INTRODUCTION In May 2013 and March 2014, the European Medicines Agency (EMA) issued two decisions restricting the use of strontium ranelate (SR). These risk minimisation measures (RMM) introduced new contraindications and limited the indications of SR therapy. The EMA required an assessment of the impact of RMMs on the use of SR in Europe. Methods design: multi-national, multi-database cohort Setting: electronic medical record databases based on hospital (Denmark) and primary care provenance (Italy, Spain, the Netherlands, UK). PARTICIPANTS the database source populations were included for population-based analyses, and SR users for patient-level analyses. INTERVENTION New RMMs included contraindications (ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension) and restricted SR indication to severe osteoporosis with initiation by experienced physician and not as first line anti-osteoporosis therapy. METHODS Prevalence and incidence rates of SR use in the population; prevalence of contraindications and restricted indications in SR users, plus 1-year therapy persistence. Drug use measures were calculated in three periods for comparison: reference (2004 to May 2013), transition (June 2013 to March 2014) and assessment (from April 2014 to end 2016). RESULTS The study population included 143 million person-years(PY) of follow-up and 76,141 incident episodes of SR treatment. Average monthly prevalence rates of SR use dropped by 86.4% from 62.6/10,000 PY (95 CI 62.4-62.9) in the reference to 8.5 (8.5-8.6) in the assessment period. Similarly, the incidence rate of SR use fell by 97.3% from 7.4/10,000 PY (7.4-7.4) to 0.2 (0.2-0.2) between the reference and assessment period. The prevalence of any contraindication decreased, whilst the prevalence of restricted indications increased in these periods. One-year persistence decreased in the assessment compared with reference period. CONCLUSIONS Our study demonstrates a substantial impact of the regulatory action to restrict use of SR in Europe: SR utilisation overall decreased strongly. The proportion of patients fulfilling the restricted indications, without contraindications, increased after the proposed RMMs.

中文翻译：

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风险最小化措施对欧洲雷奈酸锶使用的影响：EU-ADR联盟在5个欧盟国家进行的多国队列研究。

简介2013年5月和2014年3月，欧洲药品管理局（EMA）发布了两项限制使用雷奈酸锶（SR）的决定。这些风险最小化措施（RMM）引入了新的禁忌症，并限制了SR治疗的适应症。EMA要求评估RMM在欧洲对SR使用的影响。方法设计：跨国，多数据库队列设置：基于医院（丹麦）和基层医疗出处（意大利，西班牙，荷兰，英国）的电子病历数据库。参与者包括数据库源人群以进行基于人群的分析，并包括SR用户以进行患者水平的分析。干预措施新的RMM包括禁忌症（缺血性心脏病，外周动脉疾病，脑血管疾病，不受控制的高血压）和严重的骨质疏松症的SR适应症应由经验丰富的医师开始，而不是作为一线抗骨质疏松症治疗。方法人群中SR使用的流行率和发生率；SR使用者禁忌症和禁忌症的患病率，以及1年的治疗持续时间。分三个阶段计算了药物使用措施以进行比较：参考（2004年至2013年5月），过渡（2013年6月至2014年3月）和评估（从2014年4月至2016年底）。结果研究人群包括1.43亿人年（PY）的随访和76,141例SR治疗事件。SR使用的平均每月患病率从评估期的6.5（8.5-8.6）的参考值62.6 / 10,000 PY（95 CI 62.4-62.9）下降了86.4％。同样，SR使用的发生率下降了97。参考期和评估期之间的百分比从7.4 / 10,000 PY（7.4-7.4）到0.2（0.2-0.2）为3％。在这些时期，禁忌症的患病率下降，而限制性禁忌症的患病率上升。与参考期相比，评估中的一年持续性降低了。结论我们的研究表明，欧洲限制使用SR的监管措施产生了重大影响：SR利用率总体上大幅下降。提议的RMM后，符合严格适应症且无禁忌症的患者比例有所增加。与参考期相比，评估中的一年持续性降低了。结论我们的研究表明，欧洲限制使用SR的监管措施产生了重大影响：SR利用率总体上大幅下降。提议的RMM后，符合严格适应症且无禁忌症的患者比例有所增加。与参考期相比，评估中的一年持续性降低了。结论我们的研究表明，欧洲限制使用SR的监管措施产生了重大影响：SR利用率总体上大幅下降。提议的RMM后，符合严格适应症且无禁忌症的患者比例有所增加。