Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience
Background. Dupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effect...
- Autores:
-
Londoño, Julián
Pérez, Lucia
Moreno, Sergio
Chapman, Edgardo
Beatriz García, María
Celis, Ana María
Muñoz, María Angélica
Castillo, David
Sánchez, Jorge
Arevalo, Yaicith
Lozano, Ana
Muñoz, Cesar
Botero, Laura
Beltran, Catalina
García, Elizabeth
Alvis Zakzuk, Nelson Rafael
Alvis Zakzuk, Nelson J.
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2023
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/10454
- Acceso en línea:
- https://hdl.handle.net/11323/10454
https://repositorio.cuc.edu.co/
- Palabra clave:
- Atopic dermatitis
Dupilumab
Eczema
Biologic therapy
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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dc.title.eng.fl_str_mv |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
title |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
spellingShingle |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience Atopic dermatitis Dupilumab Eczema Biologic therapy |
title_short |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
title_full |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
title_fullStr |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
title_full_unstemmed |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
title_sort |
Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experience |
dc.creator.fl_str_mv |
Londoño, Julián Pérez, Lucia Moreno, Sergio Chapman, Edgardo Beatriz García, María Celis, Ana María Muñoz, María Angélica Castillo, David Sánchez, Jorge Arevalo, Yaicith Lozano, Ana Muñoz, Cesar Botero, Laura Beltran, Catalina García, Elizabeth Alvis Zakzuk, Nelson Rafael Alvis Zakzuk, Nelson J. |
dc.contributor.author.none.fl_str_mv |
Londoño, Julián Pérez, Lucia Moreno, Sergio Chapman, Edgardo Beatriz García, María Celis, Ana María Muñoz, María Angélica Castillo, David Sánchez, Jorge Arevalo, Yaicith Lozano, Ana Muñoz, Cesar Botero, Laura Beltran, Catalina García, Elizabeth Alvis Zakzuk, Nelson Rafael Alvis Zakzuk, Nelson J. |
dc.subject.proposal.eng.fl_str_mv |
Atopic dermatitis Dupilumab Eczema Biologic therapy |
topic |
Atopic dermatitis Dupilumab Eczema Biologic therapy |
description |
Background. Dupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effectiveness and safety of dupilumab in adults with moderate to severe AD in a Colombian multicenter cohort. Methods.Multicenter descriptive study that included patients who started treatment between March 2018 and May 2020 in 6 centers. Disease severity was assessed using the following: Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). These measurements were collected according to availability at baseline, 3–5 months, 6–12 months, and more than 12 months. Days of sick leave, hospitalizations, and AD flares before and after dupilumab treatment were reported. Adverse events (AEs) were recorded during follow-up. Results. Ninety-three patients were included, with a median age of 32 years (IQR: 24.0; 40.0) and a disease evolution time of 21 years (IQR: 16.0; 29.5). 88.2% had at least 1 allergic disease other than AD. An improvement greater than or equal to 75% EASI was observed in 41.7% of patients at 3–5 months, in 73.7% of patients at 6–12 months, and in 75.0% of patients after 12 months. For those reporting SCORAD and POEM, the median percent change ([IQR], n) from baseline in SCORAD was −67.1 ([−79.2; −54.2], n = 16), −70.5 ([−85.8; −47.9], n = 36) and −66.7 ([−77.3; −51.0], n = 13); and POEM, −58.6 ([−66.4; −55.5], n = 4), −73.0 ([−86.5; −66.7], n = 16) and −87.3 ([−93.4; −69.6], n = 8), respectively. Before initiation of dupilumab treatment, 82 (88.2%) patients reported at least 1 flare of AD in the past 12 months. During the follow-up period, 30 (32.3%) patients reported at least 1 exacerbation or flare. Twelve patients (12.9%) presented an AE and 3 (3.2%) patients discontinued dupilumab for this cause. Conclusions. Dupilumab was effective and safe for the treatment of moderate to severe AD in point-of-care settings, with results similar to randomized controlled and other real-life studies. These positive results are still maintained even though a high number of patients had short interruptions in the use of dupilumab due to administrative problems. |
publishDate |
2023 |
dc.date.accessioned.none.fl_str_mv |
2023-09-07T16:33:03Z |
dc.date.available.none.fl_str_mv |
2023-09-07T16:33:03Z |
dc.date.issued.none.fl_str_mv |
2023 |
dc.type.spa.fl_str_mv |
Artículo de revista |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ART |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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dc.identifier.citation.spa.fl_str_mv |
Julián Londoño, Lucia Perez, Sergio Moreno, Edgardo Chapman, María Beatriz Garcia, Ana María Celis, María Angélica Muñoz, David Castillo, Jorge Sánchez, Yaicith Arevalo, Ana Lozano, Nelson J. Alvis-Zakzuk, Cesar Muñoz, Laura Botero, Catalina Beltran, Elizabeth García, Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: Real-life experience, World Allergy Organization Journal, Volume 16, Issue 4, 2023, 100763, ISSN 1939-4551, https://doi.org/10.1016/j.waojou.2023.100763 |
dc.identifier.issn.spa.fl_str_mv |
1939-4551 |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/11323/10454 |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.waojou.2023.100763 |
dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
identifier_str_mv |
Julián Londoño, Lucia Perez, Sergio Moreno, Edgardo Chapman, María Beatriz Garcia, Ana María Celis, María Angélica Muñoz, David Castillo, Jorge Sánchez, Yaicith Arevalo, Ana Lozano, Nelson J. Alvis-Zakzuk, Cesar Muñoz, Laura Botero, Catalina Beltran, Elizabeth García, Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: Real-life experience, World Allergy Organization Journal, Volume 16, Issue 4, 2023, 100763, ISSN 1939-4551, https://doi.org/10.1016/j.waojou.2023.100763 1939-4551 10.1016/j.waojou.2023.100763 Corporación Universidad de la Costa REDICUC - Repositorio CUC |
url |
https://hdl.handle.net/11323/10454 https://repositorio.cuc.edu.co/ |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofjournal.spa.fl_str_mv |
World Allergy Organization Journal |
dc.relation.references.spa.fl_str_mv |
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The burden of atopic dermatitis: summary of a report for the national eczema association. J Investig Dermatol. 2017;137:26–30. Elsevier B.V. 6. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study [cited 2021 Aug 20] Ann Allergy Asthma Immunol [Internet]. 2018 Sep 1;121(3): 340–347. Available from: https://pubmed.ncbi.nlm.nih.gov/ 30025911/. 7. Murray CJL, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990– 2010: a systematic analysis for the Global Burden of Disease Study 2010 [cited 2021 Aug 20] Lancet [Internet]. 2012 Dec 15;380(9859):2197–2223. Available from: http://www. thelancet.com/article/S0140673612616894/fulltext. 8. 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):130–139. 9. Simpson EL, Bieber T, Guttman-Yassky E, et al. 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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) [cited 2020 Dec 17] Br J Dermatol [Internet]. 2018 May 1;178(5):1083–1101. Available from: https://pubmed.ncbi.nlm.nih.gov/29193016/. 17. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis [cited 2020 Dec 17] N Engl J Med [Internet]. 2016 Dec 15;375(24): 2335–2348. Available from: https://www.nejm.org/doi/10. 1056/NEJMoa1610020. 18. Caraballo L, Zakzuk J, Lee BW, et al. Particularities of allergy in the tropics [cited 2021 Aug 12] World Allergy Organ J [Internet]. 2016;9:20. Available from: http://www.ncbi.nlm.nih. gov/pubmed/27386040. 19. Pérez-Herrera LC, Moreno-López S, Peñaranda D, García E, Chapman E, Peñaranda A. Frequency of self-reported allergies at a high-complexity referral hospital in Colombia, a tropical Latin American country [cited 2022 Jun 9] Allergol Immunopathol (Madr) [Internet]. 2021 Sep 1;49(5):100–105. Available from: https://www.all-imm.com/index.php/aei/ article/view/449/627. 20. Nettis E, Patella V, Lombardo C, et al. Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis [cited 2021 Nov 16] Allergy [Internet]. 2020 Oct 1;75(10):2653–2661. Available from: https://pubmed.ncbi. nlm.nih.gov/32424957/. 21. Ribero S, Giura MT, Viola R, et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in adult cohort: a real-life Italian tertiary centre experience [cited 2021 Nov 16] J Eur Acad Dermatol Venereol [Internet]. 2020 Aug 1;34(8):e380–e383. Available from: https://pubmed.ncbi.nlm. nih.gov/31960496/. 22. Quint T, Brunner PM, Sinz C, et al. Dupilumab for the treatment of atopic dermatitis in an Austrian cohort-real-life data shows Rosacea-like Folliculitis [cited 2021 Nov 16] J Clin Med [Internet]. 2020 Apr 1;9(4). Available from: https://pubmed. ncbi.nlm.nih.gov/32344789/. 23. Armario-Hita JC, Pereyra-Rodriguez J, Silvestre JF, et al. Treatment of moderate-to-severe atopic dermatitis with dupilumab in real clinical practice: a multicentre, retrospective case series [cited 2021 Nov 16] Br J Dermatol [Internet]. 2019 Nov 1;181(5):1072–1074. Available from: https://pubmed. ncbi.nlm.nih.gov/31021399/. 24. Ruiz-Villaverde R, Dominguez-Cruz J, Armario-Hita JC, et al. Fifty-two week follow-up safety and effectiveness results of dupilumab treatment of moderate-to-severe atopic dermatitis from a retrospective, multicentric series [cited 2021 Nov 16]. Dermatol Ther [Internet]. 2019;32(4):e12931. Available from: https://pubmed.ncbi.nlm.nih.gov/30980485/. 25. John Wiley & Sons, Ltd Armario-Hita JC, Pereyra-Rodriguez J, Silvestre JF, et al. Treatment of moderate-to-severe atopic dermatitis with dupilumab in real clinical practice: a multicentre, retrospective case series [Internet] [cited 2021 Sep 18] Br J Dermatol. 2019;vol. 181:1072–1074. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/bjd. 18041. 26. Abraham S, Haufe E, Harder I, et al. Implementation of dupilumab in routine care of atopic eczema: results from the German national registry TREATgermany [Internet] [cited 2021 Sep 18] British Journal of Dermatology. Br J Dermatol. 2020;183:382–384. Available from: https://pubmed.ncbi.nlm. nih.gov/32068242/. 27. Kreeshan FC, Al-Janabi A, Warren RB, Hunter HJA. Real-World experience and laboratory monitoring of dupilumab in patients with moderate to severe atopic dermatitis in a tertiary centre [cited 2021 Nov 16] Dermatol Ther (Heidelb) [Internet]. 2021 Feb 1;11(1):149–160. Available from: https://pubmed. ncbi.nlm.nih.gov/33315229/. 28. Fargnoli MC, Esposito M, Ferrucci S, et al. A 48-week update of a multicentre real-life experience of dupilumab in adult patients with moderate-to-severe atopic dermatitis. J Dermatolog Treat [Internet]. 2022 Mar;33(2):1146–1149 [cited 2021 Nov 16]; Available from: https://pubmed.ncbi.nlm.nih. gov/32436765/ [cited 2021 Nov 16]; Available from:. 29. Sanchez J, Cherrez-Ojeda I, Galvan C, et al. The unmet needs in atopic dermatitis control in Latin America: a multidisciplinary expert perspective [cited 2021 Sep 18] Dermatology Ther 2021 [Internet]; 2021 Aug 27:1–20. Available from: https://link. springer.com/article/10.1007/s13555-021-00595-9. 30. Akinlade B, Guttman-Yassky E, de Bruin-Weller M, et al. Conjunctivitis in dupilumab clinical trials [cited 2021 Nov 16] Br J Dermatol [Internet]. 2019 Sep 1;181(3):459–473. Available from: https://pubmed.ncbi.nlm.nih.gov/30851191/. 31. 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 [cited 2021 Nov 16] J allergy Clin Immunol Pract [Internet]. 2018 Sep 1;6(5):1778–1780.e1. Available from: https://pubmed.ncbi.nlm.nih.gov/29432961/. 32. Ivert LU, Wahlgren CF, Ivert L, Lundqvist M, Bradley M. Eye complications during dupilumab treatment for severe atopic dermatitis [cited 2021 Nov 16] Acta Derm Venereol [Internet]. 2019 Apr 1;99(4):375–378. Available from: https://pubmed. ncbi.nlm.nih.gov/30653240/. 33. de Wijs LEM, Nguyen NT, Kunkeler ACM, Nijsten T, Damman J, Hijnen DJ. Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series [cited 2021 Nov 16] Br J Dermatol [Internet]. 2020 Oct 1;183(4):745–749. Available from: https://pubmed.ncbi.nlm.nih.gov/31749159/. 34. Barnes AC, Blandford AD, Perry JD. Cicatricial ectropion in a patient treated with dupilumab [cited 2021 Nov 16] Am J Ophthalmol case reports [Internet]. 2017 Sep 1;7:120–122. Available from: https://pubmed.ncbi.nlm.nih.gov/29260094/. 35. Maudinet A, Law-Koune S, Duretz C, Lasek A, Modiano P, Tran THC. Ocular surface diseases Induced by dupilumab in severe atopic dermatitis [cited 2021 Nov 16] Ophthalmol Ther [Internet]. 2019 Sep 1;8(3):485–490. Available from: https:// pubmed.ncbi.nlm.nih.gov/31230264/. 36. Halling AS, Loft N, Silverberg JI, Guttman-Yassky E, Thyssen JP. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis [cited 2021 Nov 16] J Am Acad Dermatol [Internet]. 2021 Jan 1;84(1):139–147. Available from: https://pubmed.ncbi.nlm.nih.gov/32822798/. 37. Ferrucci S, Angileri L, Tavecchio S, et al. Elevation of peripheral blood eosinophils during dupilumab treatment for atopic dermatitis is associated with baseline comorbidities and development of facial redness dermatitis and ocular surface disease. J Dermatol Treat. 2022 Aug;33(5):2587–2592. 38. Máspero J, Angles MV, Ardusso L, et al. Análisis de una serie de casos de pacientes adultos con dermatitis atópica severa tratados con dupilumab en Argentina [cited 2023 Jan 14] Rev Fac Cien Med Univ Nac Cordoba [Internet]. 2020 Jun 9;77(2): 94–99. Available from: https://pubmed.ncbi.nlm.nih.gov/ 32558511/. 39. Vergara C, Caraballo L, Mercado D, et al. African ancestry is associated with risk of asthma and high total serum IgE in a population from the Caribbean Coast of Colombia [cited 2022 May 2] Hum Genet [Internet]. 2009;125(5–6):565–579. Available from: https://pubmed.ncbi.nlm.nih.gov/19290544/. 40. Touhouche AT, Cassagne M, Bérard E, et al. Incidence and risk factors for dupilumab associated ocular adverse events: a reallife prospective study. J Eur Acad Dermatol Venereol. 2021 Jan;35(1):172–179. |
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© 2023 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organization |
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Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) © 2023 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organization https://creativecommons.org/licenses/by-nc-nd/4.0/ http://purl.org/coar/access_right/c_abf2 |
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Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)© 2023 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organizationhttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Londoño, JuliánPérez, LuciaMoreno, SergioChapman, EdgardoBeatriz García, MaríaCelis, Ana MaríaMuñoz, María AngélicaCastillo, DavidSánchez, JorgeArevalo, YaicithLozano, AnaMuñoz, CesarBotero, LauraBeltran, CatalinaGarcía, ElizabethAlvis Zakzuk, Nelson RafaelAlvis Zakzuk, Nelson J.virtual::263-12023-09-07T16:33:03Z2023-09-07T16:33:03Z2023Julián Londoño, Lucia Perez, Sergio Moreno, Edgardo Chapman, María Beatriz Garcia, Ana María Celis, María Angélica Muñoz, David Castillo, Jorge Sánchez, Yaicith Arevalo, Ana Lozano, Nelson J. Alvis-Zakzuk, Cesar Muñoz, Laura Botero, Catalina Beltran, Elizabeth García, Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: Real-life experience, World Allergy Organization Journal, Volume 16, Issue 4, 2023, 100763, ISSN 1939-4551, https://doi.org/10.1016/j.waojou.2023.1007631939-4551https://hdl.handle.net/11323/1045410.1016/j.waojou.2023.100763Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/Background. Dupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effectiveness and safety of dupilumab in adults with moderate to severe AD in a Colombian multicenter cohort. Methods.Multicenter descriptive study that included patients who started treatment between March 2018 and May 2020 in 6 centers. Disease severity was assessed using the following: Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). These measurements were collected according to availability at baseline, 3–5 months, 6–12 months, and more than 12 months. Days of sick leave, hospitalizations, and AD flares before and after dupilumab treatment were reported. Adverse events (AEs) were recorded during follow-up. Results. Ninety-three patients were included, with a median age of 32 years (IQR: 24.0; 40.0) and a disease evolution time of 21 years (IQR: 16.0; 29.5). 88.2% had at least 1 allergic disease other than AD. An improvement greater than or equal to 75% EASI was observed in 41.7% of patients at 3–5 months, in 73.7% of patients at 6–12 months, and in 75.0% of patients after 12 months. For those reporting SCORAD and POEM, the median percent change ([IQR], n) from baseline in SCORAD was −67.1 ([−79.2; −54.2], n = 16), −70.5 ([−85.8; −47.9], n = 36) and −66.7 ([−77.3; −51.0], n = 13); and POEM, −58.6 ([−66.4; −55.5], n = 4), −73.0 ([−86.5; −66.7], n = 16) and −87.3 ([−93.4; −69.6], n = 8), respectively. Before initiation of dupilumab treatment, 82 (88.2%) patients reported at least 1 flare of AD in the past 12 months. During the follow-up period, 30 (32.3%) patients reported at least 1 exacerbation or flare. Twelve patients (12.9%) presented an AE and 3 (3.2%) patients discontinued dupilumab for this cause. Conclusions. Dupilumab was effective and safe for the treatment of moderate to severe AD in point-of-care settings, with results similar to randomized controlled and other real-life studies. These positive results are still maintained even though a high number of patients had short interruptions in the use of dupilumab due to administrative problems.12 páginasapplication/pdfengBioMed Central Ltd.United Kingdomhttps://www.sciencedirect.com/science/article/pii/S1939455123000236Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: real-life experienceArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85ColombiaWorld Allergy Organization Journal1. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis [Internet]. Nature Reviews Disease Primers. Nat Rev Dis Primers. 2018;4 [cited 2021 Aug 20]. Available from: https://pubmed.ncbi.nlm.nih.gov/29930242/.2. Dennis RJ, Caraballo L, García E, et al. 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J Eur Acad Dermatol Venereol. 2021 Jan;35(1):172–179.121416Atopic dermatitisDupilumabEczemaBiologic therapyPublicationf8e59b41-ba4f-49d6-bd45-40986ed6da71969b7cc2-4eeb-48c0-b0b4-eb93f794dd65virtual::263-1969b7cc2-4eeb-48c0-b0b4-eb93f794dd65virtual::263-1https://scholar.google.com/citations?user=HcYVxUwAAAAJ&hl=enhttps://scholar.google.com.co/citations?user=Paic_C8AAAAJ&hl=esvirtual::263-10000-0001-9136-97750000-0001-9382-214Xvirtual::263-1ORIGINALEffectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia.pdfEffectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia.pdfArtículosapplication/pdf712702https://repositorio.cuc.edu.co/bitstreams/06456283-a4fa-4198-bf82-6a94cde92828/downloadea5a45ae5952db2b3ceed7416bb545acMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.cuc.edu.co/bitstreams/b1be55e5-31d8-4224-bc67-9d3edba3f391/download2f9959eaf5b71fae44bbf9ec84150c7aMD52TEXTEffectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia.pdf.txtEffectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia.pdf.txtExtracted texttext/plain43203https://repositorio.cuc.edu.co/bitstreams/e71eb378-27f1-4011-8525-7605d2b77173/downloadb1d332f997510110145c71795aaece7eMD53THUMBNAILEffectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia.pdf.jpgEffectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia.pdf.jpgGenerated Thumbnailimage/jpeg17042https://repositorio.cuc.edu.co/bitstreams/2d6a6735-d8e2-4b54-a892-8d8f0458ee13/downloadcdf9dc162120b5886e4fb218d870e123MD5411323/10454oai:repositorio.cuc.edu.co:11323/104542025-02-25 12:30:48.204https://creativecommons.org/licenses/by-nc-nd/4.0/© 2023 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organizationopen.accesshttps://repositorio.cuc.edu.coRepositorio de la Universidad de la Costa 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ada en las Obras Colectivas.

b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda.

c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas. Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).

4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:

a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).

b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.

c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.

d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:

i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.

ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.

e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.

5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

7. Término.

a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.

b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.

8. Varios.

a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.

b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.

c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.

d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.
 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