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 Registry

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; German CF Registry of the Mukoviszidose e.V. and participating CF sites

doi:10.1016/j.lanepe.2023.100690

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 Registry

Lancet Reg Health Eur. 2023 Jul 28:32:100690. doi: 10.1016/j.lanepe.2023.100690. eCollection 2023 Sep.

Authors

Sivagurunathan Sutharsan¹, Stefanie Dillenhoefer², Matthias Welsner¹, Florian Stehling³, Folke Brinkmann⁴, Manuel Burkhart⁵, Helmut Ellemunter⁶, Anna-Maria Dittrich^{7

8}, Christina Smaczny⁹, Olaf Eickmeier¹⁰, Matthias Kappler¹¹, Carsten Schwarz¹², Sarah Sieber¹³, Susanne Naehrig¹⁴, Lutz Naehrlich^{15

16}; German CF Registry of the Mukoviszidose e.V. and participating CF sites

Collaborators

German CF Registry of the Mukoviszidose e.V. and participating CF sites:
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

Affiliations

¹ Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Adult Cystic Fibrosis Center, University of Duisburg-Essen, Essen, Germany.
² Department of Pediatric Pulmonology, Cystic Fibrosis Center, University Children's Hospital of Ruhr University Bochum at St. Josef-Hospital, Bochum, Germany.
³ Pediatric Pulmonology and Sleep Medicine, Children's University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁴ Department of Pediatric Pneumology & Allergology, The University of Lübeck, University Medical Center Schleswig-Holstein, Campus Centrum Lübeck, Member of Airway Research Center North (ARCN) of the German Center of Lung Research (DZL), Lübeck, Germany.
⁵ Mukoviszidose Institut gGmbH (MI), Bonn, Germany.
⁶ Medical University of Innsbruck, Cystic Fibrosis Centre Innsbruck, Innsbruck, Austria.
⁷ Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
⁸ Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Germany.
⁹ University Hospital Frankfurt/Main, Goethe University, Pneumology and Allergology, Christiane Herzog CF Center Frankfurt/Main, Frankfurt/Main, Germany.
¹⁰ Pediatric Allergology, Pulmonology & Cystic Fibrosis, Christiane Herzog CF Center- Frankfurt a.M., University Hospital Frankfurt a.M., Germany.
¹¹ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Germany.
¹² Division Cystic Fibrosis, HMU-Health and Medical University Potsdam, Clinic Westbrandenburg, Potsdam, Germany.
¹³ STAT-UP Statistical Consulting & Data Science GmbH, Munich, Germany.
¹⁴ Department of Internal Medicine V, Cystic Fibrosis Center for Adults, University Hospital, Ludwig Maximilian University (LMU) Munich, Germany.
¹⁵ Department of Pediatrics, Justus-Liebig-University Giessen, Giessen, Germany.
¹⁶ Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Giessen, Germany.

Abstract

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: Body mass index; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Lung function; Pulmonary exacerbation; Real-world evidence; Sweat chloride.