Richards Levi B, van Bragt Job J M H, Aarab Reim, Longo Cristina, Neerincx Anne H, Sont Jaap K, Weersink Els J M, Braunstahl Gert-Jan, Brinke Anneke Ten, Bel Elisabeth H D, Maitland-van der Zee Anke-Hilse
Department of Respiratory Medicine, Amsterdam University Medical Centres, (Amsterdam UMC), University of Amsterdam, Amsterdam, the Netherlands.
Department of Respiratory Medicine, Amsterdam University Medical Centres, (Amsterdam UMC), University of Amsterdam, Amsterdam, the Netherlands.
J Allergy Clin Immunol Pract. 2020 Oct;8(9):2999-3008.e1. doi: 10.1016/j.jaip.2020.04.029. Epub 2020 Apr 25.
Patients with severe asthma not meeting the strict trial eligibility criteria for mepolizumab are now routinely treated with this biological in clinical practice, but it remains unclear whether these ineligible patients respond differently to mepolizumab treatment.
This study investigated the extent and reasons for trial ineligibility of real-life, mepolizumab-treated patients with severe asthma and compared the characteristics of these patients with trial populations. Subsequently, therapeutic response in ineligible patients was assessed on the basis of oral corticosteroid (OCS) reduction.
Trial eligibility, population differences, and therapeutic response were assessed using the baseline characteristics of mepolizumab-receiving patients with severe asthma treated in the Amsterdam University Medical Centres and OCS dose at 6 months for OCS-dependent patients extracted from patients' electronic health records. Eligibility criteria and population characteristics from trials investigating mepolizumab were extracted from their original publications.
A total of 82.4% of 119 mepolizumab-receiving, real-life patients with severe asthma were ineligible for trial inclusion, wherein 42.9% and 39.5% were excluded on the basis of inclusion and exclusion criteria, respectively. The clinical care population was older, more often male and demonstrating a better lung function under lower OCS maintenance dosages in comparison with trial populations. A total of 50% of 66 ineligible, OCS-dependent mepolizumab-treated patients were able to reduce their maintenance OCS dosage to ≤5 mg prednisone/day.
A large proportion of the real-life, mepolizumab-treated population with severe asthma would be excluded from trial participation, and significant differences in population characteristics exist. Regardless, a large fraction of ineligible patients in clinical care can reduce maintenance OCS dosage under mepolizumab therapy.
在临床实践中，不符合美泊利珠单抗严格试验纳入标准的重度哮喘患者现在常规接受这种生物制剂治疗，但这些不符合标准的患者对美泊利珠单抗治疗的反应是否不同仍不清楚。
本研究调查了现实生活中接受美泊利珠单抗治疗的重度哮喘患者不符合试验纳入标准的程度及原因，并将这些患者的特征与试验人群进行比较。随后，根据口服糖皮质激素（OCS）减量情况评估不符合标准患者的治疗反应。
利用阿姆斯特丹大学医学中心接受美泊利珠单抗治疗的重度哮喘患者的基线特征以及从患者电子健康记录中提取的OCS依赖患者6个月时的OCS剂量，评估试验纳入标准、人群差异和治疗反应。从美泊利珠单抗相关试验的原始出版物中提取纳入标准和人群特征。
119例接受美泊利珠单抗治疗的现实生活中的重度哮喘患者中，共有82.4%不符合试验纳入标准，其中分别有42.9%和39.5%是基于纳入标准和排除标准被排除。与试验人群相比，临床护理人群年龄更大，男性更多，且在较低的OCS维持剂量下肺功能更好。66例接受美泊利珠单抗治疗且OCS依赖的不符合标准患者中，共有50%能够将其维持OCS剂量减至≤5mg泼尼松/天。
现实生活中接受美泊利珠单抗治疗的重度哮喘患者中有很大一部分将被排除在试验之外，且人群特征存在显著差异。尽管如此，临床护理中很大一部分不符合标准的患者在美泊利珠单抗治疗下能够减少维持OCS剂量。
