PDF(Pubmed)
Abstract：
Background: Elexacaftor-tezacaftor-ivacaftor (ETI) is a novel, highly effective CFTR modulator combination proven to enhance lung function and body weight in people with cystic fibrosis (pwCF) carrying a F508del mutation. Recently, we revealed significant reductions in abdominal symptoms (AS) in German, British, and Irish pwCF after 24-26 weeks of ETI using the CFAbd-Score, the first patient-reported outcome measure (PROM) specifically developed and validated for pwCF following FDA guidelines. Notably, many pwCF reported marked changes in their AS during the first days of the new treatment. To capture these immediate effects, we developed the CFAbd-day2day, a CF-specific GI-diary, following FDA and COSMIN guidelines. Aim: To prospectively capture the immediate dynamics of AS using the CFAbd-day2day 14 days before and 14-28 days after ETI initiation. In addition, we aim to provide validation steps of the novel PROM concerning sensitivity to changes. Methods: To develop the CFAbd-day2day, focus groups (community voice = pwCF and their proxies and CF specialists from different fields) were repeatedly consulted. Before and during the new ETI therapy, pwCF prospectively scored AS on a daily basis with the CFAbd-day2day. Results: Altogether, 45 pwCF attended in five CF centers prospectively completed the CFAbd-day2day before (mean ± sd:14 ± 7 days) and after (mean ± sd: 28 ± 23 days) ETI initiation. On the one hand, cumulative scores significantly decreased during the 3-4-week time frame after ETI initiation, compared to 2 weeks prior to therapy. On the other hand, many patients who revealed a relatively stable level of AS before ETI reported changes during the first days of treatment with the highly effective CFTR modulators. Factors like pain and flatulence increased in up to 21% of patients during the first 14 days of therapy, but they improved during days 15-27. Conclusion: The CFAbd-day2day, specifically developed and in the process of validation to prospectively capture GI symptoms in pwCF, provides new substantial insights into the dynamics of AS in pwCF receiving a new treatment with ETI. This novel tool is also helpful in prospectively monitoring patients with specific GI problems. International implementation and further validation steps of the diary are ongoing.
摘要：
背景：Elexacaftor-tezacaftor-ivacaftor（ETI）是一部小说，高效的CFTR调节剂组合被证明可以增强患有F508del突变的囊性纤维化（pwCF）患者的肺功能和体重。最近,我们发现德国人的腹部症状（AS）显着减少，英国,和爱尔兰pwCF后24-26周的ETI使用CFAbd评分，第一个患者报告的结局指标(PROM)是根据FDA指南专门为pwCF开发和验证的.值得注意的是,许多pwCF报告在新治疗的第一天AS发生了明显变化.为了捕捉这些直接影响，我们开发了CFAbd-day2day,CF特定的GI日记，遵循FDA和COSMIN指南。目的：在ETI开始前14天和后14-28天，使用CFAbd-day2day前瞻性地捕获AS的即时动态。此外,我们的目标是提供有关变化敏感性的新型PROM的验证步骤.方法：开发CFAbd-day2day，反复咨询焦点小组（社区语音=pwCF及其代理人和来自不同领域的CF专家）。在新的ETI治疗之前和期间，pwCF用CFAbd-day2day每天对AS进行前瞻性评分。结果：总之，在五个CF中心参加的45个pwCF在ETI开始之前（平均±sd：14±7天）和之后（平均±sd：28±23天）前瞻性地完成了CFAbd-day2天。一方面,在ETI启动后的3-4周时间范围内，累积分数显着下降，与治疗前2周相比。另一方面,许多在ETI之前表现出相对稳定的AS水平的患者报告说,在使用高效CFTR调节剂治疗的头几天发生了变化.在治疗的前14天，疼痛和肠胃气胀等因素在高达21%的患者中增加，但在15-27天改善了.结论：CFAbd-day2day，专门开发并在验证过程中前瞻性捕获pwCF中的胃肠道症状，为接受ETI新疗法的pwCF中AS的动力学提供了新的实质性见解。这种新颖的工具也有助于前瞻性地监测患有特定胃肠道问题的患者。日记的国际实施和进一步的验证步骤正在进行中。
