medicina61巻13号

2024年12月発行

特集 喘息・COPDと関連疾患の重要知識Up-to-date

喘息・COPDの治療

重症喘息における生物学的製剤

著者： 北澤晴奈¹ 檜澤伸之¹

所属機関： ¹筑波大学附属病院呼吸器内科

ページ範囲：P.2246 - P.2252

文献概要

Point
◎生物学的製剤の導入の対象は重症喘息である．
◎成人喘息に対する生物学的製剤導入によって，症状，増悪，呼吸機能の改善，経口ステロイド薬の減量効果が示されている．
◎患者の基本病態に注目し，2型炎症に関連するバイオマーカー，併存疾患，患者背景を踏まえ，適切な生物学的製剤を選択する．

参考文献

1）日本アレルギー学会喘息ガイドライン専門部会（監），「喘息予防・管理ガイドライン2021」作成委員：喘息予防・管理ガイドライン2021．協和企画，2021

2）Nagase H, et al：Prevalence, disease burden, and treatment reality of patients with severe, uncontrolled asthma in Japan. Allergol Int 69：53-60, 2020 PMID 31311707

3）Settipane RA, et al：Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol 123：564-572.e3, 2019 PMID 31494235

4）Agache I, et al：EAACI Biologicals Guidelines-Recommendations for severe asthma. Allergy 76：14-44, 2021 PMID 32484954

5）日本アレルギー学会（監），「アレルギー総合診療のための分子標的治療の手引き」作成委員会（編）：アレルギー総合診療のための分子標的治療の手引き．日本アレルギー学会，2022

6）Moro K, et al：Innate production of T（H）2 cytokines by adipose tissue-associated c-Kit（＋）Sca-1（＋）lymphoid cells. Nature 463：540-544, 2010 PMID 20023630

7）Kabata H, et al：The group 2 innate lymphoid cell（ILC2）regulatory network and its underlying mechanisms. Immunol Rev 286：37-52, 2018 PMID 30294963

8）Tanaka J, et al：Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2-polarizing conditions. Clin Exp Allergy 39：89-100, 2009 PMID 19055649

9）Liu S, et al：Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma；The role of thymic stromal lymphopoietin. J Allergy Clin Immunol 141：257-268.e6, 2018 PMID 28433687

10）日本呼吸器学会 難治性喘息診断と治療の手引き第2版作成委員会（編）：難治性喘息診断と治療の手引き 第2版 2023．メディカルレビュー社，2023

11）MacGlashan DW Jr, et al：Down-regulation of Fc（epsilon）RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 158：1438-1445, 1997 PMID 9013989

12）Holgate S, et al：The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J Allergy Clin Immunol 115：459-465, 2005 PMID 15753888

13）Humbert M, 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 60：309-316, 2005 PMID 15679715

14）Ohta K, et al：Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma. Respirology 14：1156-1165, 2009 PMID 19909462

15）Hanania NA, et al：Exploring the effects of omalizumab in allergic asthma；An analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med 187：804-811, 2013 PMID 23471469

16）Casale TB, et al：Omalizumab effectiveness by biomarker status in patients with asthma；Evidence from PROSPERO, a prospective real-world study. J Allergy Clin Immunol Pract 7：156-164.e1, 2019 PMID 29800752

17）Bousquet J, et al：Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir Med 101：1483-1492, 2007 PMID 17339107

18）Laviolette M, et al：Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol 132：1086-1096.e5, 2013 PMID 23866823

19）Ortega HG, et al：Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371：1198-1207, 2014 PMID 25199059

20）Bleecker ER, et al：Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2agonists（SIROCCO）；A randomised, multicentre, placebo-controlled phase 3 trial. Lancet 388：2115-2127, 2016 PMID 27609408

21）FitzGerald JM, et al：Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma（CALIMA）；A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388：2128-2141, 2016 PMID 27609406

22）Ortega HG, et al：Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds；A secondary analysis of the DREAM and MENSA studies. Lancet Respir Med 4：549-556, 2016 PMID 27177493

23）FitzGerald JM, et al：Predictors of enhanced response with benralizumab for patients with severe asthma；Pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med 6：51-64, 2018 PMID 28919200

24）Chupp GL, et al：Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma（MUSCA）；A randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med 5：390-400, 2017 PMID 28395936

25）Bel EH, et al：Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371：1189-1197, 2014 PMID 25199060

26）Nair P, et al：Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med 376：2448-2458, 2017 PMID 28530840

27）Castro M, et al：Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 378：2486-2496, 2018 PMID 29782217

28）Rabe KF, et al：Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med 378：2475-2485, 2018 PMID 29782224

29）Menzies-Gow A, et al：Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med 384：1800-1809, 2021 PMID 33979488

30）Diver S, et al：Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma（CASCADE）；A double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med 9：1299-1312, 2021 PMID 34256031

31）Wechsler ME, et al：Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma（SOURCE）；A randomised, placebo-controlled, phase 3 study. Lancet Respir Med 10：650-660, 2022 PMID 35364018