., Asbell P., Pflugfelder S., Akpek E. Ocular surface disease associated with dupilumab treatment for atopic diseases. Ocul Surf. 2021;19:151–156.
    1. Vingopoulos F., Lazzaro D.R. Dupilumab-associated blepharoconjunctivitis with giant papillae. Int Med Case Rep J. 2020;13:303–305.
    1. Waldman R.A., DeWane M.E., Sloan B., Grant-Kels J.M. Characterizing dupilumab facial redness: a multi-institution retrospective medical record review. J Am Acad Dermatol. 2020;82:230–232.
    1. Wang C., Kraus C.N., Patel K.G., Ganesan A.K., Grando S.A. Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients' records. Int J Dermatol. 2020;59:253–256.
    1. 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 β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388:31–44.
    1. 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;368:2455–2466.
    1. Willsmore Z.N., Woolf R.T., Hughes C., Menon B., Kirkham B., Smith C.H., et al. Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series. Br J Dermatol. 2019;181:1068–1070.
    1. Wohlrab J., Werfel T., Wollenberg A. Pathomechanism of dupilumab-associated inflammatory eye symptoms. J Eur Acad Dermatol Venereol. 2019;33:e435–e436.
    1. Wollenberg A., Beck L.A., Blauvelt A., Simpson E.L., Chen Z., Chen Q., et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS) Br J Dermatol. 2020;182:1120–1135.
    1. Worm M., Simpson E.L., Thaçi D., Bissonnette R., Lacour J.P., Beissert S., et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156:131–143.
    1. Yamane M.L.M., Belsito D.V., Glass L.R.D. Two differing presentations of periocular dermatitis as a side effect of dupilumab for atopic dermatitis. Orbit. 2019;38:390–394.
    1. Yamauchi T., Sasaki S., Lee E.S., Tamura T., Seki M., Miwa T., et al. Dupilumab treatment ameliorates clinical and hematological symptoms, including blood eosinophilia, in patients with atopic dermatitis. Int J Dermatol. 2021;60:190–195.
    1. Yin L., Chen X., Vicini P., Rup B., Hickling T.P. Therapeutic outcomes, assessments, risk factors and mitigation efforts of immunogenicity of therapeutic protein products. Cell Immunol. 2015;295:118–126.
    1. Zhu G.A., Chen J.K., Chiou A., Ko J., Honari G. Assessment of the development of new regional dermatoses in patients treated for atopic dermatitis with dupilumab. JAMA Dermatol. 2019;155:850–852.

Source: PubMed

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