Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis.

Lumacaftor-Ivacaftor 在囊性纤维化患者中的真实安全性和有效性。

  • 影响因子:5.24
  • DOI:10.1164/rccm.201906-1227OC
  • 作者列表:"Burgel PR","Munck A","Durieu I","Chiron R","Mely L","Prevotat A","Murris-Espin M","Porzio M","Abely M","Reix P","Marguet C","Macey J","Sermet-Gaudelus I","Corvol H","Bui S","Lemonnier L","Dehillotte C","Da Silva J","Paillasseur JL","Hubert D","French Cystic Fibrosis Reference Network Study Group.
  • 发表时间:2020-01-15

:Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.


: 原理: Lumacaftor-ivacaftor 是一种 CFTR (囊性纤维化跨膜传导调节因子) 调节剂组合,最近被批准用于囊性纤维化 (CF) 纯合子 Phe508del 突变患者。目的: 在真实的批准后环境中,评价 lumacaftor-ivacaftor 在青少年 (≥ 12 岁) 和成人 (≥ 18 岁) 中的安全性和有效性。方法:该研究在法国的 47 个 CF 参考中心进行。从 1月1日至 2016年12月31日启动 lumacaftor-ivacaftor 的所有患者均符合条件。按照法国 CF 学习协会的建议,对患者进行 lumacaftor-ivacaftor 治疗第一年的安全性和有效性评价。测量和主要结果: 在启动 lumacaftor-ivacaftor 的 845 例患者 (292 例青少年和 553 例成人) 中,18.2% 例 (154 例患者) 因呼吸系统中断治疗 (48.1% 例,74 例患者)或非呼吸 (27.9%,43 例患者) 不良事件。在多变量 logistic 回归中,与停药率增加相关的因素包括成人年龄组,预计 FEV1 (ppFEV1) 百分比小于 40%, 和 lumacaftor-ivacaftor 开始前一年静脉注射抗生素疗程的次数。持续暴露于 lumacaftor-ivacaftor 的患者显示 ppFEV1 绝对增加 (+ 3.67%),体重指数增加 (+ 0.73千克/m2), 静脉注射抗生素疗程减少 35%。停止治疗的患者 ppFEV1 显著降低,体重指数无改善或静脉注射抗生素疗程减少。结论: Lumacaftor-ivacaftor 与耐受治疗的患者肺部疾病和营养状况的改善相关。停用 lumacaftor-ivacaftor 的成人,通常由于不良事件,被发现具有临床恶化的高风险。



作者列表:["Vadillo C","Nieto MA","Romero-Bueno F","Leon L","Sanchez-Pernaute O","Rodriguez-Nieto MJ","Freites D","Jover JA","Álvarez-Sala JL","Abasolo L"]

METHODS:OBJECTIVES:To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS:A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS:A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION:RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified. Key words: rheumatoid arthritis, interstitial lung disease, observational study, rituximab and prognosis

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作者列表:["Shibaki, Ryota","Murakami, Shuji","Matsumoto, Yuji","Yoshida, Tatsuya","Goto, Yasushi","Kanda, Shintaro","Horinouchi, Hidehito","Fujiwara, Yutaka","Yamamoto, Nobuyuki","Kusumoto, Masahiko","Yamamoto, Noboru","Ohe, Yuichiro"]

METHODS:The safety of anti-programmed cell death 1 (PD-1) antibody for patients with preexisting interstitial lung disease (ILD) remains unknown. The aim of this study was to evaluate the dependence of preexisting ILD on anti-PD-1 antibody-induced pneumonitis in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the association of preexisting ILD with the incidence, radiographic pattern, and outcome of pneumonitis in NSCLC patients receiving anti-PD-1 antibody. A total of 331 patients were included in this study. Of these patients, 17 had preexisting ILD. The incidence of pneumonitis was higher among the patients with preexisting ILD than among those without preexisting ILD (29% vs. 10%, P  = 0.027). The distributions of the CT appearances at the onset of anti-PD-1 antibody-induced pneumonitis were as follows: for the patients with preexisting ILD, two patients (40%) had diffuse alveolar damage (DAD), one patient each with organizing pneumonia-like (OP), hypersensitivity pneumonitis (HP), and other patterns (20% each); for the patients without preexisting ILD, 19 patients (61%) had OP, 8 (26%) had HP, 3 (10%) had DAD, and 1 (3.2%) had other patterns. The median onset time from the initiation of anti-PD-1 antibody treatment until the development of pneumonitis was 1.3 months (range 0.3–2.1 months) for the patients with preexisting ILD and 2.3 months (range 0.2–14.6 months) for the patients without preexisting ILD. Careful attention to the development of pneumonitis is needed, especially within the first 3 months after the start of anti-PD-1 antibody treatment, when using anti-PD-1 antibody to treat patients with preexisting ILD.

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来源期刊:New biotechnology
作者列表:["Sousa SA","Soares-Castro P","Seixas AMM","Feliciano JR","Balugas B","Barreto C","Pereira L","Santos PM","Leitão JH"]

METHODS::Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous multidrug resistant organisms and opportunistic pathogens capable of causing life threatening lung infections among cystic fibrosis (CF) patients. No effective therapies are currently available to eradicate Bcc bacteria from CF patients, as these organisms are inherently resistant to the majority of clinically available antimicrobials. An immunoproteomics approach was used to identify Bcc proteins that stimulate the humoral immune response of the CF host, using bacterial cells grown under conditions mimicking the CF lung environment and serum samples from CF patients with a clinical record of Bcc infection. 24 proteins of the Bcc strain B. cenocepacia J2315 were identified as immunoreactive, 19 here reported as immunogenic for the first time. Ten proteins were predicted as extracytoplasmic, 9 of them being conserved in Bcc genomes. The immunogenic Bcc extracytoplasmic proteins are potential targets for development of novel therapeutic strategies and diagnostic tools to protect patients against the onset of chronic Bcc lung infections.