The Lancet Regional Health. Europe (Sep 2023)

Impact of elexacaftor/tezacaftor/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: real-world evidence from the German CF RegistryResearch in context

  • Sivagurunathan Sutharsan,
  • Stefanie Dillenhoefer,
  • Matthias Welsner,
  • Florian Stehling,
  • Folke Brinkmann,
  • Manuel Burkhart,
  • Helmut Ellemunter,
  • Anna-Maria Dittrich,
  • Christina Smaczny,
  • Olaf Eickmeier,
  • Matthias Kappler,
  • Carsten Schwarz,
  • Sarah Sieber,
  • Susanne Naehrig,
  • Lutz Naehrlich,
  • Klaus Tenbrock,
  • Claus Pfannenstiel,
  • Dirk Steffen,
  • Jochen Meister,
  • Britta Welzenbach,
  • Anette Scharschinger,
  • Markus Kratz,
  • Maike Pincus,
  • Tobias Tenenbaum,
  • Mirjam Stahl,
  • Kerstin Landwehr,
  • Stefanie Dillenhöfer,
  • Hans Kössel,
  • Petra Kaiser,
  • Manfred Käding,
  • Simone Stolz,
  • Stefan Blaas,
  • Jutta Hammermann,
  • Monika Gappa,
  • Antje Schuster,
  • Dana Spittel,
  • Sabine Zirlik,
  • Sabina Schmitt,
  • Florian Stehling,
  • Sivagurunathan Sutharsan,
  • Joachim Bargon,
  • Malte Cremer,
  • Christina Smaczny,
  • Sebastian Fähndrich,
  • Andrea Heinzmann,
  • Lutz Nährlich,
  • Stefan Kuhnert,
  • Sebastian Schmidt,
  • Bettina Wollschläger,
  • Anna Nolde,
  • Inka Held,
  • Wolfgang Kamin,
  • Felix C. Ringshausen,
  • Anna-Maria Dittrich,
  • Sabine Wege,
  • Olaf Sommerburg,
  • Norbert Geier,
  • Sara Lisa Fleser,
  • Heinrike Wilkens,
  • Helmut Ellemunter,
  • Michael Lorenz,
  • Paul Vöhringer,
  • Martin Schebek,
  • Christian Timke,
  • Ingrid Bobis,
  • Thomas Nüßlein,
  • Doris Dieninghoff,
  • Ernst Rietschel,
  • Bastian Klinkhammer,
  • Freerk Prenzel,
  • Alexandra Wald,
  • Axel Kempa,
  • Folke Brinkmann,
  • Eva Lücke,
  • Ines Adams,
  • Krystyna Poplawska,
  • Simone Lehmkühler,
  • Monika Bauck,
  • Anne Pfülb,
  • Rainald Fischer,
  • Gudrun Schopper,
  • Susanne Nährig,
  • Matthias Griese,
  • Jörg Grosse,
  • Peter Küster,
  • Birte KinderHolger Köster,
  • Susanne Büsing,
  • Margarethe Pohl,
  • Carsten Schwarz,
  • Andreas Artlich,
  • Alexander Kiefer,
  • Manfred Ballmann,
  • Nikola Gjorgjevski,
  • Markus A. Rose,
  • Friederike Ruf,
  • Rolf Mahlberg,
  • Wolfgang Thomas,
  • Ute Graepler,
  • Sebastian Bode,
  • hilipp Meyn,
  • Josef Rosenecker,
  • Cordula Koerner,
  • Klaus-Michael Keller,
  • Tina Teßmer,
  • Helge Hebestreit,
  • Gerhild Lohse

Journal volume & issue
Vol. 32
p. 100690

Abstract

Read online

Summary: 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 (ppFEV1) 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/m2 (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 ppFEV1 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.

Keywords