用生物制剂治疗哮喘患者心血管和其他系统不良后果的预防

IF 19.4 1区医学 Q1 CRITICAL CARE MEDICINE

American journal of respiratory and critical care medicine Pub Date : 2025-07-01 DOI:10.1164/rccm.202501-0246OC

Mohsen Sadatsafavi, Trung N Tran, Ghislaine Scelo, Ming-Ju Tsai, John Busby, Benjamin Emmanuel, Liam G Heaney, Christine Jenkins, Flavia Hoyte, Giorgio Walter Canonica, Rohit Katial, Enrico Heffler, Eileen Wang, Francesca Puggioni, Michael E Wechsler, Ledit R F Ardusso, Jorge Máspero, Martin Sivori, Cathy Emmas, Andrew N Menzies-Gow, Neda Stjepanovic, Sinthia Z Bosnic-Anticevich, Belinda Cochrane, Eve Denton, Peter G Gibson, Mark Hew, Peter G Middleton, Matthew J Peters, Guy G Brusselle, Renaud Louis, Florence Schleich, George C Christoff, Todor A Popov, Celine Bergeron, Mohit Bhutani, Kenneth R Chapman, Andréanne Côté, Simon Couillard, Delbert R Dorscheid, Libardo Jiménez-Maldonado, Ivan Solarte, Carlos A Torres-Duque, Susanne Hansen, Celeste M Porsbjerg, Charlotte Suppli Ulrik, Alan Altraja, Arnaud Bourdin, Konstantinos P Exarchos, Athena Gogali, Konstantinos Kostikas, Michael P Makris, Andriana I Papaioannou, Patrick D Mitchell, Takashi Iwanaga, Tatsuya Nagano, Yuji Tohda, Mona S Al-Ahmad, Désirée Larenas-Linnemann, Bernt Bøgvald Aarli, Piotr Kuna, Cláudia Chaves Loureiro, Riyad Al-Lehebi, Adeeb A Bulkhi, Wenjia Chen, Yah Ru Juang, Mariko Siyue Koh, Anqi Liu, Chin Kook Rhee, Borja G Cosio, Luis Perez-de-Llano, Diahn-Warng Perng, Chau-Chyun Sheu, Hao-Chien Wang, Bassam Mahboub, Laila Salameh, David J Jackson, Pujan H Patel, Paul E Pfeffer, Njira Lugogo, Roy Alton Pleasants, Aaron Beastall, Lakmini Bulathsinhala, Victoria Carter, Nevaashni Eleangovan, Kirsty Fletton, John Townend, Ruth B Murray, David B Price

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引用次数: 0

摘要

理由：尽管临床试验已经证明口服皮质类固醇（OCS）生物制剂对严重哮喘患者的节约作用，但这是否意味着减少新发的OCS相关不良后果尚不清楚。目的：比较生物启动者和非生物启动者发生新发ocs相关不良结局的风险。方法：这是一项纵向队列研究，使用来自国际严重哮喘登记处(ISAR；16个国家)和最佳患者护理研究数据库(OPCRD；英国)。对于生物启动物，索引日期为生物启动日期。对于非发起者，它是注册日期（ISAR）或随机医疗预约日期（OPCRD）。使用治疗加权逆概率来提高组间的可比性，并使用加权Cox比例风险模型来估计自指数日期起5年内发生ocs相关不良结局的风险比（HR）。测量和主要结果：纳入42908例患者。总体而言，27.3%和4.7%的生物启动剂和非启动剂是长期OCS使用者（指数前一年每日摄入量≥连续90天），平均泼尼松龙当量日剂量分别为10.2 mg和6.2 mg。与非启动剂相比，生物启动剂发生任何与ocs相关的不良后果的几率降低(HR [95% CI]: 0.82 [0.72-0.93]；P =0.002)，主要是由于糖尿病发病率降低(0.62 [0.45-0.87]；P =0.006])，主要心血管事件(0.65 [0.44-0.97]；P =0.034)，焦虑/抑郁(0.68 [0.55-0.85]；p = 0.001)。在新发白内障（HR: 0.77 [95% CI: 0.47-1.25]）、睡眠呼吸暂停（HR: 0.82 [95% CI: 0.78-1.41]）或其他与ocs相关的不良反应（如骨质疏松症）的评估率方面，两组无显著差异。两个数据集的结果是一致的。结论：我们的研究结果强调了生物制剂在预防重度哮喘患者新发ocs相关不良结局中的作用。

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Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics.

Rationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

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来源期刊

American journal of respiratory and critical care medicine 医学-呼吸系统

CiteScore

27.30

自引率

4.50%

发文量

1313

审稿时长

3-6 weeks

期刊介绍： The American Journal of Respiratory and Critical Care Medicine focuses on human biology and disease, as well as animal studies that contribute to the understanding of pathophysiology and treatment of diseases that affect the respiratory system and critically ill patients. Papers that are solely or predominantly based in cell and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The Journal also seeks to publish clinical trials and outstanding review articles on areas of interest in several forms. The State-of-the-Art review is a treatise usually covering a broad field that brings bench research to the bedside. Shorter reviews are published as Critical Care Perspectives or Pulmonary Perspectives. These are generally focused on a more limited area and advance a concerted opinion about care for a specific process. Concise Clinical Reviews provide an evidence-based synthesis of the literature pertaining to topics of fundamental importance to the practice of pulmonary, critical care, and sleep medicine. Images providing advances or unusual contributions to the field are published as Images in Pulmonary, Critical Care, Sleep Medicine and the Sciences. A recent trend and future direction of the Journal has been to include debates of a topical nature on issues of importance in pulmonary and critical care medicine and to the membership of the American Thoracic Society. Other recent changes have included encompassing works from the field of critical care medicine and the extension of the editorial governing of journal policy to colleagues outside of the United States of America. The focus and direction of the Journal is to establish an international forum for state-of-the-art respiratory and critical care medicine.