重度哮喘患者生物疗法的心血管安全性：比利时全国性队列研究
2025/08/31
摘要
背景：在过去几十年里，生物疗法已被批准用于治疗重度过敏性和/或嗜酸性粒细胞性哮喘。有限的研究探讨了生物制剂对（急性）心血管事件的影响，且研究结果相互矛盾。我们旨在研究与未使用生物制剂的患者相比，重度哮喘患者使用抗免疫球蛋白（Ig）-E（奥马珠单抗）和抗白细胞介素（IL）-5/IL - 5受体（IL - 5R）疗法（美泊利珠单抗和贝那利珠单抗）的潜在心血管风险。
方法：在2017年至2022年的比利时全国性数据中确定符合使用生物制剂条件的成年哮喘患者。采用治疗逆概率加权Cox回归分析来研究心血管结局和全因死亡率，同时控制年龄、性别、肥胖、吸烟、合并症、联合用药、病情加重和身体虚弱等因素。
结果：这项队列研究共纳入171,865名患者（平均年龄64岁；55%为女性），其中1826名（1.1%）使用抗Ig - E制剂，2398名（1.4%）使用抗IL - 5/IL - 5R制剂。与未使用生物制剂的患者相比，使用抗Ig - E制剂与显著降低的死亡风险（调整后风险比[aHR] 0.48，95%置信区间[CI] 0.40 - 0.58）、充血性心力衰竭风险（aHR 0.79，95% CI 0.65 - 0.95）、外周动脉疾病风险（aHR 0.66，95% CI 0.51 - 0.86）和中风风险（aHR 0.54，95% CI 0.36 - 0.81）相关。使用抗IL - 5/IL - 5R制剂与显著降低的死亡风险（aHR 0.35，95% CI 0.29 - 0.42）、充血性心力衰竭风险（aHR 0.63，95% CI 0.52 - 0.76）、心律失常风险（aHR 0.78，95% CI 0.68 - 0.90）和外周动脉疾病风险（aHR 0.69，95% CI 0.54 - 0.87）相关。在心肌梗死和肺栓塞风险方面未观察到显著差异。
解读：在这项全国性观察性研究中，与未使用生物制剂的患者相比，重度哮喘患者使用生物疗法与显著降低的全因死亡率和特定心血管疾病风险相关。
Cardiovascular safety of biologic therapies in patients with severe asthma: a nationwide cohort study in Belgium
Frauke Van Vaerenbergh, Delphine Vauterin, Maxim Grymonprez, Lowie E G W Vanfleteren, Guy Brusselle, Lies Lahousse
Abstract
Background: In last decades, biologic therapies have been approved for severe allergic and/or eosinophilic asthma. Limited studies have investigated the effect of biologics on (acute) cardiovascular events, which have reported conflicting results. We aimed to investigate the potential cardiovascular risk of anti-immunoglobulin(Ig)-E (omalizumab) and anti-interleukin(IL)-5/IL5 receptor (IL5R) therapies (mepolizumab and benralizumab) in patients with severe asthma compared with non-biologic users.
Methods: Adult asthma patients eligible for biologics were identified in Belgian nationwide data between 2017 and 2022. Inverse probability of treatment weighted Cox regression was used to investigate cardiovascular outcomes and all-cause mortality, while controlling for age, sex, obesity, smoking, comorbidities, comedication, exacerbations, and frailty.
Findings: This cohort study consisted of 171,865 patients (mean age 64 years; 55% females) including 1826 (1.1%) anti-IgE users and 2398 (1.4%) anti-IL5/IL5R users. Anti-IgE exposure was associated with a significantly lower risk of mortality (aHR 0.48, 95% CI 0.40-0.58), congestive heart failure (aHR 0.79, 95% CI 0.65-0.95), peripheral artery disease (aHR 0.66, 95% CI 0.51-0.86), and stroke (aHR 0.54, 95% CI 0.36-0.81). Anti-IL5/IL5R use was associated with a significantly lower risk of mortality (aHR 0.35, 95% CI 0.29-0.42), congestive heart failure (aHR 0.63, 95% CI 0.52-0.76), arrythmia (aHR 0.78, 95% CI 0.68-0.90), and peripheral artery disease (aHR 0.69, 95% CI 0.54-0.87) compared with non-biologic users. No significant differences in the risk of myocardial infarction and pulmonary embolism were observed.
Interpretation: In this nationwide observational study, biologic therapies for patients with severe asthma were associated with a significantly lower risk of all-cause mortality and specific cardiovascular diseases compared with non-biologic users.
背景：在过去几十年里，生物疗法已被批准用于治疗重度过敏性和/或嗜酸性粒细胞性哮喘。有限的研究探讨了生物制剂对（急性）心血管事件的影响，且研究结果相互矛盾。我们旨在研究与未使用生物制剂的患者相比，重度哮喘患者使用抗免疫球蛋白（Ig）-E（奥马珠单抗）和抗白细胞介素（IL）-5/IL - 5受体（IL - 5R）疗法（美泊利珠单抗和贝那利珠单抗）的潜在心血管风险。
方法：在2017年至2022年的比利时全国性数据中确定符合使用生物制剂条件的成年哮喘患者。采用治疗逆概率加权Cox回归分析来研究心血管结局和全因死亡率，同时控制年龄、性别、肥胖、吸烟、合并症、联合用药、病情加重和身体虚弱等因素。
结果：这项队列研究共纳入171,865名患者（平均年龄64岁；55%为女性），其中1826名（1.1%）使用抗Ig - E制剂，2398名（1.4%）使用抗IL - 5/IL - 5R制剂。与未使用生物制剂的患者相比，使用抗Ig - E制剂与显著降低的死亡风险（调整后风险比[aHR] 0.48，95%置信区间[CI] 0.40 - 0.58）、充血性心力衰竭风险（aHR 0.79，95% CI 0.65 - 0.95）、外周动脉疾病风险（aHR 0.66，95% CI 0.51 - 0.86）和中风风险（aHR 0.54，95% CI 0.36 - 0.81）相关。使用抗IL - 5/IL - 5R制剂与显著降低的死亡风险（aHR 0.35，95% CI 0.29 - 0.42）、充血性心力衰竭风险（aHR 0.63，95% CI 0.52 - 0.76）、心律失常风险（aHR 0.78，95% CI 0.68 - 0.90）和外周动脉疾病风险（aHR 0.69，95% CI 0.54 - 0.87）相关。在心肌梗死和肺栓塞风险方面未观察到显著差异。
解读：在这项全国性观察性研究中，与未使用生物制剂的患者相比，重度哮喘患者使用生物疗法与显著降低的全因死亡率和特定心血管疾病风险相关。
（中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校）
（Lancet Reg Health Eur. 2025 Aug 6:57:101420. doi: 10.1016/j.lanepe.2025.101420. eCollection 2025 Oct.）
Cardiovascular safety of biologic therapies in patients with severe asthma: a nationwide cohort study in Belgium
Frauke Van Vaerenbergh, Delphine Vauterin, Maxim Grymonprez, Lowie E G W Vanfleteren, Guy Brusselle, Lies Lahousse
Abstract
Background: In last decades, biologic therapies have been approved for severe allergic and/or eosinophilic asthma. Limited studies have investigated the effect of biologics on (acute) cardiovascular events, which have reported conflicting results. We aimed to investigate the potential cardiovascular risk of anti-immunoglobulin(Ig)-E (omalizumab) and anti-interleukin(IL)-5/IL5 receptor (IL5R) therapies (mepolizumab and benralizumab) in patients with severe asthma compared with non-biologic users.
Methods: Adult asthma patients eligible for biologics were identified in Belgian nationwide data between 2017 and 2022. Inverse probability of treatment weighted Cox regression was used to investigate cardiovascular outcomes and all-cause mortality, while controlling for age, sex, obesity, smoking, comorbidities, comedication, exacerbations, and frailty.
Findings: This cohort study consisted of 171,865 patients (mean age 64 years; 55% females) including 1826 (1.1%) anti-IgE users and 2398 (1.4%) anti-IL5/IL5R users. Anti-IgE exposure was associated with a significantly lower risk of mortality (aHR 0.48, 95% CI 0.40-0.58), congestive heart failure (aHR 0.79, 95% CI 0.65-0.95), peripheral artery disease (aHR 0.66, 95% CI 0.51-0.86), and stroke (aHR 0.54, 95% CI 0.36-0.81). Anti-IL5/IL5R use was associated with a significantly lower risk of mortality (aHR 0.35, 95% CI 0.29-0.42), congestive heart failure (aHR 0.63, 95% CI 0.52-0.76), arrythmia (aHR 0.78, 95% CI 0.68-0.90), and peripheral artery disease (aHR 0.69, 95% CI 0.54-0.87) compared with non-biologic users. No significant differences in the risk of myocardial infarction and pulmonary embolism were observed.
Interpretation: In this nationwide observational study, biologic therapies for patients with severe asthma were associated with a significantly lower risk of all-cause mortality and specific cardiovascular diseases compared with non-biologic users.
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用于哮喘治疗的孢子启发式吸入给药系统
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