Skip to main content

Biologika beim schweren/schwierigen Asthma bronchiale im Kindes- und Jugendalter

Biologicals for severe/difficult bronchial asthma in childhood and adolescence


Das schwere therapierefraktäre Asthma bronchiale ist auch bei Kindern und Jugendlichen selten, stellt aber den Behandler vor besondere diagnostische und therapeutische Herausforderungen. Zunehmend werden im Rahmen der personalisierten Medizin verschiedene Phänotypen identifiziert, die eine individuelle Strategie erfordern. Mit der Verfügbarkeit von Biologika auch für Kinder und Jugendliche gibt es neue therapeutische Optionen. Diese Übersicht stellt die aktuell für Kinder und Jugendliche verfügbaren Biologika dar und gibt Entscheidungshilfen für ihren Einsatz.


Severe treatment refractory asthma is also rare in children and adolescents but represents a particular diagnostic and therapeutic challenge for the treating physician. Within the framework of personalized medicine various phenotypes are increasingly being identified that necessitate an individual strategy. The availability of innovative biologicals results in new therapeutic options also for children and adolescents. This review presents the biologicals currently available for children and adolescents and provides recommendations for their use.

This is a preview of subscription content, access via your institution.

Abb. 1
Abb. 2
Abb. 3


Verwendete Literatur

  1. 1.

    AMWF online (2020) Nationale Versorgungsleitlinie Asthma, 4. Aufl. (Version 1, AWMF-Register-Nr.: nvl-002)

    Google Scholar 

  2. 2.

    Bel EH, Wenzel SE, Thompson PJ et al (2014) Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371(13):1189–1197

    Google Scholar 

  3. 3.

    Berger W, Gupta N, McAlary M et al (2003) Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma. Ann Allergy Asthma Immunol 91(2):182–188

    CAS  PubMed  Google Scholar 

  4. 4.

    Brodlie M, McKean MC, Moss S et al (2012) The oral corticosteroid-sparing effect of omalizumab in children with severe asthma. Arch Dis Child 97(7):604–609

    PubMed  Google Scholar 

  5. 5.

    Busse WW, Morgan WJ, Gergen PJ et al (2011) Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 364(11):1005–1015

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Castro M, Corren J, Pavord ID et al (2018) Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 378(26):2486–2496

    CAS  PubMed  Google Scholar 

  7. 7.

    Chan R, RuiWen Kuo C, Lipworth B et al (2020) Pragmatic clinical perspective on biologics for severe refractory type 2 asthma. J Allergy Clin Immunol Pract 8(10):3363–3370

    PubMed  Google Scholar 

  8. 8.

    Chung KF, Wenzel SE, Brozek JL et al (2014) International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 43(2):343–373

    CAS  Google Scholar 

  9. 9.

    Deschildre A, Marguet C, Salleron J et al (2013) Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J 42(5):1224–1233

    CAS  PubMed  Google Scholar 

  10. 10.

    Deschildre A, Marguet C, Langlois C et al (2015) Real-life long-term omalizumab therapy in children with severe allergic asthma. Eur Respir J 46(3):856–859

    CAS  PubMed  Google Scholar 

  11. 11.

    European Medicines Agency (2021) Nucala. Zugegriffen: 23. Apr. 2021

  12. 12.

    Eyerich S, Metz M, Bossios A et al (2020) New biological treatments for asthma and skin allergies. Allergy 75(3):546–560

    PubMed  Google Scholar 

  13. 13.

    Farne HA, Wilson A, Powell C et al (2017) Anti-IL5 therapies for asthma. Cochrane Database Syst Rev 9:CD10834

    PubMed  Google Scholar 

  14. 14.

    Fitzpatrick AM (2016) Severe asthma in children: lessons learned and future directions. J Allergy Clin Immunol Pract 4(1):11–19

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Fleming L, Murray C, Bansal AT et al (2015) The burden of severe asthma in childhood and adolescence: results from the paediatric U‑BIOPRED cohorts. Eur Respir J 46(5):1322–1333

    CAS  PubMed  Google Scholar 

  16. 16.

    Flood-Page P, Swenson C, Faiferman I et al (2007) A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 176(11):1062–1071

    CAS  PubMed  Google Scholar 

  17. 17.

    Gupta A, Pouliquen I, Austin D et al (2019) Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma. Pediatr Pulmonol 54(12):1957–1967

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Henriksen DP, Bodtger U, Sidenius K et al (2018) Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL‑5 treatments of severe asthma—a systematic review and meta-analysis. Eur Clin Respir J 5(1):1536097

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Holguin F, Cardet JC, Chung KF et al (2020) Management of severe asthma: a European respiratory society/American thoracic society guideline. Eur Respir J 55(1):1900588

    CAS  PubMed  Google Scholar 

  20. 20.

    Licari A, Marseglia A, Caimmi S et al (2014) Omalizumab in children. Paediatr Drugs 16(6):491–502

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Licari A, Marseglia G, Castagnoli R et al (2015) The discovery and development of omalizumab for the treatment of asthma. Expert Opin Drug Discov 10(9):1033–1042

    PubMed  Google Scholar 

  22. 22.

    Licari A, Castagnoli R, Denicolo C et al (2017a) Omalizumab in children with severe allergic asthma: the Italian real-life experience. Curr Respir Med Rev 13(1):36–42

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Licari A, Castagnoli R, Denicolò CF et al (2017b) The nose and the lung: united airway disease? Front Pediatr 5:44

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Licari A, Brambilla I, Marseglia A et al (2018a) Difficult vs. severe asthma: definition and limits of asthma control in the pediatric population. Front Pediatr 6:170

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Licari A, Castagnoli R, Brambilla I et al (2018b) Asthma endotyping and biomarkers in childhood asthma. Pediatr Allergy Immunol Pulmonol 31(2):44–55

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Licari A, Manti S, Chiappini E et al (2020) Severe asthma in children: current goals and unmet needs. Pediatr Allergy Immunol 31(24):40–42

    PubMed  Google Scholar 

  27. 27.

    Long A, Rahmaoui A, Rothman KJ et al (2014) Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol 134(3):560–567

    CAS  PubMed  Google Scholar 

  28. 28.

    Manka LA, Wechsler ME (2018) New biologics for allergic diseases. Expert Rev Clin Immunol 14(4):285–296

    CAS  PubMed  Google Scholar 

  29. 29.

    Manti S, Brown P, Perez MK et al (2017) The role of neurotrophins in inflammation and allergy. Vitam Horm 104:313–341

    CAS  PubMed  Google Scholar 

  30. 30.

    Maspero J, Fitzgerald M, Pavord I et al (2018) Dupilumab reduces severe exacerbation rate and improves lung function in adolescent patients with uncontrolled, moderate-to-severe asthma: from the liberty asthma quest study. Chest 154(4):25A–27A

    Google Scholar 

  31. 31.

    Miraglia Del Giudice M, Marseglia GL, Leonardi S et al (2011) Fractional exhaled nitric oxide measurements in rhinitis and asthma in children. Int J Immunopathol Pharmacol 24(4):29–32

    CAS  PubMed  Google Scholar 

  32. 32.

    Montalbano L, Ferrante G, Montella S et al (2020) Relationship between quality of life and behavioural disorders in children with persistent asthma: a multiple indicators multiple causes (MIMIC) model. Sci Rep 10(1):6957

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Montella S, Baraldi E, Cazzato S et al (2016) Severe asthma features in children: a case-control online survey. Ital J Pediatr 42(1):9

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Mukherjee M, Nair P (2015) Blood or sputum eosinophils to guide asthma therapy? Lancet Respir Med 3(11):824–825

    PubMed  Google Scholar 

  35. 35.

    NICE (2017) Mepolizumab for treating severe refractory eosinophilic asthma. Zugegriffen: 22. Febr. 2021

  36. 36.

    Rabe KF, Nair P, Brusselle G et al (2018) Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med 378(26):2475–2485

    CAS  PubMed  Google Scholar 

  37. 37.

    Ramratnam SK, Bacharier LB, Guilbert TW (2017) Severe asthma in children. J Allergy Clin Immunol Pract 5(4):889–898

    PubMed  Google Scholar 

  38. 38.

    Rusconi F, Fernandes RM, Pijnenburg MWH et al (2018) The severe paediatric asthma collaborative in Europe (SPACE) ERS clinical research collaboration: enhancing participation of children with asthma in therapeutic trials of new biologics and receptor blockers. Eur Respir J 52(4):1801665

    PubMed  Google Scholar 

  39. 39.

    Russo D, Di Filippo P, Attanasi M, Lizzi M, Di Pillo S, Chiarelli F (2021) Biologic therapy and severe asthma in children. Biomedicines 9:760.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Sanofi (2015) Evaluation of dupilumab in patients with persistent asthma (Liberty asthma quest). Zugegriffen: 22. Febr. 2021

  41. 41.

    Sanofi (2015) Evaluation of dupilumab in patients with severe steroid dependent asthma (VENTURE). Zugegriffen: 22. Febr. 2021

  42. 42.

    Santini G, Mores N, Malerba M et al (2017) Dupilumab for the treatment of asthma. Expert Opin Investig Drugs 26(3):357–366

    CAS  PubMed  Google Scholar 

  43. 43.

    Shepard HM, Phillips GL, Thanos CD, Feldmann M (2017) Developments in therapy with monoclonal antibodies and related proteins. Clin Med 17:220–232

    Google Scholar 

  44. 44.

    Sorkness CA, Wildfire JJ, Calatroni A et al (2013) Reassessment of omalizumab-dosing strategies and pharmacodynamics in inner-city children and adolescents. J Allergy Clin Immunol Pract 1(2):163–171

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Teach SJ, Gill MA, Togias A et al (2015) Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol 136(6):1476–1485

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Votto M, De Filippo M, Licari A, Marseglia A, De Amici M, Marseglia GL (2021) Biological therapies in children and adolescents with severe uncontrolled asthma: a practical review. Biol Targets Ther 15:133–142

    Google Scholar 

  47. 47.

    Wenzel S, Castro M, Corren J et al (2016) Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to high-dose inhaled corticosteroids plus a long-acting β2 agonist: a rando-mised double-blind placebo-controlled pivotal phase 2b doseranging trial. Lancet 388(10039):31–44

    CAS  PubMed  Google Scholar 

Weiterführende Literatur

  1. 48.

    Busse W, Buhl R, Fernandez Vidaurre C et al (2012) Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol 129(4):983–989

    CAS  PubMed  Google Scholar 

  2. 49.

    Busse WW, Maspero JF, Rabe KF et al (2018) Liberty asthma QUEST: phase 3 randomized, double-blind, placebo-controlled, parallel-group study to evaluate dupilumab efficacy/safety in patients with uncontrolled, moderate-to-severe asthma. Adv Ther 35(5):737–748

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 50.

    Chipps BE, Lanier B, Milgrom H et al (2017) Omalizumab in children with uncontrolled allergic asthma: review of clinical trial and real-world experience. J Allergy Clin Immunol 139(5):1431–1444

    CAS  PubMed  Google Scholar 

  4. 51.

    Drick N, Seeliger B, Welte T et al (2018) Anti-IL‑5 therapy in patients with severe eosinophilic asthma-clinical efficacy and possible criteria for treatment response. BMC Pulm Med 18(1):119

    PubMed  PubMed Central  Google Scholar 

  5. 52.

    European Medicines Agency Dupilumab summary of product characteristics. Zugegriffen: 22. Febr. 2021

  6. 53.

    Global Initiative for Asthma (2020) Global strategy for asthma management and prevention. Zugegriffen: 22. Febr. 2021

  7. 54.

    Goulet DR, Atkins WM (2020) Considerations for the design of antibody-based therapeutics. J Pharm Sci 109:74–103

    CAS  PubMed  Google Scholar 

  8. 55.

    GSK European commission approves nucala (mepolizumab) for the treatment of children with severe asthma. Zugegriffen: 22. Febr. 2021

  9. 56.

    Haldar P (2017) Patient profiles and clinical utility of mepolizumab in severe eosinophilic asthma. Biologics 11:81–95.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 57.

    Lanier B, Bridges T, Kulus M et al (2009) Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol 124(6):1210–1216

    CAS  PubMed  Google Scholar 

  11. 58.

    Licari A, Brambilla I, De Filippo M et al (2017) The role of upper airway pathology as a comorbidity in severe asthma. Expert Rev Respir Med 11(11):855–865

    CAS  PubMed  Google Scholar 

  12. 59.

    Licari A, Manti S, Castagnoli R et al (2019) Targeted therapy for severe asthma in children and adolescents: current and future perspectives. Paediatr Drugs 21(4):215–237

    PubMed  Google Scholar 

  13. 60.

    Little M, Kipriyanov S, Le Gall F, Moldenhauer G (2000) Of mice and men: hybridoma and recombinant antibodies. Immunol Today 21:364–370

    CAS  PubMed  Google Scholar 

  14. 61.

    Lugogo N, Domingo C, Chanez P et al (2016) Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther 38(9):2058–2070

    CAS  PubMed  Google Scholar 

  15. 62.

    Milgrom H, Fowler-Taylor A, Vidaurre CF et al (2011) Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma. Curr Med Res Opin 27(1):163–169

    CAS  PubMed  Google Scholar 

  16. 63.

    Normansell R, Walker S, Milan SJ et al (2014) Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 1:CD3559

    Google Scholar 

  17. 64.

    Ortega H, Llanos JP, Lafeuille MH et al (2019) Effects of systemic corticosteroids on blood eosinophil counts in asthma: real-world data. J Asthma 56(8):808–815

    CAS  PubMed  Google Scholar 

  18. 65.

    Ortega HG, Liu MC, Pavord ID et al (2014) Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371(13):1198–1207

    Google Scholar 

  19. 66.

    Pavord ID, Kom S, Howarth P et al (2012) Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380(9842):651–659

    CAS  Google Scholar 

  20. 67.

    Pitrez PM, de Souza RG, Roncada C et al (2017) Impact of omalizumab in children from a middle-income country with severe therapy-resistant asthma: a real-life study. Pediatr Pulmonol 52(11):1408–1413

    PubMed  Google Scholar 

  21. 68.

    Rodrigo GJ, Neffen H (2015) Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents. Pediatr Allergy Immunol 26(6):551–556

    PubMed  Google Scholar 

  22. 69.

    Samitas K, Zervas E, Gaga M (2017) T2-low asthma: current approach to diagnosis and therapy. Curr Opin Pulm Med 23(1):48–55

    CAS  PubMed  Google Scholar 

  23. 70.

    Sesé L, Schneider M, Bourgoin M et al (2019) Asthma with multiple allergic comorbidities is associated with complete response to omalizumab. Clin Exp Allergy 49(5):733

    PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Markus A. Rose MPH.

Ethics declarations


M.A. Rose hat von GSK, Sanofi Aventis und Novartis finanzielle Unterstützung für wissenschaftliche Projekte, Kongressteilnahmen und Rednerhonorare erhalten. Dies hat keinen Einfluss auf die Inhalte dieser Arbeit

Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information


QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rose, M.A. Biologika beim schweren/schwierigen Asthma bronchiale im Kindes- und Jugendalter. Pneumologe 18, 395–404 (2021).

Download citation


  • Omalizumab
  • Mepolizumab
  • Dupilumab
  • Personalisierte Medizin
  • Phänotypen


  • Omalizumab
  • Mepolizumab
  • Dupilumab
  • Personalized medicine
  • Phenotypes