Relieving gastrointestinal symptoms is a research priority in cystic fibrosis. Emerging evidence highlights effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on gastrointestinal function, including pancreatic sufficiency. This study explores ivacaftor licensing and treatment on recorded pancreatic enzyme replacement therapy (PERT) prescription in the US and UK CF registries. Retrospective longitudinal registry study of recorded pancreatic PERT use between 2008 and 2017. Interrupted time series analysis in propensity-matched cohorts estimated annual change and step change according to ivacaftor eligibility before and after licensing year, 2012. Generalised estimating equations assessed adjusted risk of PERT use in individuals treated with ivacaftor after 2012 compared to untreated individuals. In the US CF registry, the difference in annual change in prevalence of PERT use post-2012 between eligible cases and ineligible controls was -5.0 per 1000 people/year (95 %CI -7.6; -2.3, = 0.001). The step change and annual change in prevalence of PERT use in eligible cases was not significantly different to controls in the UK CF registry. Relative to the relationship in 2013, ivacaftor treatment in the US CF registry was associated with a lower adjusted risk ratio of PERT use compared to untreated individuals by 2016 (0.97, 95 %CI 0.96; 0.99), which was not observed in the UK CF registry. Licensing of ivacaftor was followed by a lower prevalence of PERT use in the eligible US population compared to pre-licensing period, as well as lower risk of PERT use in those who received treatment. Inconsistencies in US and UK CF registries were observed.

中文翻译：

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ivacaftor 许可后的胰酶处方：美国和英国囊性纤维化登记处的回顾性分析

缓解胃肠道症状是囊性纤维化的研究重点。新的证据强调了囊性纤维化跨膜电导调节剂（CFTR）调节剂对胃肠道功能（包括胰腺功能充足）的影响。本研究探讨了 ivacaftor 在美国和英国 CF 登记处记录的胰酶替代疗法 (PERT) 处方的许可和治疗。对 2008 年至 2017 年间记录的胰腺 PERT 使用进行的回顾性纵向登记研究。倾向匹配队列中的中断时间序列分析根据 ivacaftor 资格在 2012 年许可之前和之后估计年度变化和阶跃变化。广义估计方程评估了 PERT 使用的调整风险2012 年之后接受 ivacaftor 治疗的个体与未治疗的个体相比。在美国 CF 登记中，2012 年后合格病例和不合格对照之间 PERT 使用流行率的年度变化差异为每 1000 人 -5.0 人/年 (95%CI -7.6; -2.3, = 0.001)。符合条件的病例中 PERT 使用率的阶跃变化和年度变化与英国 CF 登记处的对照没有显着差异。相对于 2013 年的关系，到 2016 年，美国 CF 登记处的 ivacaftor 治疗与未治疗个体相比，PERT 使用的调整后风险比较低相关（0.97，95 % CI 0.96；0.99），而在英国 CF 中未观察到这一点注册表。与许可前相比，ivacaftor 获得许可后，符合条件的美国人群中 PERT 使用的流行率较低，接受治疗的人群中 PERT 使用的风险也较低。我们观察到美国和英国 CF 登记处存在不一致的情况。