Biologika bei chronischer Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal mucosa, lasting for more than 12 weeks. By now approximately 15 % of the European and American population are affected, which indicates that CRS is a serious health problem. Beside other subgroups the most important classification is CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). Standard-of-care therapies include nasal saline solution as well as topic or systemic corticosteroids. If this does not lead to a sufficient recovery, surgical therapy is a good option. A new therapy option is represented by biologics, particularly monoclonal antibodies (mAB). They are well-established for treatment of asthma bronchiale. Due to the fact that asthma is often associated with nasal polyps, and mAB may could also lead to improvements in CRS, studies were conducted. In the meantime there is a number of mAB which have emerged as an alternative treatment for patients with CRSwNP.

Die Basistherapie der chronischen Rhinosinusitis (CRS) beinhaltet Nasenspülungen und nasale sowie ggf. systemische Kortikosteroide. Kann damit keine ausreichende Besserung erzielt werden, ist die chirurgische Behandlung eine Option. Eine neue Therapieoption bei eosinophiler CRSwNP sind Biologika. Dieser Beitrag gibt eine Übersicht über aktuell zugelassene oder in klinischer Prüfung befindliche Biologika, für die Daten zur CRS vorliegen.

Schlüsselwörter

chronische Rhinosinusitis - Therapie - Biologika - monoklonale Antikörper - Nasennebenhöhlenentzündung - Nasenpolypen

Key words

chronic rhinosinusitis - therapy - biologics - monoclonal antibody - nasal polyps

Publication History

Article published online:
25 June 2020

• Literatur

• 1 Tsetsos N, Goudakos JK, Daskalakis D. et al. Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review. Rhinology 2018; 56: 11-21
• 2 Fokkens WJ, Lund VJ, Mullol J. et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl 2012; 23 (03) 1-298
• 3 Orlandi RR, Kingdom TT, Hwang PH. et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol 2016; 6 (Suppl. 01) S22-209
• 4 Koennecke M, Klimek L, Mullol J. et al. Subtyping of polyposis nasi: phenotypes, endotypes and comorbidities. Allergo J Int 2018; 27: 56-65
• 5 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: 1024-1031; e14
• 6 Klimek L, Koennecke M, Hagemann J. et al. [Immunology of chronic rhinosinusitis with nasal polyps as a basis for treatment with biologicals]. HNO 2019; 67: 15-26
• 7 Stuck BA, Beule A, Jobst D. et al. Leitlinie „Rhinosinusitis“ – Langfassung. HNO 2018; 66: 38-74
• 8 Riechelmann H. Chronische Rhinosinusitis – EPOS 2012 Teil I. Laryngo-Rhino-Otol 2013; 92: 193-201 ; quiz 202–203
• 9 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: 469-479
• 10 Gevaert P, Van Bruaene N, Cattaert T. et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol 2011; 128: 989-995; e1–e8
• 11 Riechelmann H, Deutschle T, Rozsasi A. et al. Nasal biomarker profiles in acute and chronic rhinosinusitis. Clin Exp Allergy 2005; 35: 1186-1191
• 12 Chiarella SE, Sy H, Peters AT. Monoclonal antibody therapy in sinonasal disease. Am J Rhinol Allergy 2017; 31: 93-95
• 13 Dejaco D, Riedl D, Giotakis A. et al. Treatment Outcomes in Chronic Rhinosinusitis Refractory to Maximal Medical Therapy: A Prospective Observational Study Under Real-World Conditions. Ear Nose Throat J 2019;
• 14 Milonski J, Zielinska-Blizniewska H, Majsterek I. Expression of POSTN, IL-4, and IL-13 in Chronic Rhinosinusitis with Nasal Polyps. DNA Cell Biol 2015; 34: 342-349
• 15 Kumagai N, Fukuda K, Fujitsu Y. et al. Synergistic effect of TNF-alpha and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts. Cornea 2003; 22: 557-561
• 16 Provost V, Langlois A, Chouinard F. et al. Leukotriene D4 and interleukin-13 cooperate to increase the release of eotaxin-3 by airway epithelial cells. PloS one 2012; 7: e43544
• 17 Nabavi M, Arshi S, Bahrami A. et al. Increased level of interleukin-13, but not interleukin-4 and interferon-gamma in chronic rhinosinusitis with nasal polyps. Allergol Immunopathol (Madr) 2014; 42: 465-471
• 18 Wise SK, Den Beste KA, Hoddeson EK. et al. Sinonasal epithelial wound resealing in an in vitro model: inhibition of wound closure with IL-4 exposure. Int Forum Allergy Rhinol 2013; 3: 439-449
• 19 Steinke JW, Payne SC, Borish L. Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization. J Allergy (Cairo) 2012; 2012: 182090
• 20 Chames P, Van Regenmortel M, Weiss E. et al. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol 2009; 157: 220-233
• 21 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: 110-116; e1
• 22 Tajiri T, Matsumoto H, Hiraumi H. et al. Efficacy of omalizumab in eosinophilic chronic rhinosinusitis patients with asthma. Ann Allergy Asthma Immunol 2013; 110: 387-388
• 23 Pinto JM, Mehta N, Di Tineo M. et al. Naclerio, A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology 2010; 48: 318-324
• 24 Walsh GM. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions. Current opinion in molecular therapeutics 2009; 11: 329-336
• 25 Gevaert P, Lang-Loidolt D, Lackner A. et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol 2006; 118: 1133-1141
• 26 Man LX. Study of Chronic Rhinosinusitis Symptoms in Asthma Patients Undergoing Treatment With Reslizumab. Im Internet: https://clinicaltrials.gov/ct2/show/NCT03369574
• 27 Jacob JS. Effect of Reslizumab in Chronic Rhinosinusitis. Im Internet: https://clinicaltrials.gov/ct2/show/NCT02799446
• 28 Nair P, Wenzel S, Rabe KF. et al. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med 2017; 376: 2448-2458
• 29 Johns Hopkins University. Benralizumab Effect on Severe Chronic Rhinosinusitis With Eosinophilic Polyposis. Im Internet: https://clinicaltrials.gov/ct2/show/NCT03450083
• 30 Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis (OSTRO). Im Internet: https://clinicaltrials.gov/ct2/show/NCT03401229
• 31 Shirley M. Dupilumab: First Global Approval. Drugs 2017; 77: 1115-1121
• 32 Jonstam K, Swanson BN, Mannent LP. et al. Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis. Allergy 2019; 74: 743-752
• 33 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
• 34 Braddock M, Hanania NA, Sharafkhaneh A. et al. Potential Risks Related to Modulating Interleukin-13 and Interleukin-4 Signalling: A Systematic Review. Drug Saf 2018; 41: 489-509