Kang Sang Oh, Min Kyung Hyun, Kim Hyun Jeong, Kim Tae Hyeok, Kim Woorim, Lee Kyung Eun
College of Pharmacy, Chungbuk National University, 660-1 Yeonje-ri, Osong-eup, Heungdeok-gu, Cheongju-si, 28160, Republic of Korea.
Asthma Res Pract. 2021 Mar 17;7(1):4. doi: 10.1186/s40733-021-00070-4.
In March 2020, the US Food and Drug Administration decided that the dangers related to neuropsychiatric events (NPEs) of montelukast, one of the leukotriene modifying agents (LTMAs), should be communicated through 'boxed warning'. In case of NPEs, the prevalence has been the highest in elderly people. Because the characteristics of the elderly such as old age itself can act as risk factors. Therefore, an investigation on safety of LTMAs related to NPEs in elderly using LTMAs is needed.
A nested case-control study using an elderly sample cohort from the Korean National Health Insurance Service database was used. The asthma cohort included asthma patients newly diagnosed between 2003 and 2013. Within the asthma cohort, the case group was defined as patients who were diagnosed with NPEs. Among patients who had never been diagnosed with NPEs, the control group was selected by matching 1:1 by propensity score. Patients who were prescribed LTMAs for 1 year prior to index date were defined as the exposure group. The logistic regression model was used to measure the effect of LTMAs on NPEs.
We identified 141,165 patients with newly diagnosed asthma, and selected 31,992 patients per each case and control group. Exposure to LTMAs significantly increased the risk of overall NPEs about in comparison with the absence of exposure (crude odds ratio [OR] 1.58, 95% CI 1.50-1.68). After adjusting for confounding factors, the overall NPEs risk increased (adjusted OR, 1.67, 95% CI 1.58-1.78).
This study suggests that elderly asthma patients prescribed LTMAs had a higher risk of NPEs than patients who were not treated with LTMAs. Therefore, clinicians should be aware of the potential risks of LTMAs.
2020年3月，美国食品药品监督管理局决定，白三烯调节剂（LTMAs）之一的孟鲁司特与神经精神事件（NPEs）相关的危险应通过“黑框警告”进行告知。在发生NPEs的情况下，老年人中的患病率最高。因为老年人自身的衰老等特征可能成为危险因素。因此，有必要对使用LTMAs的老年人中与NPEs相关的LTMAs安全性进行调查。
采用一项巢式病例对照研究，使用来自韩国国民健康保险服务数据库的老年样本队列。哮喘队列包括2003年至2013年新诊断的哮喘患者。在哮喘队列中，病例组定义为被诊断为NPEs的患者。在从未被诊断为NPEs的患者中，通过倾向评分1:1匹配选择对照组。在索引日期前接受LTMAs治疗1年的患者被定义为暴露组。采用逻辑回归模型来衡量LTMAs对NPEs的影响。
我们确定了141165例新诊断哮喘患者，并在每个病例组和对照组中各选择了31992例患者。与未暴露相比，暴露于LTMAs显著增加了总体NPEs的风险（粗比值比[OR]为1.58，95%可信区间为1.50 - 1.68）。在调整混杂因素后，总体NPEs风险增加（调整后OR为1.67，95%可信区间为1.58 - 1.78）。
本研究表明，使用LTMAs的老年哮喘患者发生NPEs的风险高于未接受LTMAs治疗的患者。因此，临床医生应意识到LTMAs的潜在风险。
