The Korean Journal of Medicine

  • 제80권2호
  • /
  • Pages.139-144
  • /
  • 2011
  • /
  • 1738-9364(pISSN)
  • /
  • 2289-0769(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
권호 표지

새로운 천식 치료제

New Therapeutic Modalities for Asthma: Biologicals from a Practical Point of View

  • 장윤석 (서울대학교 의과대학 내과학교실)
  • Chang, Yoon-Seok (Department of Internal Medicine, Seoul National University College of Medicine)
  • 발행 : 2011.02.01
⟨ 이전 논문 다음 논문 ⟩

초록

Asthma is a representative allergic disease of chronic airway inflammation. Dyspnea, wheezing, cough, and chest tightness are typical symptoms. Treatment consists of inhaled corticosteroid, $\beta2$ agonist, leukotriene modifiers, and xanthines such as theophylline. Clinical practice guidelines for asthma have been developed since early 1990s. However, there are still many uncontrolled asthma patients with severe refractory symptoms, frequent exacerbations and even mortality. These patients cause high socioeconomic burden but the management of these patients are not well covered by clinical practice guidelines. High-dose steroid, methotrexate, cyclosporine, gold, IVIG, and macrolides have been suggested as therapeutic modalities for refractory asthma but with limited treatment effect and side effects. It is necessary to develop new therapeutic modalities for asthma. Biologicals, or biologics, are a variety of protein-based therapeutics, e.g. antibodies, soluble receptors, recombinant protein-based receptor antagonists and other related structures. New biologicals for the treatment of asthma are being developed. Here I will focus on three biologicals from a practical point of view: a humanized monoclonal anti-IgE antibody (omalizumab), anti-IL5, and TNF-$\alpha$ antagonist.

키워드

참고문헌

  1. 조상헌, 김윤근, 장윤석, 김선신, 민경업, 김유영. 우리나라 기관지천식에 대한 인지 및 실태조사. 대한내과학회지 2006;70:69-77.
  2. 장윤석. 기관지천식의 진료 지침. 제1회 분당서울대학교병원 내과 연수강좌. 2003.
  3. 만성기도폐쇄성질환 임상연구센터, 대한천식알레르기학회. 한국성인천식의 진료지침. 2007 (www.allergy.or.kr).
  4. 장윤석. 중증 알레르기질환에 사용하는 스테로이드와 면역억제제. 제32차 대한천식및알레르기학회 교육강좌. 천식 및 알레르기 2008;S48-54.
  5. Cook ML, Bochner BS. Update on Biological Therapeutics for Asthma. World Allergy Organiz J 2010;3:188-194.
  6. 강혜련. 새로운 천식 치료제: 항 IgE 항체. 제32차 대한천식및 알레르기학회 교육강좌. 천식 및 알레르기 2008;S27-34.
  7. Holgate ST. A brief history of asthma and its mechanisms to modern concepts of disease pathogenesis. Allergy Asthma Immunol Res 2010;2:165-171. https://doi.org/10.4168/aair.2010.2.3.165
  8. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001;108:184-190. https://doi.org/10.1067/mai.2001.117880
  9. Nowak D, Management of asthma with anti-immunoglobulin E: a review of clinical trials of omalizumab. Respir Med 2006;100:1907-1917. https://doi.org/10.1016/j.rmed.2005.10.004
  10. Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005;60:309-316. https://doi.org/10.1111/j.1398-9995.2004.00772.x
  11. Korn S, Thielen A, Seyfried S, Taube C, Kornmann O, Buhl R. Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany. Respir Med 2009;103:1725-1731. https://doi.org/10.1016/j.rmed.2009.05.002
  12. Brown R, Turk F, Dale P, Bousquet J. Cost-effectiveness of omalizumab in patients with severe persistent allergic asthma. Allergy 2007;62:149-153.
  13. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol 2007;102:1378-1381.
  14. FDA. Medication guide $XOLAIR^{(R)}$ (omalizumab). Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/103976s5102mg.pdf. Accessed Jan 28, 2011.
  15. FDA. Early Communication about an Ongoing Safety Review of Omalizumab (marketed as Xolair). Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm172218.htm. Accessed Jan 28, 2011.
  16. Zuberbier T, Asero R, Bindslev-Jensen C, et al. Dermatology Section of the European Academy of Allergology and Clinical Immunology; Global Allergy and Asthma European Network; European Dermatology Forum; World Allergy Organization. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy 2009;64:1427-1443. https://doi.org/10.1111/j.1398-9995.2009.02178.x
  17. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:985-993. https://doi.org/10.1056/NEJMoa0805435
  18. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone- dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-993. https://doi.org/10.1056/NEJMoa0805435
  19. Park HW, Shin ES, Lee JE, et al. Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction. Thorax 2007;62:265-269. https://doi.org/10.1136/thx.2006.065482
  20. Howarth PH, Babu KS, Arshad HS, et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005;60:1012-1018. https://doi.org/10.1136/thx.2005.045260
  21. Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697-708. https://doi.org/10.1056/NEJMoa050580
  22. Morjaria JB, Chauhan AJ, Babu KS, Polosa R, Davies DE, Holgate ST. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 2008;63:584-591. https://doi.org/10.1136/thx.2007.086314
  23. Holgate ST, Noonan M, Chanez P, et al. Efficacy/safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J 2010 Nov 25. (Epub head of print)
  24. Erin EM, Leaker BR, Nicholson GC, et al. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med 2006;174:753-762. https://doi.org/10.1164/rccm.200601-072OC
  25. Wenzel SE, Barnes PJ, Bleecker ER, et al. T03 Asthma Investigators. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 2009;179:549-558. https://doi.org/10.1164/rccm.200809-1512OC