Durán Carlos E, Riera-Arnau Judit, Abtahi Shahab, Pajouheshnia Romin, Hoxhaj Vjola, Gamba Magdalena, Alsina Ema, Martin-Perez Mar, Garcia-Poza Patricia, Llorente-Garcia Ana, Gonzalez-Bermejo Diana, Ibánez Luisa, Sabaté Mònica, Vidal Xavier, Ballarín Elena, Sanfélix-Gimeno Gabriel, Rodríguez-Bernal Clara, Peiró Salvador, García-Sempere Aníbal, Sanchez-Saez Francisco, Ientile Valentina, Ingrasciotta Ylenia, Guarneri Claudio, Tanaglia Matilde, Tari Michele, Herings Ron, Houben Eline, Swart-Polinder Karin, Holthuis Emily, Huerta Consuelo, Gini Rosa, Roberto Giuseppe, Bartolini Claudia, Paoletti Olga, Limoncella Giorgio, Girardi Anna, Hyeraci Giulia, Andersen Morten, Kristiansen Sarah Brøgger, Hallgreen Christine Erikstrup, Klungel Olaf, Sturkenboom Miriam
Julius Center for Health Sciences and Primary Care, Department of Data Science and Biostatistics, University Medical Center Utrecht, Utrecht, Netherlands.
Department of Clinical Pharmacology, Vall Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Front Pharmacol. 2023 Aug 17;14:1207976. doi: 10.3389/fphar.2023.1207976. eCollection 2023.
In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.
2018年3月，作为风险最小化措施（RMM）的一部分，欧洲口服维甲酸类药物的妊娠预防计划进行了更新，强调其在孕妇中的禁忌。通过评估异维A酸、阿利维A酸和阿维A的使用模式、避孕措施、妊娠试验、停药情况以及与维甲酸类药物处方同时发生的妊娠情况，来衡量2018年欧洲RMM修订的影响。对2010年1月至2020年12月来自丹麦、荷兰、西班牙和意大利四个国家六个电子健康数据源的育龄女性（12 - 55岁）队列进行中断时间序列（ITS）分析，以比较风险最小化措施实施后的水平和趋势变化。计算了2018年RMM前后口服维甲酸类药物的每月使用数据（发病率[IR]、患病率[PR]和比例），以及停药率、避孕覆盖率、妊娠试验和口服维甲酸类药物暴露妊娠率。在10,714,182名育龄女性中，88,992人在研究期间的任何时间使用过口服维甲酸类药物（平均年龄18.9 - 22.2岁）。我们发现2018年RMM后育龄女性维甲酸类药物使用的发病率或患病率没有显著的水平和趋势变化。超过95%的病例停药原因不明。西班牙的避孕措施使用呈显著上升趋势；其他数据库的此类信息有限。妊娠试验记录很少，因此无法进行ITS分析建模。2018年RMM后，维甲酸类药物使用期间的妊娠发生率以及妊娠期间开始使用维甲酸类药物的比例分别在0.0至0.4和0.2至0.8之间。这项研究表明，2018年RMM对四个欧洲国家育龄女性口服维甲酸类药物使用模式的影响有限。维甲酸类药物使用期间仍会发生妊娠，并且仍会给孕妇开具口服维甲酸类药物。大多数数据库中的避孕和妊娠试验信息有限。监管机构、政策制定者、开处方者和研究人员必须重新思考实施策略，以避免任何妊娠与维甲酸类药物使用暂时相关。
