背景:Nucala有效性研究(NEST)评估了美泊利单抗在以前在真实世界研究中代表性不足的国家中对重度哮喘(SA)患者的有效性。
方法:多国,双向,自我控制,在哥伦比亚进行的观察性队列研究,智利,印度,蒂尔基耶,沙特阿拉伯,阿拉伯联合酋长国,科威特,阿曼,卡塔尔。来自SA患者的历史和/或前瞻性数据在mepolizumab开始前和后12个月进行评估。
方法:临床显著加重(CSE)的发生率比(IRR)。关键次要终点:医疗保健资源利用率(HCRU),口服皮质类固醇(OCS)使用,肺功能和症状控制(哮喘控制测试[ACT]评分)。
结果:总体而言,525例SA负荷开始前(几何平均血液嗜酸性粒细胞计数[BEC]490.7个细胞/μl;31.4%的生物使用;37.3%的肥胖)接受至少一个剂量的美泊利单抗100mg皮下。启动后,观察到CSE显著减少(76%[p<0.001];IRR[95%置信区间]0.24[0.19-0.30]);72.0%的患者没有CSE.Mepolizumab治疗导致OCS使用减少(启动前52.8%与开始后16.6%)和OCS剂量的平均值(标准偏差[SD])变化为-18.1(20.7)mg开始后;36.1%的患者无OCS。开始后住院的患者较少(22.5%的开始前与启动后6.9%)。1s内平均用力呼气量(SD)的改善(启动前62.8[20.2]%与启动后73.0[22.7]%)和ACT得分(启动前15.0%与64.5%的患者在哮喘控制良好后开始治疗)。BEC≥500个细胞/μl的患者比例从起始前的84.4%下降到起始后的18.1%。
结论:Mepolizumab通过显着降低CSE来有效降低SA的负担,减少OCS使用和HCCU,改善肺功能和哮喘控制,这可以转化为在所研究的国家中改善SA和高度OCS依赖患者的健康相关生活质量。本文提供了图形摘要。
尽管经过优化治疗,但当哮喘症状仍未得到控制时,就会发生严重哮喘。在许多中低收入国家,在中东的一些国家,亚洲,拉丁美洲和阿拉伯湾,严重哮喘患者的管理和治疗仍然很差,许多患者有计划外的医院就诊或入院,长期使用类固醇.Mepolizumab是一种可注射的单克隆抗体,被批准为≥6岁患者的严重哮喘的附加治疗。在临床试验中,mepolizumab已证明可降低临床上显著加重(CSE;需要全身性皮质类固醇和/或急诊室就诊和/或住院的哮喘加重)的风险,并可通过减少由嗜酸性粒细胞(一种白细胞)产生引起的炎症来降低重度哮喘患者口服皮质类固醇(OCS)治疗的需要。进行了Nucala有效性研究(NEST),以观察mepolizumab在哥伦比亚严重哮喘患者中的有效性。智利,印度,土耳其,沙特阿拉伯,阿拉伯联合酋长国,科威特,阿曼和卡塔尔。在mepolizumab开始前和开始后12个月比较CSE和其他结果的频率。启动后,CSE的风险显着降低了76%(p<0.001),72%的患者没有CSE。依赖OCS的患者越少,36.1%的患者根本不使用OCS,住院患者较少。肺功能和哮喘控制也得到改善。NEST表明,美泊利单抗可以使生活在疾病相关负担和OCS使用仍然很高的国家的重度哮喘患者受益。
BACKGROUND: The Nucala Effectiveness Study (NEST) assessed the effectiveness of
mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies.
METHODS: A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-
mepolizumab initiation.
METHODS: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores).
RESULTS: Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs.
Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of - 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation.
CONCLUSIONS: Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.
Severe asthma occurs when asthma symptoms remain uncontrolled despite optimised treatment. In many low-middle income countries, and in some countries in the Middle East, Asia, Latin America and the Arab Gulf, the management and treatment of patients with severe asthma remain poor, with many patients having unscheduled hospital visits or admission, and use of steroids for a prolonged period.
Mepolizumab is an injectable monoclonal antibody approved as an add-on treatment for severe asthma in patients ≥ 6 years of age. In clinical trials, mepolizumab has demonstrated reductions in the risk of clinically significant exacerbations (CSE; an asthma exacerbation that requires systemic corticosteroids and/or an emergency room visit and/or hospitalisation) and the need for oral corticosteroid (OCS) treatment in patients with severe asthma by reducing inflammation caused by eosinophil (a type of white blood cell) production. The Nucala Effectiveness Study (NEST) was performed to observe the effectiveness of mepolizumab in people with severe asthma in Colombia, Chile, India, Turkey, Saudi Arabia, United Arab Emirates, Kuwait, Oman and Qatar. The frequency of CSEs and other outcomes was compared 12 months pre- and post-
mepolizumab initiation. Post-initiation, the risk of CSEs was significantly reduced by 76% (p < 0.001), and 72% of patients had no CSEs. Fewer patients were dependent on OCS, with 36.1% of patients not using OCS at all, and fewer patients were hospitalised. Lung function and asthma control also improved. NEST shows that mepolizumab could benefit people with severe asthma living in countries where disease-related burden and OCS use remain high.