Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

Burgel, Pierre‐Régis; Durieu, I.; Chiron, R.; Danner-Boucher, Isabelle; Prévotat, A.; Grenet, Dominique; Marguet, Christophe; Reynaud‐Gaubert, Martine; Mély, Laurent; Fanton, Annlyse; Quétant, S.; Lemonnier, Lydie; Paillasseur, Jean-Louis; Silva, Jennifer Da; Martin, Clémence; Andréjak, Claire; Bécourt, Arnaud; Mounard, Julie; Poulet, Claire; Rames, Cinthia; Talleux, Marie; Chevalier, Marie-Chantal; Darviot, E.; Jouvenot, Marie; Marien, Caroline; Paris, Audrey; Pélatan, C.; Person, Christine; Priou, Pascaline; Troussier, Françoise; Urban, T.; Dalphin, Marie‐Laure; Dalphin, Jean‐Charles; Ladaurade, Alice; Pernet, D.; Richaud-Thiriez, Bénédicte; Roux-Claude, Pauline; Blanc, Nathalia; Boisserie-Lacroix, V.; Bui, Stéphanie; Collet, Cyrielle; Debelleix, Stéphane; Macey, Julie; Bergot, Emmanuel; Brouard, J.; Campbell, Karine; Laurans, M.; Ribault, Virginie; Borderon, Corinne; Héraud, M; Labbé, G.; Montcouquiol, Sylvie; Petit, Isabelle; Ruivard, M.; Delestrain, Céline; Douvry, B.; Epaud, Ralph; Maître, Bernard; Remus, Natascha; Beltramo, Guillaume; Houzel, Anne; Huet, Frédéric; Perez, Stéphanie; Boldron-Ghaddar, Amale; Scalbert, Manuëla; Bouzioukh, Rabah; Simon, Charles E.; Camara, B.; Hamidfar, Rébecca; Llerena, C.; Pin, Isabelle; Deschildre, A.; Gicquello, Alice; Rouzic, Olivier Le; Leroy, Clara; Paris, Nicolas; Pérez, Thierry; Thumerelle, C.; Turck, Dominique; Wizla, N.; Dupuy-Grasset, Magali; Languepin, J.; Masson-Rouchaud, Alexandra; Menetrey, Céline; Durupt, S.; L’Excellent, S.; Nové-Josserand, Raphaële; Ohlmann, Camille; Reix, P.; Reynaud, Quitterie; Werck‐Gallois, Marie‐Christine; Baravalle, Mélissandre; Coltey, Bérangère; Desmazes-Dufeu, N.; Dubus, Jean‐Christophe; Gautier, C.; Rey, Jean-Baptiste; Stremler, Nathalie; Caimmi, Davide; Devrait, Margot; Moreau, Johan; Billon, Y.; Blondé, Aurore; Guillaumot, Anne; Kiefer, Sébastien; Peretti, L; Tatopoulos, Aurélie; Tiotiu, Angélica; Benhamida, Myriam; Bihouée, Tiphaine; Eschapasse, E.; Tissot, A. N.; Giannantonio, Marie; Leroy, Sylvie; Piccini-Bailly, C.; Pradelli, J.; Messika, Jonathan; Boussaud, V.; Carlier, Nicolas; Honoré, Isabelle; Hubert, D.; Kanaan, R.; Bailly-Botuha, Céline; Chedevergne, F.; Blic, J. de; Delacourt, Christophe; Drummond, David; Fauroux, Brigitte; Karila, C.; Bourgeois, M. Le; Sermet, Isabelle; Delaisi, Bertrand; Gérardin, M.; Houdouin, Véronique; Leclainche, Laurence; Aubertin, Guillaume; Berdah, Laura; Clément, Annick; Corvol, Harriet; Nathan, Nadia; Prévost, Bertrand; Richard, Nicolas; Tamalet, Aline; Taytard, Jessica; Thouvenin, Guillaume; Tourniaire, B.; Abély, M.; Bessaci-Kabouya, K.; Dury, Sandra; Ravoninjatovo, Bruno; Dabadie, A.; Dagorne, M.; Deneuville, E.; Jamin, Marie; Ribault, Mélanie; Vigier, C.; Belleguic, Chantal; Brinchault, Graziella; Desrues, B.; Barzic, Audrey; Dirou-Prigent, Anne; Bihan, Jean Le; Ramel, Sophie; Revert, K.; Ropars, Thomas; Couderc, L.; Dominique, S.; Morisse-Pradier, H.; Pramil, S.; Thiberville, Luc; Allou, Nathalie; Enaud, Laurent; Gachelin, Elsa; Huchot, É.; Payet, A.; Périsson, Caroline; Piyaraly, S.; Valois, Sophie; Herzog, Audrey; Kessler, Romain; Porzio, Michele; Weiss, Laurence; Beaumont, L.; Brugière, Olivier; Colin, Sylvie; Verdiere, de; Cuquemelle, E.; Miranda, S. De; Hamid, Adbdul Monem; Parquin, François; Picard, C.; Roux, Antoine; Roy, Charlotte; Brémont, F.; Didier, A.; Dupuis, Marion; Faviez, G.; Labouret, Géraldine; Mittaine, M.; Murris-Espin, M.; Roditis, Léa; Cosson, Laure; Diot, Patrice; Flament, Thomas; Giraut, C.; Mankikian, Julie; Arnouat, Baptiste; Mousset, Gaétane; Storni, V.; Vigneron, Philippe; Coirier-Duet, Emmanuelle; Gabsi, Asma

doi:10.1164/rccm.202011-4153oc

Cited by 177 publications

(118 citation statements)

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“…Recently, the efficacy and safety of lumacaftor and ivacaftor have been demonstrated in the 2–5 and 6–11 years populations, allowing the indications to be extended to a broader pediatric population [ 13 , 14 ]. Otherwise recent data on the double tezacaftor– ivacaftor combination [ 15 , 16 ], and more recently, triple therapy, combining three CFTR modulators, elexacaftor–tezacaftor–ivacaftor, demonstrated extremely promising safety and clinical efficacy profiles [ 17 , 18 , 19 , 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor

Arnaud

Bel

Reynaud‐Gaubert

et al. 2021

JCM

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Background: As Cystic Fibrosis (CF) treatments drastically improved in recent years, tools to assess their efficiency need to be properly evaluated, especially cross-sectional imaging techniques. High-resolution computed tomography (HRCT) scan response to combined lumacaftor- ivacaftor therapy (Orkambi®) in patients with homozygous for F508del CFTR has not yet been assessed. Methods: We conducted a retrospective observational study in two French reference centers in CF in Marseille hospitals, including teenagers (>12 years old) and adults (>18 years) who had received lumacaftor–ivacaftor and for whom we had at disposal at least two CT scans, one at before therapy and one at least six months after therapy start. CT scoring was performed by using the modified version of the Brody score. Results: 34 patients have been included. The mean age was 26 years (12–56 years). There was a significant decrease in the total CT score (65.5 to 60.3, p = 0.049) and mucous plugging subscore (12.3 to 8.7, p = 0.009). Peribronchial wall thickening (PWT) was significantly improved only in the adult group (29.1 to 27.0, p = 0.04). Improvements in total score, peribronchial thickening, and mucous pluggings were significantly correlated with improvement in FEV1 (forced expiratory volume in 1 s). Conclusions: Treatment with lumacaftor–ivacaftor was associated with a significant improvement in the total CT score, which was mainly related to an improvement in mucous pluggings.

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Section: Discussionmentioning

confidence: 99%

Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor

Arnaud

Bel

Reynaud‐Gaubert

et al. 2021

JCM

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“…The clinical trials of ETI in pwCF who were F / F or heterozygous for F and MF , RF , or G involved patients with mild‐moderate lung disease, 1 , 2 , 3 but improvements have also been obtained in pwCF with advanced lung disease, and these have often obviated the need for lung transplantation. 4 , 5 , 6 , 7 , 8…”

Section: Discussionmentioning

confidence: 99%

Elexacaftor/tezacaftor/ivacaftor as rescue therapy in a patient with the cystic fibrosis genotype F508DEL/G1244E

Salvatore

Colangelo

D’Andria

et al. 2021

Clinical Case Reports

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“…The phase 2/3 clinical trials with CFTR modulators use inclusion criteria that exclude subjects with either or high pulmonary function, ppFEV 1 < 40% or higher than 90%, respectively. A large prospective observational study showed that pwCF with a ppFEV 1 below 40% that use the triple therapy as part of a "temporary use program" also show great response with a mean increase of ppFEV 1 of 15.1% [50]. Although responses on group level are impressive, there is still a wide range in response with ppFEV 1 change ranging from −2.5 to > 20% [48].…”

Section: Symptomatic Treatmentmentioning

confidence: 99%

A new era for people with cystic fibrosis

et al. 2021

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Cystic fibrosis is the most prevalent inherited disease caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The impaired electrolyte homeostasis caused by the mutated or absent protein leads to symptoms in multiple organ systems. However, the pulmonary manifestation with chronic infections and eventually respiratory failure remains the most important threat. Until one decade ago, only symptomatic treatment was available. However, since 2012, different combinations of CFTR modulators are available for people with cystic fibrosis (pwCF) that carry different mutations. The advent of these drugs has impressively changed life expectancy and quality of life in people with cystic fibrosis and raised new challenges regarding long-term complications and tapering of conventional therapies.Conclusion: In this review, we provide an update on the latest developments around diagnostics, treatment, and prognosis of pwCF. What is Known:• Cystic fibrosis is an incurable and life-shortening disease asking for life-long symptomatic treatment.• Three combination CFTR modulating drugs has gained marked approval over the last 10 years. What is New:• The emerge of new (modulating) therapies contribute to the increasing life expectancy.• A high unmet need to develop new therapies for people with CF who cannot access or benefit from these drugs remains. This review gives an update on the current status.

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Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

Cited by 177 publications

References 19 publications

Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor

Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor

Elexacaftor/tezacaftor/ivacaftor as rescue therapy in a patient with the cystic fibrosis genotype F508DEL/G1244E

A new era for people with cystic fibrosis

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