WS01.01Predicting future pulmonary exacerbation (PEx) rates for cystic fibrosis (CF) clinical trials

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.492

D. VanDevanter , C. O'Rourke , K. Odem-Davis , J. Clancy , M. Konstan , N. Mayer Hamblett

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引用次数: 0

Abstract

Objectives

Due to the clinical importance of CF pulmonary exacerbations (PEx), regulators accept PEx rate difference as clinical trial efficacy endpoint. Although CFTR modulators have reduced overall PEx rates, this endpoint remains relevant to future CF drug development, provided study populations can be enriched for individuals with elevated PEx risk. Although the number of prior-year PEx treated with intravenous antimicrobials (IV-PEx) strongly predicts future IV-PEx risk [JCF. 2016;15(3):372-9], IV-PEx incidence has fallen to a point where it has little if any utility as a clinical trial endpoint: today PEx treated with antibiotics by any route (anyPEx) are studied despite little knowledge of associations between prior year anyPEx number and future PEx rates. We tested whether prior year anyPEX number predicted future anyPEx rates in CF adults receiving and not receiving the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI).

Methods

CF adults with data present in the CF Foundation Patient Registry (CFFPR) in 2022 & 2023 were studied, provided they had received either

a) ETI or

b) no modulators in both years.

AnyPEx were counted; treatments starting <28 days of a previous treatment start were considered part of the previous PEx. 2023 PEx rates were compared among subgroups having 0, 1-2, or 3+ PEx in 2022.

Results

PEx counted in 2022 strongly correlated with mean 2023 PEx rates within both the ETI and No Modulator groups (P<.001, table), with the mean rate for the entire ETI group lower than that of the No Modulator group, as well as within subgroups with 0 and 1-2 PEx in 2022 (table).

Empty Cell	No 2022 PEx	One or Two 2022 PEx	Three plus 2022 PEx	Overall
2023 ETI group PEx rate (N)	0.23/yr (9452)	0.78/yr (3267)	2.19/yr (469)	0.43/yr (13,188)
2023 No Modulator group PEx rate (N)	0.32/yr (1356)	1.08/yr (633)	2.37/yr (159)	0.70/yr (2148)
Relative rate (ETI/No Modulator), [95% CI]	0.71 [0.63, 0.79]	0.72 [0.65, 0.80]	0.92 [0.78, 1.10]	0.62 [0.57, 0.68]

Conclusions

An unmet need for therapeutic interventions to reduce CF PEx risk remains, even in populations receiving CFTR modulators. The number of anyPEx counted in a prior year strongly predict future anyPEx rates in adults, suggesting an enrichment approach for CF trials using difference in PEx rates as an efficacy endpoint.

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预测囊性纤维化（CF）临床试验中未来肺恶化（PEx）率

由于CF肺恶化（PEx）的临床重要性，监管机构接受PEx率差异作为临床试验疗效终点。尽管CFTR调节剂降低了总体PEx率，但如果研究人群中PEx风险升高的个体能够得到丰富，这一终点仍然与未来CF药物开发相关。尽管静脉注射抗菌剂（IV-PEx）治疗的前一年PEx的数量强烈预测未来IV-PEx的风险[JCF]。[2016;15(3):372-9]， IV-PEx的发病率已经下降到几乎没有任何效用作为临床试验终点的地步：尽管对上一年的anyPEx数量与未来的PEx发病率之间的关系知之甚少，但今天用任何途径的抗生素治疗的PEx （anyPEx）仍在研究中。我们测试了前一年的anyPEX数字是否预测了接受和未接受CFTR调制器萃取剂/ tezacftor /ivacaftor （ETI）的CF成人未来的anyPEX率。方法：2022年CF基金会患者登记（CFFPR）中存在数据的成人CF；研究了2023个，前提是它们在两年内都接受了ETI或没有调制器。任何pex都被计数；先前治疗开始28天的治疗被认为是先前PEx的一部分。2023年PEx率在2022年的0、1-2或3+ PEx亚组之间进行比较。结果在ETI和No Modulator组中，2022年的spex计数与2023年的平均PEx率密切相关(P<；001，表)，整个ETI组的平均发生率低于No Modulator组，以及2022年PEx为0和1-2的子组（表）。空细胞No 2022 PExOne or Two 2022 PExThree + 2022 PExOverall2023 ETI组PEx率(N)0.23/年（9452）0.78/年（3267）2.19/年（469）0.43/年（13,188）2023无调节剂组PEx率(N)0.32/年（1356）1.08/年（633）2.37/年（159）0.70/年（2148）相对率（ETI/No Modulator）， [95% CI]0.71[0.63, 0.79]0.72[0.65, 0.80]0.92[0.78, 1.10]0.62[0.57, 0.68]结论即使在接受CFTR调节剂的人群中，仍然存在降低CF PEx风险的治疗干预需求。前一年统计的anyPEx数量强有力地预测了成人未来的anyPEx率，建议CF试验采用PEx率差异作为疗效终点的富集方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.