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Observational Study
. 2025 Jul;24(4):716-723.
doi: 10.1016/j.jcf.2025.04.012. Epub 2025 May 15.

LONGITUDE: An observational study of the long-term effectiveness of elexacaftor/tezacaftor/ivacaftor in people aged ≥12 years with cystic fibrosis using data from the United Kingdom Cystic Fibrosis Registry - 2-year analysis

Gabriela Vega-Hernandez  1 , Gordon MacGregor  2 , Andrew Wilfin  3 , Francis Adams  4 , Ciarán Haugh  5 , Carl A Baxter  6 , Heike Wöhling  7 , Sarah L Clarke  8 , Susan C Charman  9 , Siobhán B Carr  10
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Free article
Observational Study

LONGITUDE: An observational study of the long-term effectiveness of elexacaftor/tezacaftor/ivacaftor in people aged ≥12 years with cystic fibrosis using data from the United Kingdom Cystic Fibrosis Registry - 2-year analysis

Gabriela Vega-Hernandez et al. J Cyst Fibros. 2025 Jul.
Free article

Abstract

Background: The cystic fibrosis (CF) transmembrane conductance regulator modulator (CFTRm) elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has demonstrated efficacy and safety in clinical trials and emerging observational studies in people with CF. This study evaluated the real-world impact of ELX/TEZ/IVA in a large cohort of people with CF in the UK.

Methods: LONGITUDE is an observational, registry-based cohort study using data from the UK CF Registry to evaluate outcomes of ELX/TEZ/IVA in people aged ≥6 years who initiated ELX/TEZ/IVA from August 2019. Key outcomes included percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), lung infections, transplants, deaths, and treatment discontinuation. We report results of people ≥12 years with data up to December 31, 2022.

Results: A total of 5187 people were included (mean follow-up 19.1 months). ppFEV1 improvements were observed at 2 years (10.2; 95 % CI: 9.6, 10.8; n = 1448). A clinically meaningful difference in the annual change of ppFEV1 between ELX/TEZ/IVA-treated people and historical CFTRm-naïve controls was observed, with those treated with ELX/TEZ/IVA having less of a decline in lung function over time by 1.1 percentage points (95 % CI: 0.9, 1.4). A 64.7 % reduction in the rate of PEx, increase in BMI by 1.7 kg/m2 (SD: 2.3), reduced lung infections, and low number of lung transplants and deaths were also observed.

Conclusions: People with CF aged ≥12 years in the UK who initiated ELX/TEZ/IVA had sustained improvements in multiple CF-related health outcomes, consistent with results from clinical trials. These results support the positive impact of ELX/TEZ/IVA on the lives of people with CF.

Keywords: Cystic fibrosis; Elexacaftor; Ivacaftor; Real-world; Registry; Tezacaftor.

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Conflict of interest statement

Declaration of competing interest All authors received nonfinancial support (assistance with manuscript preparation) from Nucleus Global, which received funding from Vertex Pharmaceuticals Incorporated. GVH, AW, CAB and HW are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in the company. FA, SLC, SCC, and CH received funding to their institution from Vertex Pharmaceuticals Incorporated per the Data Collection Agreement between Vertex Pharmaceuticals and Cystic Fibrosis Services Ltd (CFSL); CFSL provided data capture, statistical analysis, and reporting preparation in accordance with the agreed protocol and analysis plan developed in collaboration between Vertex and the UK Cystic Fibrosis Registry. SBC received speaker honoraria and other fees from Chiesi Pharmaceuticals; her institution (Royal Brompton Hospital) received honoraria and fees for consultancy, advisory boards, and expert testimony from Vertex Pharmaceuticals, Pharmaxis, Profile Pharma, and the Cystic Fibrosis Trust. GM collaborated on clinical research trials with Vertex and has participated in Vertex advisory board meetings.

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