Laryngorhinootologie 2021; 100(02): 134-145
DOI: 10.1055/a-1309-6631
CME-Fortbildung

Biologika: Neue Therapieoption bei schwerer chronisch polypöser Rhinosinusitis

Biologics: A New Option in Treatment of Severe Chronic Rhinosinusits with Nasal Polyps
Mandy Cuevas
,
Thomas Zahnert

Die chronische Rhinosinusitis (CRS) zählt mit einer Prävalenz von bis zu 12 % zu einer der häufigsten chronischen Erkrankungen. Die Betroffenen berichten über eine starke Einschränkung ihrer Lebensqualität und meist einen langen Leidensweg. Trotz der bisherigen Standardtherapie ist die Erkrankung oft nicht ausreichend kontrolliert. Der folgende Artikel beschreibt Indikationen und Durchführung einer neuen Therapieoption mit Biologika.

Abstract

Chronic rhinosinusitis (CRS) is defined as an inflammation of the nose and paranasal sinuses with prevalence of 10.9 % and by the presents of 2 or more symptoms, which last more than 12 weeks. The symptoms are nasal obstruction, nasal discharge (anterior/post nasal drip), facial pain or pressure and/or olfactory disorder. CRS has a high negative impact on an individual’s quality of life. The pathogenesis is multifactorial and complex. CRS has been subclassified into 2 groups: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Regarding further knowledge of the inflammatory pathway the primary CRS is considered by endotype dominance, either type 2 or non-type 2. 80 % of the CRSwNP reveals a type 2 inflammation. The proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in nasal polyp tissues pattern. CRSwNP is often refractory to medical and surgical management, especially in patients with asthma and aspirin intolerance. In most cases the control of the disease is a challenge. Patients with asthma but especially with Samter’s triad are significantly more likely to have a recurrence of nasal polyps and undergo a second surgery following recurrence. In patients with severe CRSwNP, in whom the current standard of care including topical and oral corticosteroids, antibiotics and surgical procedures fail to control the disease, biologics can open new perspectives in treatment. They allow avoiding the possible adverse events resulting from repeated use of systemic corticosteroids and surgery. These biologics have a high impact on type 2 immune reaction and lead to a reduction of IgE as well as of local mucosal eosinophil migration and activation, resulting in a significant effect on nasal polyps, smell, quality of life and asthma comorbidity.



Publication History

Article published online:
01 February 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Stuck BA, Beule A, Jobst D. et al Guideline for “rhinosinusitis”-long version: S2k guideline of the German College of General Practitioners and Family Physicians and the German Society for Oto-Rhino-Laryngology, Head and Neck Surgery. HNO 2018; 66 (01) 38-74
  • 2 Fokkens WJ, Lund VJ, Hopkins C. et al Executive summary of EPOS 2020 including integrated care pathways. Rhinology 2020; 58 (02) 82-111 . doi:10.4193/Rhin20.601
  • 3 Fokkens WJ, Lund VJ, Mullol J. et al EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 2012; 50 (01) 1-12 . doi:10.4193/Rhino50E2
  • 4 Ostovar A, Fokkens WJ, Vahdat K. et al Epidemiology of chronic rhinosinusitis in Bushehr, southwestern region of Iran: a GA2LEN study. Rhinology 2019; 57 (01) 43-48 . doi:10.4193/Rhin18.061. Ass
  • 5 Hirsch AG, Stewart WF, Sundaresan AS. et al Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample. Allergy 2017; 72 (02) 274-281 . doi:10.1111/all.13042. Epub 2016 Sep 19
  • 6 Kato A. Immunopathology of chronic rhinosinusitis. Allergol Int 2015; 64 (02) 121-130 . doi:10.1016/j.alit.2014.12.006. Epub 2015 Feb 9
  • 7 Garcia G, Taillé C, Laveneziana P. et al Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev 2013; 22 (129) 251-257 . doi:10.1183/09059180.00004013
  • 8 Mjosberg JM, Trifari S, Crellin NK. et al Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 2011; 12 (11) 1055-1062
  • 9 Ho J, Bailey M, Zaunders J. et al Group 2 innate lymphoid cells (ILC2s) are increased in chronic rhinosinusitis with nasal polyps or eosinophilia. Clin Exp Allergy 2015; 45 (02) 394-403
  • 10 Tomassen P, Vandeplas G, Van Zele T. et al Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol 2016; 137 (05) 1449-1456.e4
  • 11 Chong LY, Head K, Hopkins C. et al Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database Syst Rev 2016; 4: CD011996
  • 12 Smith TL, Sautter NB. Is montelukast indicated for treatment of chronic rhinosinusitis with polyposis?. Laryngoscope 2014; 124 (08) 1735-1736
  • 13 Umbreit C, Virchow JC, Thorn C. et al Analgetikaintoleranz. Internist 2010; 51: 1196-1201
  • 14 Li R, Luo F. Safety and Efficacy of Aspirin Desensitization Combined With Long-Term Aspirin Therapy in Aspirin-Exacerbated Respiratory Disease. J Investig Allergol Clin Immunol 2020; 30 (05) 327-333 . doi:10.18176/jiaci.0433. Epub 2019 Jul 8
  • 15 Mendelsohn D, Jeremic G, Wright ED. et al Revision rates after endoscopic sinus surgery: a recurrence analysis. Ann Otol Rhinol Laryngol 2011; 120 (03) 162-166 . doi:10.1177/000348941112000304
  • 16 GlaxoSmithKline GmbH & Co. KG. Nucala 100mg Injektionslösung in einer Fertigspritze, R.L.S. GmbH – Fachinformation. Frankfurt: Rote Liste Service GmbH; 2019 6.
  • 17 Bachert C, Sousa AR, Lund VJ. et al Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial. J Allergy Clin Immunol 2017; 140 (04) 1024-1031.e14
  • 18 GlaxoSmithKline plc. Nucala (mepolizumab) is the first anti-IL5 biologic to report positive phase 3 results in patients with nasal polyps (03.04.2020). Im Internet (Stand: 12.12.2020): www.gsk.com/en-gb/media/press-releases/nucala-mepolizumab-is-the-first-anti-il5-biologic-to-report-positive-phase-3-results-in-patients-with-nasal-polyps/
  • 19 AstraZeneca GmbH. Fasenra 30mg Injektionslösung in einer Fertigspritze, R.L.S. GmbH. Fachinformation. Frankfurt: Rote Liste Service GmbH; 2019 7.
  • 20 AstraZeneca. Fasenra met both co-primary endpoints of reduced nasal polyp size and blockage in the OSTRO Phase III trial for patients with chronic rhinosinusitis with nasal polyps (10.09.2020). Im Internet (Stand: 12.12.2020): www.astrazeneca.com/media-centre/press-releases/2020/fasenra-met-both-co-primary-endpoints-of-reduced-nasal-polyp-size-and-blockage-in-the-ostro-phase-iii-trial.html
  • 21 Teva BV. Cinqaero 10mg/ml, R.L.S. GmbH. Fachinformation. Frankfurt: Rote Liste Service GmbH; 2018
  • 22 Sanofi-Aventis Deutschland GmbH. Dupixent 300mg Injektionslösung in einer Fertigspritze, R.L.S. GmbH. Fachinformation. Frankfurt: Rote Liste Service GmbH; 2020 21.
  • 23 Bachert C, Mannent L, Naclerio RM. 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 (05) 469-479
  • 24 Bachert C, Han JK, Desrosiers M. et al 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 2019; 394: 1638-1650
  • 25 Novartis Pharma GmbH. Xolair 150mg Injektionslösung, R.L.S. GmbH. Fachinformation. Frankfurt: Rote Liste Service GmbH; 2019 9.
  • 26 Gevaert P, Calus L, Van Zele T. et al Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol 2013; 131 (01) 110-116.e1
  • 27 Gevaert P, Omachi TA, Corren J. et al Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol 2020; 146 (03) 595-605 . doi:10.1016/j.jaci.2020.05.032.Epub 2020 Jun 7
  • 28 Long A, Rahmaoui A, Rothman KJ. et al Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol 2014; 134 (03) 560-567.e4
  • 29 Fokkens WJ, Lund V, Bachert C. et al EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy 2019; 74 (12) 2312-2319
  • 30 Klimek L, Förster-Ruhrmann U, Becker S. et al Positionspapier: Anwendung von Biologika bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem – Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC). Laryngo-Rhino-Otologie 2020; 99 (08) DOI: 10.1055/a-1197-0136.