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法国的 elexacaftor/tezacaftor/ivacaftor 同情计划针对患有晚期肺病且无 F508del CFTR 变异的囊性纤维化患者
European Respiratory Journal
(
IF
16.6
)
Pub Date : 2023-05-05
, DOI:
10.1183/13993003.02437-2022
Pierre-Régis Burgel
1,
2,
3
,
Isabelle Sermet-Gaudelus
3,
4,
5
,
Isabelle Durieu
3,
6,
7
,
Reem Kanaan
2,
3
,
Julie Macey
8
,
Dominique Grenet
9
,
Michele Porzio
10
,
Nathalie Coolen-Allou
11
,
Raphael Chiron
12
,
Christophe Marguet
13
,
Benoit Douvry
14
,
Nadine Dufeu
15
,
Isabelle Danner-Boucher
16
,
Pierre Foucaud
17
,
Lydie Lemonnier
17
,
Emmanuelle Girodon
18
,
Jennifer Da Silva
2,
3
,
Clémence Martin
2,
3,
19
,
Affiliation
- Université Paris-Cité, Institut Cochin, Inserm U1016, Paris, France
- Respiratory Medicine and Cystic Fibrosis National Reference Center; Cochin Hospital; Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
- ERN-Lung CF network, Frankfurt, Germany.
- Centre de de Référence Maladies Rares, Mucoviscidose et affections liées à CFTR, Pneumologie Pédiatrique et Allergologie, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Université Paris-Cité, Institut Necker Enfants Malades, INSERM U1151, Paris, France.
- Centre de référence Adulte de la Mucoviscidose, Service de médecine interne, Hospices civils de Lyon, Pierre Bénite, France.
- Université de Lyon, Équipe d'Accueil Health Services and Performance Research (HESPER) 7425, Lyon, France.
- Respiratory Medicine and Cystic Fibrosis Center, CHU de Bordeaux, Bordeaux, France.
- CRCM - Centre de Transplantation Pulmonaire. Service de pneumologie, hôpital Foch, Suresnes, France.
- Department of Respiratory Medicine and Cystic Fibrosis Center, Federation of Translational Medicine of Strasbourg (FMTS), University Hospitals, Strasbourg, France.
- Centre Hospitalier Universitaire Félix Guyon, Saint Denis, La Réunion, France.
- Cystic Fibrosis Center, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
- Pediatric Respiratory Disease and Cystic Fibrosis Center, Hospital, UNIROUEN, Inserm EA 2656, Rouen University Hospital, Normandie Univ, Rouen, France.
- Service de Pneumologie, Centre Hospitalier Intercommunal, FHU SENEC, Créteil, France.
- Department of Respiratory Medicine and Lung Transplantation, Aix Marseille Univ, APHM, Hôpital Nord, Marseille, France.
- Service de Pneumologie, L'Institut Du Thorax, CHU Nantes, Nantes, France.
- Association Vaincre la Mucoviscidose, Paris, France.
- APHP.Centre-Université de Paris Cité, Service de Médecine Génomique des Maladies de Système et d'Organe, Hôpital Cochin, Paris, France.
- Université Paris-Cité, Institut Cochin, Inserm U1016, Paris, France.
背景
欧洲药品管理局已批准囊性纤维化跨膜电导调节剂 (CFTR) 调节剂组合 elexacaftor/tezacaftor/ivacaftor (ETI) 用于携带至少一种 F508del 变异的囊性纤维化 (CF) 患者。美国食品和药物管理局 (FDA) 还批准 ETI 用于治疗携带 177 种罕见变异之一的 CF 患者。
方法
一项观察性研究旨在评估 ETI 对欧洲不符合 ETI 资格的患有晚期肺病的 CF 患者的有效性。所有没有 F508del 变异和晚期肺部疾病的患者（定义为预测用力呼气量百分比 (ppFEV 1 ) <40 id=29>1 。
结果
在该计划纳入的首批 84 名 CF 患者中，ETI 对 45 名 (54%) 名患者有效，39 名 (46%) 名患者被认为是无反应者。在应答者中，45 人中有 22 人 (49%) 携带CFTR变体，该变体目前尚未获得 FDA 批准的 ETI 资格。重要的临床益处，包括暂停肺移植指征、汗液氯化物浓度中位数（四分位距 (IQR)）显着降低 –30 (–14––43) mmol·L –1 (n=42；p<在治疗有效的患者中观察到 0 id=32>1 +10.0 (6.0–20.5) 个百分点 (n=44；p<0.0001)。
结论
在患有晚期肺病和目前尚未批准用于 ETI 的CFTR变异的一大部分 CF 患者中观察到临床获益。
"点击查看英文标题和摘要"
The French compassionate programme of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant
Background
The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (CF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for people with CF carrying one of 177 rare variants.
Methods
An observational study was conducted to evaluate the effectiveness of ETI in people with CF with advanced lung disease who were not eligible for ETI in Europe. All patients with no F508del variant and advanced lung disease (defined as having a percent predicted forced expiratory volume (ppFEV1) <40% and/or being under evaluation for lung transplantation) and enrolled in the French compassionate programme initiated ETI at recommended doses. Effectiveness was evaluated by a centralised adjudication committee at 4–6 weeks in terms of clinical manifestations, sweat chloride concentration and ppFEV1.
Results
Among the first 84 people with CF included in the programme, ETI was effective in 45 (54%), and 39 (46%) were considered to be nonresponders. Among the responders, 22 (49%) out of 45 carried a CFTR variant that is not currently approved by the FDA for ETI eligibility. Important clinical benefits, including suspending the indication for lung transplantation, a significant decrease in sweat chloride concentration by a median (interquartile range (IQR)) –30 (–14––43) mmol·L–1 (n=42; p<0.0001) and an improvement in ppFEV1 by +10.0 (6.0–20.5) percentage points (n=44; p<0.0001), were observed in those for whom treatment was effective.
Conclusion
Clinical benefits were observed in a large subset of people with CF with advanced lung disease and CFTR variants not currently approved for ETI.
更新日期：2023-05-05
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