nach oben

European Archives of Oto-Rhino-Laryngology

19.05.2024 | Review Article

Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature

verfasst von: Marella Reale, Giuseppe Licci, Pietro Orlando, Andrea Matucci, Franco Trabalzini, Giandomenico Maggiore, Oreste Gallo

Erschienen in: European Archives of Oto-Rhino-Laryngology

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking.

Materials and methods

A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment.

Results

15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic.

Conclusion

Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.

Kato A, Peters AT, Stevens WW et al (2022) Endotypes of chronic rhinosinusitis: relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches. Allergy 77(3):812–826. https://doi.org/10.1111/all.15074CrossRefPubMed

Han X, Wu D, Sun Z et al (2020) Type 1/type 2 inflammatory cytokines correlate with olfactory function in patients with chronic rhinosinusitis. Am J Otolaryngol 41(5):102587. https://doi.org/10.1016/j.amjoto.2020.102587CrossRefPubMed

Mattos JL, Schlosser RJ, Storck KA, Soler ZM (2017) Understanding the relationship between olfactory-specific quality of life, objective olfactory loss, and patient factors in chronic rhinosinusitis. Int Forum Allergy Rhinol 7(7):734–740. https://doi.org/10.1002/alr.21940CrossRefPubMedPubMedCentral

Frasnelli J, Hummel T (2005) Olfactory dysfunction and daily life. Eur Arch Otorhinolaryngol 262(3):231–235. https://doi.org/10.1007/s00405-004-0796-yCrossRefPubMed

Mattos JL, Schlosser RJ, DeConde AS et al (2018) Factor analysis of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol 8(7):777–782. https://doi.org/10.1002/alr.22112CrossRefPubMedPubMedCentral

Samitas K, Carter A, Kariyawasam HH, Xanthou G (2018) Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: the one airway concept revisited. Allergy 73(5):993–1002. https://doi.org/10.1111/all.13373CrossRefPubMed

Håkansson K, Thomsen SF, Konge L et al (2014) A comparative and descriptive study of asthma in chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy 28(5):383–387. https://doi.org/10.2500/ajra.2014.28.4076CrossRefPubMed

Hoffmans R, Wagemakers A, van Drunen C et al (2018) Acute and chronic rhinosinusitis and allergic rhinitis in relation to comorbidity, ethnicity and environment. PLoS One 13(2):e0192330. https://doi.org/10.1371/journal.pone.0192330CrossRefPubMedPubMedCentral

Stevens WW, Peters AT, Hirsch AG et al (2017) Clinical characteristics of patients with chronic rhinosinusitis with nasal polyps, asthma, and aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract 5(4):1061-1070.e3. https://doi.org/10.1016/j.jaip.2016.12.027CrossRefPubMedPubMedCentral

10.

Alsharif S, Jonstam K, van Zele T et al (2019) Endoscopic sinus surgery for type-2 CRS wNP: an endotype-based retrospective study. Laryngoscope 129(6):1286–1292. https://doi.org/10.1002/lary.27815CrossRefPubMed

11.

Wechsler ME (2013) Inhibiting interleukin-4 and interleukin-13 in difficult-to-control asthma. N Engl J Med 368(26):2511–2513. https://doi.org/10.1056/NEJMe1305426CrossRefPubMed

12.

Bachert C, Han JK, Desrosiers M et al (2019) Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 394(10209):1638–1650. https://doi.org/10.1016/S0140-6736(19)31881-1CrossRefPubMed

13.

De Corso E, Settimi S, Montuori C et al (2022) Effectiveness of Dupilumab in the treatment of patients with severe uncontrolled CRSwNP: a “real-life” observational study in the first year of treatment. J Clin Med 11(10):2684. https://doi.org/10.3390/jcm11102684CrossRefPubMedPubMedCentral

14.

Ottaviano G, Saccardo T, Roccuzzo G et al (2022) Effectiveness of Dupilumab in the treatment of patients with uncontrolled severe CRSwNP: a “real-life” observational study in naïve and post-surgical patients. J Pers Med 12(9):1526. https://doi.org/10.3390/jpm12091526CrossRefPubMedPubMedCentral

15.

van der Lans RJL, Fokkens WJ, Adriaensen GFJPM et al (2022) Real-life observational cohort verifies high efficacy of dupilumab for chronic rhinosinusitis with nasal polyps. Allergy. 77(2):670–674. https://doi.org/10.1111/all.15134CrossRefPubMed

16.

Nettis E, Brussino L, Patella V et al (2022) Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life. Clin Mol Allergy 20(1):6. https://doi.org/10.1186/s12948-022-00171-2CrossRefPubMedPubMedCentral

17.

Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700CrossRefPubMedPubMedCentral

18.

Meltzer EO, Hamilos DL, Hadley JA et al (2006) Rhinosinusitis: developing guidance for clinical trials. J Allergy Clin Immunol 118(5 Suppl):S17–S61. https://doi.org/10.1016/j.jaci.2006.09.005CrossRefPubMed

19.

Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP (2009) Psychometric validity of the 22-item sinonasal outcome test. Clin Otolaryngol 34(5):447–454. https://doi.org/10.1111/j.1749-4486.2009.01995.xCrossRefPubMed

20.

Lund VJ, Mackay IS (1993) Staging in rhinosinusitus. Rhinology 31(4):183–184PubMed

21.

Kilty SJ, Lasso A (2022) Canadian real-world study of access and clinical results using dupilumab for chronic rhinosinusitis with polyps. J Otolaryngol Head Neck Surg 51(1):17. https://doi.org/10.1186/s40463-022-00570-0CrossRefPubMedPubMedCentral

22.

Grose E, Li AY, Lee JM (2023) Clinical outcomes of dupilumab therapy in chronic rhinosinusitis with nasal polyps in a Canadian tertiary care rhinology practice. Allergy Asthma Clin Immunol 19(1):26. https://doi.org/10.1186/s13223-023-00782-7CrossRefPubMedPubMedCentral

23.

Jansen F, Becker B, Eden JK et al (2023) Dupilumab (Dupixent^®) tends to be an effective therapy for uncontrolled severe chronic rhinosinusitis with nasal polyps: real data of a single-centered, retrospective single-arm longitudinal study from a university hospital in Germany. Eur Arch Otorhinolaryngol 280(4):1741–1755. https://doi.org/10.1007/s00405-022-07679-yCrossRefPubMed

24.

Boscke R, Heidemann M, Bruchhage KL (2023) Dupilumab for chronic rhinosinusitis with nasal polyps: real-life retrospective 12-month effectiveness data. Rhinology 61(3):203–213. https://doi.org/10.4193/Rhin22.469CrossRefPubMed

25.

De Corso E, Pasquini E, Trimarchi M et al (2023) Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): a multicentric observational phase IV real-life study (DUPIREAL). Allergy 78(10):2669–2683. https://doi.org/10.1111/all.15772CrossRefPubMed

26.

Galletti C, Barbieri MA, Ciodaro F et al (2023) Effectiveness and safety profile of Dupilumab in chronic rhinosinusitis with nasal polyps: real-life data in tertiary care. Pharmaceuticals 16(4):630. https://doi.org/10.3390/ph16040630CrossRefPubMedPubMedCentral

27.

Albrecht T, Sailer MM, Capitani F et al (2023) Real-world evidence for the effectiveness and safety of dupilumab in patients with CRSwNP after 1 year of therapy. World Allergy Organ J 16(5):100780. https://doi.org/10.1016/j.waojou.2023.100780CrossRefPubMedPubMedCentral

28.

van der Lans RJL, Otten JJ, Adriaensen GFJPM et al (2023) Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months. Allergy 78(10):2684–2697. https://doi.org/10.1111/all.15796CrossRefPubMed

29.

Pecorari G, Piazza F, Borgione M et al (2023) The role of intranasal corticosteroids in chronic rhinosinusitis with nasal polyposis treated with dupilumab. Am J Otolaryngol 44(5):103927. https://doi.org/10.1016/j.amjoto.2023.103927CrossRefPubMed

30.

Bertlich M, Freytag S, Dombrowski T et al (2022) Subgroups in the treatment of nasal polyposis with dupilumab: a retrospective study. Medicine 101(45):e31031. https://doi.org/10.1097/MD.0000000000031031CrossRefPubMedPubMedCentral

31.

Campion NJ, Brugger J, Tu A et al (2023) The “real life” efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP. J Otolaryngol Head Neck Surg 52(1):56. https://doi.org/10.1186/s40463-023-00663-4CrossRefPubMedPubMedCentral

32.

Giombi F, Pace GM, Nappi E et al (2023) Radiological versus clinical 1-year outcomes of Dupilumab in refractory CRSwNP: a real-life study. Laryngoscope. https://doi.org/10.1002/lary.31238CrossRefPubMed

33.

Orlando P, Licci G, Kuitche D et al (2023) Effectiveness of dupilumab versus endoscopic sinus surgery for the treatment of type-2 chronic rhinosinusitis with nasal polyps: a preliminary report. Eur Arch Otorhinolaryngol. https://doi.org/10.1007/s00405-023-08309-xCrossRefPubMed

34.

Bellocchi G, Loperfido A, Passali FM et al (2023) Biologics in severe uncontrolled chronic rhinosinusitis with nasal polyps: a bicentric experience. Acta Biomed 94(5):e2023227. https://doi.org/10.23750/abm.v94i5.14745CrossRefPubMedPubMedCentral

35.

Schmale IL, Poulakis A, Abend A, Luitje ME, Man LX (2023) Chronic rhinosinusitis with nasal polyposis treated with Dupilumab: real-world use and outcomes. J Allergy Clin Immunol Pract 11(10):3203–3210. https://doi.org/10.1016/j.jaip.2023.07.038CrossRefPubMed

36.

Mocellin D, Ioppi A, Gaglio G et al (2023) Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness. Eur Rev Med Pharmacol Sci 27(15):7324–7336. https://doi.org/10.26355/eurrev_202308_33304CrossRefPubMed

37.

Laidlaw TM, Bachert C, Amin N et al (2021) Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol 126(5):584-592.e1. https://doi.org/10.1016/j.anai.2021.01.012CrossRefPubMed

38.

Fokkens WJ, Lund VJ, Hopkins C et al (2020) European position paper on rhinosinusitis and nasal polyps 2020. Rhinol 58(Suppl S29):1–464. https://doi.org/10.4193/Rhin20.600CrossRef

39.

Rollema C, van Roon EN, Ekhart C et al (2022) Adverse drug reactions of intranasal corticosteroids in the Netherlands: an analysis from the Netherlands pharmacovigilance center. Drugs Real World Outcomes 9(3):321–331. https://doi.org/10.1007/s40801-022-00301-xCrossRefPubMedPubMedCentral

40.

Minagawa S, Araya J, Watanabe N et al (2022) Real-life effectiveness of dupilumab in patients with mild to moderate bronchial asthma comorbid with CRSwNP. BMC Pulm Med 22(1):258. https://doi.org/10.1186/s12890-022-02046-3CrossRefPubMedPubMedCentral

41.

Hopkins C, Wagenmann M, Bachert C et al (2021) Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol 11(7):1087–1101. https://doi.org/10.1002/alr.22780CrossRefPubMedPubMedCentral

42.

Alicandri-Ciufelli M, Marchioni D, Pipolo C et al (2023) Influence of prior endoscopic sinus surgery extent on dupilumab effectiveness in CRSwNP patients. Laryngoscope. https://doi.org/10.1002/lary.30983CrossRefPubMed

43.

Krings JG, Kallogjeri D, Wineland A et al (2014) Complications of primary and revision functional endoscopic sinus surgery for chronic rhinosinusitis. Laryngoscope 124(4):838–845. https://doi.org/10.1002/lary.24401CrossRefPubMed

44.

Bhattacharyya N (2004) Clinical outcomes after revision endoscopic sinus surgery. Arch Otolaryngol Head Neck Surg 130(8):975–978. https://doi.org/10.1001/archotol.130.8.975CrossRefPubMed

45.

Fokkens WJ, Viskens AS, Backer V et al (2023) EPOS/EUFOREA update on indication and evaluation of biologics in chronic rhinosinusitis with nasal polyps 2023. Rhinology 61(3):194–202. https://doi.org/10.4193/Rhin22.489CrossRefPubMed

46.

Caminati M, Olivieri B, Dama A et al (2022) Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. Expert Rev Respir Med 16(7):713–721. https://doi.org/10.1080/17476348.2022.2090342CrossRefPubMed

47.

Vinciguerra A, Rampi A, Yacoub MR et al (2022) Hypereosinophilia management in patients with type 2 chronic rhinosinusitis treated with dupilumab: preliminary results. Eur Arch Otorhinolaryngol 279(11):5231–5238. https://doi.org/10.1007/s00405-022-07389-5CrossRefPubMed

48.

Darkhal P, Gao M, Ma Y, Liu D (2015) Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice. Int J Obes 39(8):1292–1299. https://doi.org/10.1038/ijo.2015.52CrossRef

49.

Qiu Y, Nguyen KD, Odegaard JI et al (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157(6):1292–1308. https://doi.org/10.1016/j.cell.2014.03.066CrossRefPubMedPubMedCentral

50.

Scangas GA, Wu AW, Ting JY et al (2021) Cost utility analysis of dupilumab versus endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps. Laryngoscope 131(1):E26–E33. https://doi.org/10.1002/lary.28648CrossRefPubMed

Titel: Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature
verfasst von: Marella Reale
Giuseppe Licci
Pietro Orlando
Andrea Matucci
Franco Trabalzini
Giandomenico Maggiore
Oreste Gallo
Publikationsdatum: 19.05.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: European Archives of Oto-Rhino-Laryngology
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-024-08725-7

Neu im Fachgebiet HNO

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Hörschwäche erhöht Demenzrisiko unabhängig von Beta-Amyloid

29.05.2024 Hörstörungen Nachrichten

Hört jemand im Alter schlecht, nimmt das Hirn- und Hippocampusvolumen besonders schnell ab, was auch mit einem beschleunigten kognitiven Abbau einhergeht. Und diese Prozesse scheinen sich unabhängig von der Amyloidablagerung zu ereignen.

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

Betalaktam-Allergie: praxisnahes Vorgehen beim Delabeling

16.05.2024 Pädiatrische Allergologie Nachrichten

Die große Mehrheit der vermeintlichen Penicillinallergien sind keine. Da das „Etikett“ Betalaktam-Allergie oft schon in der Kindheit erworben wird, kann ein frühzeitiges Delabeling lebenslange Vorteile bringen. Ein Team von Pädiaterinnen und Pädiatern aus Kanada stellt vor, wie sie dabei vorgehen.

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature

Abstract

Introduction

Materials and methods

Results

Conclusion

Neu im Fachgebiet HNO

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Hörschwäche erhöht Demenzrisiko unabhängig von Beta-Amyloid

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

Betalaktam-Allergie: praxisnahes Vorgehen beim Delabeling

Update HNO

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Introduction

Materials and methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Neu im Fachgebiet HNO

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Hörschwäche erhöht Demenzrisiko unabhängig von Beta-Amyloid

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

Betalaktam-Allergie: praxisnahes Vorgehen beim Delabeling

Update HNO