基于机制研究的支气管哮喘靶向药物治疗进展
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摘要
近年来,随着支气管哮喘发病机制相关信号通路研究的不断深入,基于其机制研发了一些新的靶向药物。这些药物正逐步进入临床研究阶段,部分药物已经通过临床试验,最终进入临床使用,给临床医师带来更多的精准治疗的选择。本文将从支气管哮喘的病理生理机制、不同信号通路的功能的角度,对靶向药物在支气管哮喘中的应用做一系统综述,以期加深对靶向药物作用机制的理解,并为临床工作中治疗方案的选择提供参考和依据。
With the deep research on the mechanism of asthma, especially its related signal pathway, lots of new antibody drugs entered into clinical research stage, some of which had passed the clinical trials and finally come into the process of clinical usage. Here, we focus on the different signal pathways involved in pathophysiology process of asthma, the targets of the antibody drugs design, and the key points which could affect the clinical usage. This article has summarized the features of designed antibody drugs in order to help clinicians to understand the mechanism of the new drugs on markets and provid novel choice in clinical practice.
With the deep research on the mechanism of asthma, especially its related signal pathway, lots of new antibody drugs entered into clinical research stage, some of which had passed the clinical trials and finally come into the process of clinical usage. Here, we focus on the different signal pathways involved in pathophysiology process of asthma, the targets of the antibody drugs design, and the key points which could affect the clinical usage. This article has summarized the features of designed antibody drugs in order to help clinicians to understand the mechanism of the new drugs on markets and provid novel choice in clinical practice.
引文
[1]Bateman E D, Hurd S S, Barnes P J, et al. Global strategy for asthma management and prevention:GINA executive summary[J]. EurRespir J,2008,34(1):143-178.
[2] Wenzel S E. Asthma phenotypes:the evolution from clinical to molecular approaches[J]. Nature Medicine,2012,18:716.
[3] Chen S, Golam S, Myers J, et al. Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment[J]. Curr Med Res Opin,2018,34(12):2075-2088.
[4] Tabatabaian F,Ledford D K. Omalizumab for severe asthma:toward personalized treatment based on biomarker profile and clinical history[J]. J Asthma Allergy,2018,11:53-61.
[5] Lanier B Q, Corren J, Lumry W, et al. Omalizumab is effective in the long-term control of severe allergic asthma[J]. Ann Allergy Asthma Immunol,2003,91(2):154-159.
[6] Busse W, Corren J, Lanier B Q,et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma[J]. J Allergy Clin Immunol, 2001,108(2):184-190.
[7]Khatri S, Moore W, Gibson P G, et al. Assessment of the longterm safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma[J]. J Allergy Clin Immunol,2018. doi:10. 1016/j. jaci.2018.09.033.
[8] Emma R,Morjaria J B,Fuochi V,et al. Mepolizumab in the management of severe eosinophilic asthma in adults:current evidence and practical experience[J]. Ther Adv Respir Dis, 2018,12:1753466618808490.
[9] Poulakos M N, Cargill S M, Waineo M F, et al. Mepolizumab for the treatment of severe eosinophilic asthma[J]. Am J Health Syst Pharm,2017,74(13):963-969.
[10] Fajt M L, Wenzel S E. Biologic therapy in asthma:entering the new age of personalized medicine[J]. J Asthma,2014,51(7):669-676.
[11] Strauss R A, Jawhari N. Mepolizumab in the treatment of severe eosinophilic asthma:results from a physician in the field[J]. Ann Allergy Asthma Immunol,2018,121(1):121-123.
[12] Mepolizumab treatment in patients with severe eosinophilic asthma[J].N Engl J Med,2015,372(18):1777.
[13] McCallister J W. Reslizumab and eosinophilic asthma:one step closer to phenotype-directed therapy[J]. Am J Respir Crit Care Med,2011,184(10):1096-1097.
[14] Corren J, Weinstein S,Janka L,et al. Phase 3 Study of reslizumab in patients with poorly controlled asthma:effects across a broad range of eosinophil counts[J]. Chest,2016,150(4):799-810.
[15] Murphy K,Jacobs J,Bjermer L,et al. Long-term safety and efficacy of reslizumab in patients with eosinophilic asthma[J]. J Allergy Clin Immunol Pract,2017,5(6):1572-1581,e1573.
[16] Casale T B,Pacou M,Mesana L,et al. Reslizumab compared with benralizumab in patients with eosinophilic asthma:a systematic literature review and network meta-analysis[J]. J Allergy Clin Immunol Pract,2019,7(1):122-130, el.
[17](O|¨)ztürk Aktas O, Sekerel B E, Kalyoncu A F. Glucocorticoid sparing of benralizumab in asthma[J]. N Engl J Med, 2017,377(12):1204-1205.
[18] Busse W W, Maspero J F, Rabe K F, et al. 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[J]. Adv Ther,2018. doi:10. 1007/s12325-018-0702-4.
[19] Castro M, Corren J, Pavord I D, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma[J]. N Engl J Med,2018,378(26):2486-2496.
[20] Hanania N A,Korenblat P, Chapman K R,et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma(LAVOLTA I and LAVOLTA II):replicate, phase 3, randomised,double-blind,placebo-controlled trials[J]. Lancet Respir Med,2016,4(10):781-796.
[21] Chung K F. Tralokinumab unsuccessful for management of severe,uncontrolled asthma[J]. Lancet Respir Med, 2018,6(7):480-481.
[22] Corren J, Parnes J R, Wang L, et al. Tezepelumab in adults with uncontrolled asthma[J]. N Engl J Med, 2017, 377(10):936-946.
[2] Wenzel S E. Asthma phenotypes:the evolution from clinical to molecular approaches[J]. Nature Medicine,2012,18:716.
[3] Chen S, Golam S, Myers J, et al. Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment[J]. Curr Med Res Opin,2018,34(12):2075-2088.
[4] Tabatabaian F,Ledford D K. Omalizumab for severe asthma:toward personalized treatment based on biomarker profile and clinical history[J]. J Asthma Allergy,2018,11:53-61.
[5] Lanier B Q, Corren J, Lumry W, et al. Omalizumab is effective in the long-term control of severe allergic asthma[J]. Ann Allergy Asthma Immunol,2003,91(2):154-159.
[6] Busse W, Corren J, Lanier B Q,et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma[J]. J Allergy Clin Immunol, 2001,108(2):184-190.
[7]Khatri S, Moore W, Gibson P G, et al. Assessment of the longterm safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma[J]. J Allergy Clin Immunol,2018. doi:10. 1016/j. jaci.2018.09.033.
[8] Emma R,Morjaria J B,Fuochi V,et al. Mepolizumab in the management of severe eosinophilic asthma in adults:current evidence and practical experience[J]. Ther Adv Respir Dis, 2018,12:1753466618808490.
[9] Poulakos M N, Cargill S M, Waineo M F, et al. Mepolizumab for the treatment of severe eosinophilic asthma[J]. Am J Health Syst Pharm,2017,74(13):963-969.
[10] Fajt M L, Wenzel S E. Biologic therapy in asthma:entering the new age of personalized medicine[J]. J Asthma,2014,51(7):669-676.
[11] Strauss R A, Jawhari N. Mepolizumab in the treatment of severe eosinophilic asthma:results from a physician in the field[J]. Ann Allergy Asthma Immunol,2018,121(1):121-123.
[12] Mepolizumab treatment in patients with severe eosinophilic asthma[J].N Engl J Med,2015,372(18):1777.
[13] McCallister J W. Reslizumab and eosinophilic asthma:one step closer to phenotype-directed therapy[J]. Am J Respir Crit Care Med,2011,184(10):1096-1097.
[14] Corren J, Weinstein S,Janka L,et al. Phase 3 Study of reslizumab in patients with poorly controlled asthma:effects across a broad range of eosinophil counts[J]. Chest,2016,150(4):799-810.
[15] Murphy K,Jacobs J,Bjermer L,et al. Long-term safety and efficacy of reslizumab in patients with eosinophilic asthma[J]. J Allergy Clin Immunol Pract,2017,5(6):1572-1581,e1573.
[16] Casale T B,Pacou M,Mesana L,et al. Reslizumab compared with benralizumab in patients with eosinophilic asthma:a systematic literature review and network meta-analysis[J]. J Allergy Clin Immunol Pract,2019,7(1):122-130, el.
[17](O|¨)ztürk Aktas O, Sekerel B E, Kalyoncu A F. Glucocorticoid sparing of benralizumab in asthma[J]. N Engl J Med, 2017,377(12):1204-1205.
[18] Busse W W, Maspero J F, Rabe K F, et al. 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[J]. Adv Ther,2018. doi:10. 1007/s12325-018-0702-4.
[19] Castro M, Corren J, Pavord I D, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma[J]. N Engl J Med,2018,378(26):2486-2496.
[20] Hanania N A,Korenblat P, Chapman K R,et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma(LAVOLTA I and LAVOLTA II):replicate, phase 3, randomised,double-blind,placebo-controlled trials[J]. Lancet Respir Med,2016,4(10):781-796.
[21] Chung K F. Tralokinumab unsuccessful for management of severe,uncontrolled asthma[J]. Lancet Respir Med, 2018,6(7):480-481.
[22] Corren J, Parnes J R, Wang L, et al. Tezepelumab in adults with uncontrolled asthma[J]. N Engl J Med, 2017, 377(10):936-946.