School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, Korea.
Yonsei Med J. 2024 Feb;65(2):120-128. doi: 10.3349/ymj.2023.0207.
Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile.
We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol.
We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47).
In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.
由于安全问题，丙帕他莫在欧洲被撤市，韩国监管机构要求开展一项上市后监测研究，以调查其安全性概况。
我们使用韩国的索赔数据库，对 2010 年至 2019 年期间发生的包括过敏反应、血栓形成和史蒂文斯-约翰逊综合征（SJS）在内的感兴趣结局的病例和对照进行了嵌套病例对照和病例时间对照（CTC）分析。风险集抽样用于根据年龄、性别、队列入组日期和随访时间，为每个病例匹配最多 10 个对照。过敏反应、血栓形成和 SJS 的暴露情况分别在指数日期的 7、90 和 30 天内进行评估。我们使用条件逻辑回归计算比值比（OR）及其 95%置信区间（CI），以评估与丙帕他莫相关的结局风险。
我们共确定了过敏反应（n=61）、血栓形成（n=95）和 SJS（n=1）病例，并将其与对照组（173、268 和 4 例）进行了匹配。在嵌套病例对照分析中，由于风险期内丙帕他莫使用者数量较少，过敏反应和 SJS 的 OR 无法估计；而血栓形成的 OR 为 1.60（95%CI 0.71-3.62）。在 CTC 设计中，仅对血栓形成进行了效果估计（OR 0.56，95%CI 0.09-3.47）。
在嵌套病例对照和 CTC 分析中，丙帕他莫与过敏反应、血栓形成或 SJS 的风险增加无关。这项研究使用了常规收集的临床数据，为丙帕他莫在全国范围内人群中的安全性提供了令人安心的真实世界证据，支持了监管决策。
