BACKGROUND: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF. METHODS: This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months. FINDINGS: The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV(1)) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p < 0.0001), body mass index (BMI) z-score increased by 0.3 (95% CI 0.3-0.4, p < 0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4 kg/m(2) (95% CI 1.3-1.4, p < 0.0001), pulmonary exacerbations decreased by 75.9% (p < 0.0001) and mean sweat chloride concentration decreased by 50.9 mmol/L (95% CI -52.6, -49.3, p < 0.0001). Improvements in ppFEV(1) over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment. INTERPRETATION: These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele. FUNDING: None.
- Sutharsan, Sivagurunathan
- Dillenhoefer, Stefanie
- Welsner, Matthias
- Stehling, Florian
- Brinkmann, Folke
- Burkhart, Manuel
- Ellemunter, Helmut
- Dittrich, Anna-Maria
- Smaczny, Christina
- Eickmeier, Olaf
- Kappler, Matthias
- Schwarz, Carsten
- Sieber, Sarah
- Naehrig, Susanne
- Naehrlich, Lutz
- Tenbrock, Klaus
- Pfannenstiel, Claus
- Steffen, Dirk
- Meister, Jochen
- Welzenbach, Britta
- Scharschinger, Anette
- Kratz, Markus
- Pincus, Maike
- Tenenbaum, Tobias
- Stahl, Mirjam
- Landwehr, Kerstin
- Dillenhöfer, Stefanie
- Kössel, Hans
- Kaiser, Petra
- Käding, Manfred
- Stolz, Simone
- Blaas, Stefan
- Hammermann, Jutta
- Gappa, Monika
- Schuster, Antje
- Spittel, Dana
- Zirlik, Sabine
- Schmitt, Sabina
- Stehling, Florian
- Sutharsan, Sivagurunathan
- Bargon, Joachim
- Cremer, Malte
- Smaczny, Christina
- Fähndrich, Sebastian
- Heinzmann, Andrea
- Nährlich, Lutz
- Kuhnert, Stefan
- Schmidt, Sebastian
- Wollschläger, Bettina
- Nolde, Anna
- Held, Inka
- Kamin, Wolfgang
- Ringshausen, Felix C.
- Dittrich, Anna-Maria
- Wege, Sabine
- Sommerburg, Olaf
- Geier, Norbert
- Fleser, Sara Lisa
- Wilkens, Heinrike
- Ellemunter, Helmut
- Lorenz, Michael
- Vöhringer, Paul
- Schebek, Martin
- Timke, Christian
- Bobis, Ingrid
- Nüßlein, Thomas
- Dieninghoff, Doris
- Rietschel, Ernst
- Klinkhammer, Bastian
- Prenzel, Freerk
- Wald, Alexandra
- Kempa, Axel
- Brinkmann, Folke
- Lücke, Eva
- Adams, Ines
- Poplawska, Krystyna
- Lehmkühler, Simone
- Bauck, Monika
- Pfülb, Anne
- Fischer, Rainald
- Schopper, Gudrun
- Nährig, Susanne
- Griese, Matthias
- Grosse, Jörg
- Küster, Peter
- KinderHolger Köster, Birte
- Büsing, Susanne
- Pohl, Margarethe
- Schwarz, Carsten
- Artlich, Andreas
- Kiefer, Alexander
- Ballmann, Manfred
- Gjorgjevski, Nikola
- Rose, Markus A.
- Ruf, Friederike
- Mahlberg, Rolf
- Thomas, Wolfgang
- Graepler, Ute
- Bode, Sebastian
- hilipp, Meyn
- Rosenecker, Josef
- Koerner, Cordula
- Keller, Klaus-Michael
- Teßmer, Tina
- Hebestreit, Helge
- Lohse, Gerhild
Keywords
- Body mass index
- Cystic fibrosis
- Elexacaftor/tezacaftor/ivacaftor
- Lung function
- Pulmonary exacerbation
- Real-world evidence
- Sweat chloride
- Celtaxsys, Vertex Pharmaceuticals, Boehringer Ingelheim, Corbus Pharmaceuticals,
- Insmed Germany GmbH and Ionis Pharmaceuticals outside the submitted work. SD
- participated in the Advance program, financially supported by Vertex
- Pharmaceuticals. MW received personal fees from Vertex Pharmaceuticals, Chiesi,
- CSL Behring, and Grifols outside of the submitted work. CSm received personal
- fees from Vertex Pharmaceuticals outside the submitted work. FS has no conflict
- of interest. FB has no conflict of interest. MB receives payments from
- Mukoviszidose Institut gGmbH. AMD received personal fees from Vertex outside of
- the submitted work and institutional payments from Vertex for the conduct of
- clinical studies. HE received personal fees Vertex Pharmaceuticals and Insmed
- Germany GmbH outside the submitted work. CS received personal fees or grants from
- Chiesi, GlaxoSmithKline, Boehringer Ingelheim, Vertex Pharmaceuticals and GILEAD
- outside the submitted work. OE received personal fees or grants from Boerhringer
- Ingelheim, Chiesi, Corbus Pharmaceuticals, GILEAD, Novartis, Vertex
- Pharmaceuticals outside the submitted work. MK has no conflict of interest. SaS
- receives payments for statistical analysis of data that were made to STAT-UP
- Statistical Consulting & Data Science GmbH. SN received institutional payments
- from Vertex for the conduct of clinical studies. LN received institutional
- payments from The German Center of Lung research and Vertex Pharmaceuticals for
- the conduct of clinical studies, was the medical lead of the German CF Registry
- and the Pharmacovigilance Study manager of the European Cystic Fibrosis Society
- Patient Registry and received Medial Writing support from Articulate Science.
