非甾体类抗炎药（NSAID）诱导呼吸道疾病患者的生物治疗后NSAID耐受性研究：一项随机比较试验
2023/07/21
摘要
背景：目前尚无前瞻性研究比较生物治疗如何影响非甾体抗炎药（NSAID）诱导呼吸道疾病中的NSAID耐受性。
目的：本研究旨在研究生物治疗如何诱导NSAID诱导呼吸道疾病患者的NSAID耐受性。
方法：本研究在现实世界的临床环境中，对罹患重症哮喘和2型炎症的受试者进行前瞻性试点研究。随机分配治疗方案：贝那利珠单抗、度普利尤单抗、美泊利珠单抗或奥马珠单抗 。通过乙酰水杨酸（ASA-OCT）口服激发试验（OCT）证实NSAID不耐受。主要结果是在每次6个月生物治疗前后基于OCT的NSAID耐受性（组内比较）。作为探索性结果，本研究比较了生物治疗之间的NSAID耐受性（组间比较）。
结果：本研究共纳入38名受试者，其中9人接受贝那利珠单抗、10人接受度普利尤单抗、9人接受美泊利珠单抗和10人接受奥马珠单抗治疗。在ASA-OCT中，奥马珠单抗（P<.001）和度普利尤单抗（P=.004）组产生反应所需的浓度增加，但美泊利珠单抗和贝那利珠单抗无增加。奥马珠单抗和度普利尤单抗获得NSAID耐受的频率最高（奥马珠单抗60%，度普利尤单抗40%，美泊利珠单抗22%，贝那利珠单抗22%）。
结论：哮喘的生物治疗有助于诱导NSAID耐受。然而在2型炎症和总IgE、特应性和嗜酸性粒细胞水平高的患者中，抗IgE或抗IL4/13似乎比抗嗜酸性粒细胞治疗更有效。奥马珠单抗和度普利尤单抗可提高ASA耐受性，而美泊利珠单抗和贝那利珠单抗则不能提高ASA耐受性。未来研究将能阐明这一发现。
Nonsteroidal Anti-inflammatory Drug (NSAID) Tolerance After Biological Therapy in Patients With NSAID-Exacerbated Respiratory Disease: A Randomized Comparative Trial
Sánchez J, García E, Lopez JF, Calle A, Buendia JA.
Abstract
BACKGROUND:There are no prospective studies comparing how biological therapies affect nonsteroidal anti-inflammatory drug (NSAID) tolerance in NSAID-exacerbated respiratory disease.
OBJECTIVE:To study the induction of NSAID tolerance after biological therapy in patients with NSAID-exacerbated respiratory disease.
METHODS:A prospective pilot study in a real-world clinic setting was conducted among subjects with severe asthma and type 2 inflammation. A random allocation of therapy was carried out: benralizumab, dupilumab, mepolizumab, or omalizumab. NSAID intolerance was confirmed by an oral challenge test (OCT) using acetyl-salicylic acid (ASA-OCT). The principal outcome was NSAID tolerance according to OCT before and after 6 months of each biological therapy (intragroup comparisons). As exploratory outcomes, we compared NSAID tolerance between biological therapies (intergroup comparisons).
RESULTS:A total of 38 subjects were included; 9 received benralizumab, 10 dupilumab, 9 mepolizumab, and 10 omalizumab. There was an increase in the concentration needed to produce a reaction during ASA-OCT with omalizumab (P < .001) and dupilumab (P = .004) but not with mepolizumab and benralizumab. Omalizumab and dupilumab achieved the highest frequency of NSAID tolerance (omalizumab 60%, dupilumab 40%, mepolizumab 22%, and benralizumab 22%).
CONCLUSIONS:Biological therapies for asthma are useful for inducing NSAID tolerance; however, in patients with type 2 inflammation and high levels of total IgE, atopy, and eosinophils, anti-IgE or anti-IL4/13 seem to be more effective than antieosinophilic therapies. Omalizumab and dupilumab increased ASA tolerance, whereas mepolizumab and benralizumab did not. Future trials will be able to clarify this finding.
背景：目前尚无前瞻性研究比较生物治疗如何影响非甾体抗炎药（NSAID）诱导呼吸道疾病中的NSAID耐受性。
目的：本研究旨在研究生物治疗如何诱导NSAID诱导呼吸道疾病患者的NSAID耐受性。
方法：本研究在现实世界的临床环境中，对罹患重症哮喘和2型炎症的受试者进行前瞻性试点研究。随机分配治疗方案：贝那利珠单抗、度普利尤单抗、美泊利珠单抗或奥马珠单抗 。通过乙酰水杨酸（ASA-OCT）口服激发试验（OCT）证实NSAID不耐受。主要结果是在每次6个月生物治疗前后基于OCT的NSAID耐受性（组内比较）。作为探索性结果，本研究比较了生物治疗之间的NSAID耐受性（组间比较）。
结果：本研究共纳入38名受试者，其中9人接受贝那利珠单抗、10人接受度普利尤单抗、9人接受美泊利珠单抗和10人接受奥马珠单抗治疗。在ASA-OCT中，奥马珠单抗（P<.001）和度普利尤单抗（P=.004）组产生反应所需的浓度增加，但美泊利珠单抗和贝那利珠单抗无增加。奥马珠单抗和度普利尤单抗获得NSAID耐受的频率最高（奥马珠单抗60%，度普利尤单抗40%，美泊利珠单抗22%，贝那利珠单抗22%）。
结论：哮喘的生物治疗有助于诱导NSAID耐受。然而在2型炎症和总IgE、特应性和嗜酸性粒细胞水平高的患者中，抗IgE或抗IL4/13似乎比抗嗜酸性粒细胞治疗更有效。奥马珠单抗和度普利尤单抗可提高ASA耐受性，而美泊利珠单抗和贝那利珠单抗则不能提高ASA耐受性。未来研究将能阐明这一发现。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(J Allergy Clin Immunol Pract. 2023 Jul;11(7):2172-2179. doi: 10.1016/j.jaip.2023.04.033.)
(J Allergy Clin Immunol Pract. 2023 Jul;11(7):2172-2179. doi: 10.1016/j.jaip.2023.04.033.)
Nonsteroidal Anti-inflammatory Drug (NSAID) Tolerance After Biological Therapy in Patients With NSAID-Exacerbated Respiratory Disease: A Randomized Comparative Trial
Sánchez J, García E, Lopez JF, Calle A, Buendia JA.
Abstract
BACKGROUND:There are no prospective studies comparing how biological therapies affect nonsteroidal anti-inflammatory drug (NSAID) tolerance in NSAID-exacerbated respiratory disease.
OBJECTIVE:To study the induction of NSAID tolerance after biological therapy in patients with NSAID-exacerbated respiratory disease.
METHODS:A prospective pilot study in a real-world clinic setting was conducted among subjects with severe asthma and type 2 inflammation. A random allocation of therapy was carried out: benralizumab, dupilumab, mepolizumab, or omalizumab. NSAID intolerance was confirmed by an oral challenge test (OCT) using acetyl-salicylic acid (ASA-OCT). The principal outcome was NSAID tolerance according to OCT before and after 6 months of each biological therapy (intragroup comparisons). As exploratory outcomes, we compared NSAID tolerance between biological therapies (intergroup comparisons).
RESULTS:A total of 38 subjects were included; 9 received benralizumab, 10 dupilumab, 9 mepolizumab, and 10 omalizumab. There was an increase in the concentration needed to produce a reaction during ASA-OCT with omalizumab (P < .001) and dupilumab (P = .004) but not with mepolizumab and benralizumab. Omalizumab and dupilumab achieved the highest frequency of NSAID tolerance (omalizumab 60%, dupilumab 40%, mepolizumab 22%, and benralizumab 22%).
CONCLUSIONS:Biological therapies for asthma are useful for inducing NSAID tolerance; however, in patients with type 2 inflammation and high levels of total IgE, atopy, and eosinophils, anti-IgE or anti-IL4/13 seem to be more effective than antieosinophilic therapies. Omalizumab and dupilumab increased ASA tolerance, whereas mepolizumab and benralizumab did not. Future trials will be able to clarify this finding.
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