Identification of early changes in multiple biomarkers following CFTR modulator initiation in patients with cystic fibrosis.

IF 3 3区医学 Q2 RESPIRATORY SYSTEM

Therapeutic Advances in Respiratory Disease Pub Date : 2025-01-01 Epub Date: 2025-10-09 DOI:10.1177/17534666251376211

Pascal Heer, Clara Fernandez Elviro, Angela Koutsokera, Anne Mornand, Isabelle Rochat, Nicolas Regamey, Sylvain Blanchon

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引用次数: 0

Abstract

Background: There are currently no early parameters that allow prediction of long-term responses to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator treatment on an individual level.

Objectives: To identify early parameters measured within 7 to 14 days after initiation of treatment with a CFTR modulator to assess CFTR modulator efficacy.

Study design: Prospective observational study of patients diagnosed with CF who begin elexacaftor/tezacaftor/ivacaftor (ETI) therapy at 3 CF clinics in Switzerland (Geneva, Lausanne, Lucerne).

Methods: Standardized measurements were taken within 2 months prior to and 7 to 14 days after starting CFTR modulator treatment.

Results: ETI treatment was started on 47 patients [median age: 12 years] of whom 12 (26%) were switching from lumacaftor/ivacaftor (n = 8) or tezacaftor/ivacaftor (n = 4) to ETI. A significant early treatment effect was observed for BMI z-score (p < 0.001) and inflammatory parameters (white blood cells (p = 0.006), neutrophils (p = 0.006), immunoglobulin G (p = 0.012), and fecal calprotectin (p = 0.002)). In CFTR functional assays, sweat chloride concentration and nasal potential difference testing [Δlow-chloride+isoproterenol, Sermet score, and Wilschanski index] improved significantly (all p < 0.001). Improvement was also observed in lung function (FVC, FEV₁, MMEF_25-75, LCI_2.5%) (all p < 0.001). No changes were found for blood pressure, SpO₂, respiratory rate, erythrocyte sedimentation rate, C-reactive protein, and fecal elastase.

Conclusion: This study identified clinical, biologic, and functional parameters showing treatment effect early after initiation of CFTR modulator therapy. These parameters may serve as potential predictors of long-term responses to CFTR modulator treatment.

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囊性纤维化患者CFTR调节剂启动后多种生物标志物早期变化的鉴定

背景：目前还没有早期参数可以预测个体水平上囊性纤维化跨膜传导调节剂（CFTR）治疗的长期反应。目的：确定CFTR调节剂治疗开始后7至14天内测量的早期参数，以评估CFTR调节剂的疗效。研究设计：对在瑞士（日内瓦、洛桑、卢塞恩）3家CF诊所接受elexaftor /tezacaftor/ivacaftor （ETI）治疗的CF患者进行前瞻性观察研究。方法：在CFTR调制器治疗前2个月和开始治疗后7 ~ 14天进行标准化测量。结果：47例患者（中位年龄：12岁）开始接受ETI治疗，其中12例（26%）从lumacaftor/ivacaftor （n = 8）或tezacaftor/ivacaftor （n = 4）转为ETI治疗。BMI z-score （p = 0.006）、中性粒细胞（p = 0.006）、免疫球蛋白G （p = 0.012）和粪钙保护蛋白（p = 0.002）的早期治疗效果显著。在CFTR功能测试中，汗液氯浓度和鼻电位差测试[Δlow-chloride+异丙肾上腺素，Sermet评分和Wilschanski指数]显著改善（所有p 1， MMEF25-75, LCI2.5%）（所有p 2，呼吸率，红细胞沉降率，c反应蛋白和粪便弹性酶）。结论：本研究确定了CFTR调节剂治疗开始后早期显示治疗效果的临床、生物学和功能参数。这些参数可能作为对CFTR调节剂治疗的长期反应的潜在预测因子。

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

Therapeutic Advances in Respiratory Disease RESPIRATORY SYSTEM-

CiteScore

6.90

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Respiratory Disease delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of respiratory disease.