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Reviews on Recent Clinical Trials

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ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

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Review Article

Potential Indications of Dupilumab in Th-2 Inflammatory Disease

Author(s): Proietti Ilaria*, Skroza Nevena, Tolino Ersilia, Bernardini Nicoletta, Trovato Federica, Marco Di Fraia, Dybala Agniezska and Potenza Concetta

Volume 19, Issue 1, 2024

Published on: 20 December, 2023

Page: [53 - 61] Pages: 9

DOI: 10.2174/0115748871263396231121060901

Price: $65

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Abstract

Dupilumab is a fully humanized IgG4 monoclonal antibody, inhibiting IL-4 and IL-13 signaling, which are the main cytokines involved in type 2 inflammatory diseases. Its introduction was a breakthrough in the treatment of moderate-to-severe atopic dermatitis, but it is also used in other inflammatory diseases, including asthma, eosinophilic esophagitis and chronic rhinosinusitis with nasal polyposis. Recent advances in the understanding of inflammatory pathways have revealed that Th2-type inflammation is involved in a wider range of diseases than previously thought. The aim of our review is to examine off-label therapeutic indications of dupilumab, including bullous dermatoses (pemphigus, bullous pemphigoid) and alopecia areata, and to investigate its potential applications in cancer patients on anti-PD1 therapy.

Keywords: Dupilumab, inflammatory disease, alopecia areata, bullous disease, atopic dermatitis, th2.

« Previous Next »
[1]
Macdonald LE, Karow M, Stevens S, et al. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci USA 2014; 111(14): 5147-52.
[http://dx.doi.org/10.1073/pnas.1323896111] [PMID: 24706858]
[2]
Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol 2017; 13(5): 425-37.
[http://dx.doi.org/10.1080/1744666X.2017.1298443] [PMID: 28277826]
[3]
Kelly-Welch AE, Hanson EM, Boothby MR, Keegan AD. Interleukin-4 and interleukin-13 signaling connections maps. Science 2003; 300(5625): 1527-8.
[http://dx.doi.org/10.1126/science.1085458] [PMID: 12791978]
[4]
Keegan AD, Zamorano J, Keselman A, Heller NM. IL‐4 and IL‐13 re‐ ceptor signaling from 4PS to insulin receptor substrate 2: there and back again, a historical view. Front Immunol 2018; 9: 1037.
[http://dx.doi.org/10.3389/fimmu.2018.01037] [PMID: 29868002]
[5]
Chiaramonte MG, Mentink-Kane M, Jacobson BA, et al. Regulation and function of the interleukin 13 receptor α 2 during a T helper cell type 2-dominant immune response. J Exp Med 2003; 197(6): 687-701.
[http://dx.doi.org/10.1084/jem.20020903] [PMID: 12642601]
[6]
Sastre J, Dávila I. Dupilumab: A new paradigm for the treatment of allergic diseases. J Investig Allergol Clin Immunol 2018; 28(3): 139-50.
[http://dx.doi.org/10.18176/jiaci.0254] [PMID: 29939132]
[7]
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136(7): 2348-57.
[http://dx.doi.org/10.4049/jimmunol.136.7.2348] [PMID: 2419430]
[8]
Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 2007; 120(1): 150-5.
[http://dx.doi.org/10.1016/j.jaci.2007.04.031] [PMID: 17512043]
[9]
Kim J, Kim J, Cho D, Park H. Molecular mechanisms of cutaneous inflammatory disorder: Atopic dermatitis. Int J Mol Sci 2016; 17(8): 1234.
[http://dx.doi.org/10.3390/ijms17081234] [PMID: 27483258]
[10]
Tong P, Wesemann DR. Molecular mechanisms of IgE class switch recombination. Curr Top Microbiol Immunol 2015; 388: 21-37.
[http://dx.doi.org/10.1007/978-3-319-13725-4_2] [PMID: 25553793]
[11]
Iwaszko M, Biały S, Bogunia-Kubik K. Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis. Cells 2021; 10(11): 3000.
[http://dx.doi.org/10.3390/cells10113000] [PMID: 34831223]
[12]
Abuabara K, Hoffstad O, Troxel AB, Gelfand JM, McCulloch CE, Margolis DJ. Patterns and predictors of atopic dermatitis disease control past childhood: An observational cohort study. J Allergy Clin Immunol 2018; 141(2): 778-780.e6.
[http://dx.doi.org/10.1016/j.jaci.2017.05.031] [PMID: 28629748]
[13]
Sandilands A, Terron-Kwiatkowski A, Hull PR, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 2007; 39(5): 650-4.
[http://dx.doi.org/10.1038/ng2020] [PMID: 17417636]
[14]
Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 1974; 90(5): 525-30.
[http://dx.doi.org/10.1111/j.1365-2133.1974.tb06447.x] [PMID: 4601016]
[15]
Wilson SR, Thé L, Batia LM, et al. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 2013; 155(2): 285-95.
[http://dx.doi.org/10.1016/j.cell.2013.08.057] [PMID: 24094650]
[16]
González-López G, Ceballos-Rodríguez RM, González-López JJ, Feito Rodríguez M, Herranz-Pinto P. Efficacy and safety of wet wrap therapy for patients with atopic dermatitis: a systematic review and meta‐analysis. Br J Dermatol 2017; 177(3): 688-95.
[http://dx.doi.org/10.1111/bjd.15165] [PMID: 27861727]
[17]
Roekevisch E, Spuls PI, Kuester D, Limpens J, Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: A systematic review. J Allergy Clin Immunol 2014; 133(2): 429-38.
[http://dx.doi.org/10.1016/j.jaci.2013.07.049] [PMID: 24269258]
[18]
Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of atopic eczema (atopic dermatitis) Part I. J Eur Acad Dermatol Venereol 2012; 26(8): 1045-60.
[http://dx.doi.org/10.1111/j.1468-3083.2012.04635.x] [PMID: 22805051]
[19]
Thac i D, Simpson EL, Beck AL, 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(10013): 40-52.
[20]
Regeneron. Dupixent® (dupilumab) prescribing information. Important legal document for physicians prescribing dupilumab 2017.
[21]
Wollenberg A, Ariens L, Thurau S, van Luijk C, Seegräber M, de Bruin-Weller M. Conjunctivitis occurring in atopic dermatitis patients treated with dupilumab–clinical characteristics and treatment. J Allergy Clin Immunol Pract 2018; 6(5): 1778-1780.e1.
[http://dx.doi.org/10.1016/j.jaip.2018.01.034] [PMID: 29432961]
[22]
Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 2014; 371(2): 130-9.
[http://dx.doi.org/10.1056/NEJMoa1314768] [PMID: 25006719]
[23]
Vangipuram R, Tyring SK. Dupilumab for Moderate-to-Severe Atopic Dermatitis. Skin Therapy Lett 2017; 22(6): 1-4.
[PMID: 29091379]
[24]
Corren J. New targeted therapies for uncontrolled asthma. J Allergy Clin Immunol Pract. 2019;7(5):1394–403. Diamont Z, Dahlen S-E. Type 2 in ammation and the evolving profile of uncontrolled persistent asthma. Eur Med J 2018; 3(4): 24-33.
[25]
Tolino E, Proietti I, Sarni A, et al. Success of dupilumab as a monotherapy in an adult patient affected by severe uncontrolled asthma and atopic dermatitis. Dermatol Ther 2021; 34(1): e14596.
[http://dx.doi.org/10.1111/dth.14596] [PMID: 33244860]
[26]
Lucendo AJ, Molina-Infante J, Arias Á, et al. Guidelines on eosinophilic esophagitis: evidence‐based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J 2017; 5(3): 335-58.
[http://dx.doi.org/10.1177/2050640616689525] [PMID: 28507746]
[27]
Lucendo AJ, Arias-González L, Molina-Infante J, Arias Á. Systematic review: health-related quality of life in children and adults with eosinophilic oesophagitis-instruments for measurement and determinant factors. Aliment Pharmacol Ther 2017; 46(4): 401-9.
[http://dx.doi.org/10.1111/apt.14194] [PMID: 28639700]
[28]
Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: Improvement with an amino acid-based formula. Gastroenterology 1995; 109(5): 1503-12.
[http://dx.doi.org/10.1016/0016-5085(95)90637-1] [PMID: 7557132]
[29]
Molina-Infante J, Lucendo AJ. Dietary therapy for eosinophilic esophagitis. J Allergy Clin Immunol 2018; 142(1): 41-7.
[http://dx.doi.org/10.1016/j.jaci.2018.02.028] [PMID: 29522850]
[30]
Philpott H, Nandurkar S, Royce SG, Thien F, Gibson PR. Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities. Aliment Pharmacol Ther 2016; 44(3): 223-33.
[http://dx.doi.org/10.1111/apt.13676] [PMID: 27247257]
[31]
Lucendo AJ. Meta-Analysis-based guidance for dietary management in eosinophilic esophagitis. Curr Gastroenterol Rep 2015; 17(10): 37.
[http://dx.doi.org/10.1007/s11894-015-0464-y] [PMID: 26292666]
[32]
Arias Á, González-Cervera J, Tenias JM, Lucendo AJ. Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 2014; 146(7): 1639-48.
[http://dx.doi.org/10.1053/j.gastro.2014.02.006] [PMID: 24534634]
[33]
Rank MA, Sharaf RN, Furuta GT, et al. AGA institute. Technical review on the management of eosinophilic esophagitis: a report From the AGA institute and the joint task force on allergy-immunology practice parameters. Gastroenterology 2020; 158(6): 1789-1810.e15.
[http://dx.doi.org/10.1053/j.gastro.2020.02.039] [PMID: 32359563]
[34]
Matucci A, Vivarelli E, Nencini F, Maggi E, Vultaggio A. Strategies targeting Type 2 inflammation: from monoclonal antibodies to JAK-inhibitors. Biomedicines 2021; 9(10): 1497.
[http://dx.doi.org/10.3390/biomedicines9101497] [PMID: 34680614]
[35]
Hirano I, Dellon ES, Hamilton JD, et al. Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis. Gastroenterology 2020; 158(1): 111-122.e10.
[http://dx.doi.org/10.1053/j.gastro.2019.09.042] [PMID: 31593702]
[36]
Fokkens WJ, Lund VJ, Mullol J, et al. European position paper on rhinosinusitis and nasal polyps 2012 Rhinol Suppl 2012; 23(Suppl. 23): 3-1-298.
[PMID: 22764607]
[37]
Orlandi RR, Kingdom TT, Hwang PH. International consensus statement on allergy and rhinology: rhinosinusitis executive summary. Int Forum Allergy Rhinol 2016; 6(S1) (Suppl. 1): S3-S21.
[http://dx.doi.org/10.1002/alr.21694] [PMID: 26878819]
[38]
Veloso-Teles R, Cerejeira R. Endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps: Clinical outcome and predictive factors of recurrence. Am J Rhinol Allergy 2017; 31(1): 56-62.
[http://dx.doi.org/10.2500/ajra.2017.31.4402] [PMID: 28234156]
[39]
Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol 2017; 12(1): 331-57.
[http://dx.doi.org/10.1146/annurev-pathol-052016-100401] [PMID: 27959637]
[40]
Hulse KE. Immune mechanisms of chronic rhinosinusitis. Curr Allergy Asthma Rep 2016; 16(1): 1-8.
[http://dx.doi.org/10.1007/s11882-015-0579-0] [PMID: 26677109]
[41]
Desrosiers M, Mannent LP, Amin N, et al. Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP. Rhinology 2021; 0(0): 0.
[http://dx.doi.org/10.4193/Rhin20.415] [PMID: 33847325]
[42]
Laidlaw TM, Bachert C, Amin N, et al. Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol 2021; 126(5): 584-592.e1.
[http://dx.doi.org/10.1016/j.anai.2021.01.012] [PMID: 33465455]
[43]
Kwon CD, Khanna R, Williams KA, Kwatra MM, Kwatra SG. Diagnostic Workup and Evaluation of Patients with Prurigo Nodularis. Medicines (Basel) 2019; 6(4): 97.
[http://dx.doi.org/10.3390/medicines6040097] [PMID: 31561504]
[44]
Cao P, Xu W, Jiang S, Zhang L. Dupilumab for the treatment of prurigo nodularis: A systematic review. Front Immunol 2023; 14: 1092685.
[http://dx.doi.org/10.3389/fimmu.2023.1092685] [PMID: 36742321]
[45]
Kwatra SG. Breaking the itch-scratch cycle in prurigo nodularis. N Engl J Med 2020; 382(8): 757-8.
[http://dx.doi.org/10.1056/NEJMe1916733] [PMID: 32074425]
[46]
Husein-ElAhmed H, Steinhoff M. Dupilumab in prurigo nodularis: a systematic review of current evidence and analysis of predictive factors to response. J Dermatolog Treat 2022; 33(3): 1547-53.
[http://dx.doi.org/10.1080/09546634.2020.1853024] [PMID: 33200955]
[47]
Simpson EL, Akinlade B, Ardeleanu M. Two phase 3 trials of dupilumab versus. placebo in atopic dermatitis. N Engl J Med 2017; 376(11): 1090-1.
[http://dx.doi.org/10.1056/NEJMc1700366] [PMID: 28296614]
[48]
Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous pemphigoid. An Bras Dermatol 2019; 94(2): 133-46.
[http://dx.doi.org/10.1590/abd1806-4841.20199007]
[49]
Venning VA, Taghipour K, Mohd Mustapa MF, Highet AS, Kirtschig G. European dermatology forum. Guideline on the diagnosis and treatment of autoimmune bullous diseases - pemphigoid. In: British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012.
[50]
Russo R, Cozzani E, Gasparini G, Parodi A. Targeting interleukin 4 receptor α: A new approach to the treatment of cutaneous autoimmune bullous diseases? Dermatol Ther 2020; 33(1): e13190.
[http://dx.doi.org/10.1111/dth.13190] [PMID: 31863534]
[51]
Abdat R, Waldman RA, de Bedout V, et al. Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series. J Am Acad Dermatol 2020; 83(1): 46-52.
[http://dx.doi.org/10.1016/j.jaad.2020.01.089]
[52]
Bruni M, Moar A, Schena D, Girolomoni G. A case of nivolumab-induced bullous pemphigoid successfully treated with dupilumab. Dermatol Online J 2022; 28(2)
[http://dx.doi.org/10.5070/D328257396] [PMID: 35670683]
[53]
Zhang Y, Xu Q, Chen L, et al. Efficacy and safety of dupilumab in moderate-to-severe bullous pemphigoid. Front Immunol 2021; 12: 738907.
[http://dx.doi.org/10.3389/fimmu.2021.738907] [PMID: 34721404]
[54]
Cao P, Xu W, Zhang L. Rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid: A systematic review. Front Immunol 2022; 13: 928621.
[http://dx.doi.org/10.3389/fimmu.2022.928621] [PMID: 35769474]
[55]
Bishnoi A, De D, Handa S, Mahajan R. Biologics in autoimmune bullous diseases: Current scenario. Indian J Dermatol Venereol Leprol 2021; 87(5): 611-20.
[http://dx.doi.org/10.25259/IJDVL_886_19] [PMID: 34245525]
[56]
Tosti A, Bellavista S, Iorizzo M. Alopecia areata: A long term follow-up study of 191 patients. J Am Acad Dermatol 2006; 55(3): 438-41.
[http://dx.doi.org/10.1016/j.jaad.2006.05.008] [PMID: 16908349]
[57]
Phillips GS, et al. Treatment outcomes of immune-related cutaneous adverse events. J Clin Oncol 2019; 37(30): 2746-58.
[http://dx.doi.org/10.1200/JCO.18.02141]
[58]
Freitas E, Guttman-Yassky E, Torres T. Baricitinib for the treatment of alopecia areata. Drugs 2023; 83(9): 761-70.
[http://dx.doi.org/10.1007/s40265-023-01873-w] [PMID: 37195491]
[59]
King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med 2022; 386(18): 1687-99.
[http://dx.doi.org/10.1056/NEJMoa2110343] [PMID: 35334197]
[60]
Sibaud V. Dermatologic reactions to immune checkpoint inhibitors. Am J Clin Dermatol 2018; 19(3): 345-61.
[http://dx.doi.org/10.1007/s40257-017-0336-3] [PMID: 29256113]
[61]
Ribaud V, Boulinguez S, Pagès C, et al. Dermatologic toxicities of immune checkpoint inhibitors. Ann Dermatol Venereol 2018; 145(5): 313-30.
[http://dx.doi.org/10.1016/j.annder.2018.01.047]
[62]
Apalla Z, Rapoport B, Sibaud V. Dermatologic immune-related adverse events: The toxicity spectrum and recommendations for management. Int J Womens Dermatol 2021; 7(5) (5Part A): 625-35.
[http://dx.doi.org/10.1016/j.ijwd.2021.10.005] [PMID: 35005180]
[63]
Ramsey N, Berin MC. Pathogenesis of IgE‐mediated food allergy and implications for future immunotherapeutics. Pediatr Allergy Immunol 2021; 32(7): 1416-25.
[http://dx.doi.org/10.1111/pai.13501] [PMID: 33715245]
[64]
Burton OT, Medina Tamayo J, Stranks AJ, et al. IgE promotes type 2 innate lymphoid cells in murine food allergy. Clin Exp Allergy 2018; 48(3): 288-96.
[http://dx.doi.org/10.1111/cea.13075] [PMID: 29247574]
[65]
Study in pediatric subjects with peanut allergy to evaluate efficacy and safety of dupilumab as adjunct to AR101 (Peanut Oral Immunotherapy). NCT03682770, 2022.
[66]
Reinwald S, Rolland JM, O’Hehir RE, van Zelm MC. Peanut oral immunotherapy: Current trends in clinical trials. Immunotherapy Advances 2022; 2(1)(ltac004.)
[http://dx.doi.org/10.1093/immadv/ltac004] [PMID: 35919493]
[67]
Gaig P, Olona M, Muñoz Lejarazu D, et al. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol 2004; 14(3): 214-20.
[PMID: 15552715]
[68]
Kolkhir P, Church MK, Weller K, Metz M, Schmetzer O, Maurer M. Autoimmune chronic spontaneous urticaria: What we know and what we do not know. J Allergy Clin Immunol 2017; 139(6): 1772-1781.e1.
[http://dx.doi.org/10.1016/j.jaci.2016.08.050] [PMID: 27777182]
[69]
Zuberbier T, Abdul Latiff AH, Abuzakouk M, Abuzakouk M, Aquilina S, Asero R, et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy 2022; 77(3): 734-66.
[70]
Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014; 1CD003559.
[http://dx.doi.org/10.1002/14651858.CD003559.pub4]
[71]
Lee JK, Simpson RS. Dupilumab as a novel therapy for difficult to treat chronic spontaneous urticaria. J Allergy Clin Immunol Pract 2019; 7(5): 1659-1661.e1.
[http://dx.doi.org/10.1016/j.jaip.2018.11.018] [PMID: 30496828]

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