Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Data Science, Section of Clinical Epidemiology, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
PLoS One. 2024 Jun 11;19(6):e0305320. doi: 10.1371/journal.pone.0305320. eCollection 2024.
Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age.
A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users.
Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users.
Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.
在日本，雷贝拉唑已与非甾体抗炎药（NSAIDs）联合使用了几十年。本研究旨在评估雷贝拉唑在预防除年龄以外无 NSAIDs 诱导性溃疡危险因素的新 NSAIDs 使用者发生上消化道出血的有效性。
本研究使用了参与日本长寿改善和公平证据研究的 17 个市 166 万居民的医疗报销数据，采用巢式病例对照研究。队列入组（t0）对应新诊断为骨关节炎或腰痛的 NSAIDs 使用者。排除年龄以外有 NSAIDs 诱导性溃疡危险因素的患者。病例定义为因上消化道出血接受胃镜检查的患者（发生日期定义为索引日期）。每个病例的索引日期，通过性别、年龄、随访时间、NSAIDs 的类型和剂量匹配，最多选择 10 名非病例作为对照。雷贝拉唑的暴露定义为 t0 至索引日期的处方状态：非使用者（在随访期间未同时开具雷贝拉唑）、连续使用者（从 t0 开始与 NSAIDs 同时开具相同数量的片剂）和不规则使用者（既非非使用者也非连续使用者）。采用条件 logistic 回归分析估计与非使用者相比，每个类别的比值比。
在符合纳入标准的 67561 名患者中，选择了 215 例病例和 1516 例对照。与非使用者相比，连续使用者的比值比及其 95%置信区间为 0.65（0.44-0.96），不规则使用者为 2.57（1.73-3.81）。
在亚洲新诊断为骨关节炎或腰痛的 NSAIDs 使用者队列中，连续联合使用雷贝拉唑可显著降低上消化道出血风险，且这些患者除年龄以外无其他危险因素。
