Trikafta (elexacaftor/tezacaftor/ivacaftor) / Vertex - LARVOL DELTA

People with cystic fibrosis with high sputum neutrophil elastase on elexacaftor-tezacaftor-ivacaftor exhibit worse pulmonary function and pro-inflammatory airway milieu. (PubMed, Sci Rep) - "These findings suggest pwCF on ETI who have high airway NE activity also have high inflammatory burden and a history of lower pulmonary function. Adjunctive neutrophil-targeted interventions may be beneficial for these individuals to receive maximal benefits from ETI therapy."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • ELANE • IL1B • IL6 • TNFA

Comparative efficacy and safety of CFTR modulators for people with cystic fibrosis with phe508del mutation: a systematic review and bayesian network meta-analysis. (PubMed, EClinicalMedicine) - "Our findings indicate that vanzacaftor-tezacaftor-deutivacaftor and elexacaftor-tezacaftor-deutivacaftor emerged as the most effective treatment options in adults. However, these results should be interpreted cautiously due to limited data and the low quality of existing evidence. None."

Journal • Retrospective data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

CFTR Modulator Response in Nasal Organoids Derived from People with Cystic Fibrosis. (PubMed, Cells) - "Despite the progressive extension of CFTR variant eligibility to the triple combination of elexacaftor/tezacaftor/ivacaftor (ETI), most rare CFTR pathogenic variants remain ineligible for CFTR modulators...These results suggest that the nasal organoid FIS assay, pending confirmation of the prediction in the corresponding pwCF, might be considered as a powerful in vitro tool to predict modulator efficacy in each pwCF, guiding out-of-label prescription in CF, and to identify uncharacterized variants responsive to modulators. This approach may allow comparison of the efficacy of different therapeutics or the identification of innovative strategies for non-responding genotypes, improving personalized therapy and quality of life for pwCF."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Elexacaftor/tezacaftor/ivacaftor corrects salt-wasting in cystic fibrosis. (PubMed, J Cyst Fibros) - "In pwCF, ETI treatment improves NaCl and fluid conservation. Future guidelines should consider an increased risk for cardiovascular disease in pwCF after initiation of CFTR modulator treatment. Salt repletion appears unnecessary in ETI-treated pwCF."

Journal • Cardiovascular • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Heterogeneity of short-term elexacaftor-tezacaftor-ivacaftor response in cystic fibrosis using 129Xe MRI. (PubMed, Thorax) - "Though all outcome measures showed a positive response, response to ETI was heterogeneous between individuals and between 129XeMRI, MBW and spirometry. Leveraging the rich information provided by multimodal tools will be critical to understanding the nature of CF lung disease and measuring response to future therapies in the era of CFTR modulators."

Heterogeneity • Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapies on Liver Transplant Outcomes. (PubMed, Gastro Hep Adv) - "Food and Drug Administration (FDA) approval of CFTR modulators: ivacaftor (January 31, 2012; single therapy), ivacaftor-lumacaftor (July 2, 2015; dual therapy), and ivacaftor-tezacaftor-elexacaftor (October 21, 2019; triple therapy). There were no significant differences in post-LT survival pre- and post-FDA approval of single, dual, or triple CFTR therapy. These findings suggest that CFTR modulators may mitigate CFrLD complications and delay the need for waitlisting as physicians await the patient's response to therapy and reassess the need for LT."

Journal • Cystic Fibrosis • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation • CFTR

Lung Function Assessment of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Cystic Fibrosis Patients With Ventilation/Perfusion SPECT/CT. (PubMed, Clin Nucl Med) - "The third patient exhibited no scintigraphic improvement, consistent with no clinical benefit. These results suggest that, while CT reflects structural changes, V/Q SPECT/CT provides complementary information on regional lung function, enabling early detection of ETI response."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Cooling the flames, clearing the airways: systemic inflammation in the era of elexacaftor/tezacaftor/ivacaftor. (PubMed, Eur Respir J) - No abstract available

Journal • Inflammation

Real-World Impact of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Italy: A Retrospective Study from a Cystic Fibrosis Center. (PubMed, Pulm Ther) - "Substantial improvements in lung function and reductions in HCRU were observed after treatment with ELX/TEZ/IVA in the Verona CF Center. Results contribute to the growing evidence of country-specific real-world data on the positive impact of ELX/TEZ/IVA."

Journal • Real-world evidence • Retrospective data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Elexacaftor-Tezacaftor-Ivacaftor Reduces Revision Sinus Surgery in People With Cystic Fibrosis. (PubMed, Laryngoscope) - "ETI was associated with a significant decrease in the frequency and rate of ESS in pwCF. These findings suggest an improvement in CF-related chronic rhinosinusitis outcomes following ETI and may influence future CF treatment decisions."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • Sinusitis

Impact of Elexacaftor/Tezacaftor/Ivacaftor (ETI) Treatment on Clinical Outcomes in a Single Centre Cohort of Paediatric Patients With Cystic Fibrosis. (PubMed, J Paediatr Child Health) - No abstract available

Clinical data • Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pediatrics • Pulmonary Disease • Respiratory Diseases

Home sputum collection for Aspergillus fumigatus detection in adults with cystic fibrosis. (PubMed, ERJ Open Res) - "Elexacaftor/tezacaftor/ivacaftor (ETI) has impacted the ability for people with cystic fibrosis (PwCF) to spontaneously expectorate sputum, leading to lower respiratory sampling rates and infection detection challenges...Af was detected in remotely collected sputum samples. Further work to assess the validity of home sputum samples in PwCF is necessary to determine the value of remote specimens in clinical and research settings."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

3D Automated Segmentation of Bronchial Abnormalities on Ultrashort Echo Time MRI: A Quantitative MR Outcome in Cystic Fibrosis. (PubMed, J Magn Reson Imaging) - "RiSeNet may enable semantic segmentation of CF abnormalities on radiation-free UTE-MRI."

Journal • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Body Image Perceptions and Elexacaftor/Tezacaftor/Ivacaftor (ETI) Use in Adolescents and Young Adults Living With Cystic Fibrosis. (PubMed, Pediatr Pulmonol) - "This cross-sectional, single-site study explored the relationship between body image concerns for AYAwCF since the approval of ETI and their relationship to adherence. Results help identify areas for intervention."

Journal • Retrospective data • CNS Disorders • Cystic Fibrosis • Depression • Genetic Disorders • Immunology • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

Antisense oligonucleotide targeting the E3 ligase RFFL potentiates CFTR modulator efficacy in CF primary bronchial epithelial cells. (PubMed, Mol Ther Nucleic Acids) - "Although CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) provide clinical benefit, their efficacy is limited, particularly in patients with rare or poorly responsive CFTR mutations...In some cases, the ASO alone restored CFTR levels to those achieved by ETI treatment. These findings establish RFFL-targeting ASOs as first-in-class CFTR stabilizers and highlight their potential as a nucleic acid-based therapeutic strategy for CF caused by both common and rare CFTR mutations."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • CFTR

Differences in pulmonary exacerbation risks among CF subpopulations. (PubMed, J Cyst Fibros) - "Prior-year PEx frequency (treated by any route) was strongly associated with future PEx risk independent of modulator use. Although ETI reduces PEx rates, agents intended to further reduce rates can be studied in pwCF receiving ETI having experienced higher numbers of prior-year PEx."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Elexacaftor/tezacaftor/ivacaftor is associated with long-term reduction in use of chronic respiratory therapies in cystic fibrosis. (PubMed, J Cyst Fibros) - "ETI was associated with long-term reductions in use of chronic respiratory therapies (inhaled antibiotics, hypertonic saline, dornase alfa, azithromycin) among pwCF ≥6 years, indicating a sustained decrease in respiratory treatment burden among those on ETI therapy."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Pharmacokinetic assessment of elexacaftor/tezacaftor/ivacaftor and their metabolites in maternal blood, cord blood, the neonate, and breastmilk of a cystic fibrosis carrier mother/affected fetus dyad. (PubMed, J Cyst Fibros) - "IVA-M1 and IV-M6 concentrations were lower at 1 and 4 weeks relative to delivery. To our knowledge, this is the first report of ETI metabolite concentrations following in utero administration."

Journal • PK/PD data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Impact of elexacaftor/tezacaftor/ivacaftor on clinical outcomes and quality of life in children with cystic fibrosis aged 6–11 years in the real-world setting (BTS WM 2025) - "The remaining elements were scored as of lower relevance, with less than 20% of participants voting for them. Conclusions This initial DELPHI round to develop best practice standards for CYP with Asthma identified patient red flags as the most important core element of the discharge letter; further rounds are required to reach consensus on the other elements, which will inform the outline of the discharge letter template."

Clinical • Clinical data • HEOR • Real-world • Real-world evidence • Asthma • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • NRAP

Determinants of tidal volume in Nepali infants less than 6 weeks of age: a cross-sectional study (BTS WM 2025) - "Results MBW in the group aged 2–5 years with CF has allowed the clinical team to measure the response to Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy using pre and post LCI in a patient group who were previously modulator naive...In both groups trend data is used to find out if there is an improvement or decline in LCI. Download figure Open in new tab Download powerpoint Abstract P134 Figure 1 Annual test service data Conclusion The introduction of the LCI service clinically has allowed earlier access to diagnostic testing, treatment monitoring, treatment intervention and reduction in treatment burden, which previously would not have been possible."

Observational data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Clinical characteristics of a combined adult and paediatric cohort of patients with primary ciliary dyskinesia (BTS WM 2025) - "Introduction The TRAJECTORY Study, an ongoing real-world observational study, previously showed that elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves clinical outcomes and quality of life (QoL) in people with CF aged ≥12 years...Domains with the most improvement observed in mean (SD) change for parents/caregivers were Weight (14.3 [36.0]), Respiratory Symptoms (11.7 [20.6]), Digestive Symptoms (10.0 [8.9]), Eating Problems (9.4 [25.6]), and Treatment Burden (9.4 [21.0]) ( table 1 ); consistent improvements were reported for children ages 6–11 in all domains. View this table: View inline View popup Download powerpoint Abstract P133 Table 1 Summary of Mean CFQ-R Domains at Baseline and Change from Baseline Conclusions ELX/TEZ/IVA treatment showed improvement in function and nutritional status, and respiratory and non-respiratory CFQ-R domains for children aged 6–11 years after 12 months of treatment."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Otorhinolaryngology • Pediatrics • Respiratory Diseases

Long-term effects of elexacaftor/tezacaftor/ivacaftor on clinical outcomes and quality of life among adolescents and adults aged 12+ with cystic fibrosis: Interim results from the TRAJECTORY Study (BTS WM 2025) - "The largest domain increases in mean (SD) absolute change from baseline at 36 months were Respiratory Symptoms (26.3 [19.3]), Health Perceptions (15.3 [18.3]), Physical Functioning (12.2 [19.6]), School Functioning (+12.0 [16.2]), Vitality (9.7 [17.6]) and Treatment Burden (9.1 [14.4]) ( table 1 ). View this table: View inline View popup Abstract S68 Table 1 Summary of Mean CFQ-R Domains at Baseline and Change from Baseline Conclusions ELX/TEZ/IVA treatment showed substantial benefits in clinical outcomes and QoL in the real-world setting with sustained improvement up to at least 36 months for PwCF aged ≥12 years."

Clinical • Clinical data • HEOR • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Pre-conception lung function and the pregnancy outcomes among females with cystic fibrosis (fwCF) in the CF-transmembrane conductance regulator modulator (CFTRm) era (BTS WM 2025) - "Introduction Since widespread availability of highly effective CFTRm elexacaftor/tezacaftor/ivacaftor, pregancy rates have doubled among fwCF in the UK...BJOG . 2020 Dec 16; 127 (13):1696–703."

Cardiovascular • Cystic Fibrosis • Genetic Disorders • Immunology • Infertility • Obstetrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Reduction in serum markers of inflammation in people with cystic fibrosis who are chronically infected with pseudomonas aeruginosa is seen after treatment with Elexacaftor/Tezacaftor/Ivacaftor (BTS WM 2025) - "Those with a >10% improvement in ppFEV 1 experienced greater reduction in neutrophil count, suggesting an association between change in systemic inflammation and airway health on ETI. Post-ETI inflammatory change and its impact warrants further exploration."

Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Respiratory Diseases • CRP

Delayed-onset drug-induced liver injury in a cystic fibrosis patient on long-term elexacaftor/ivacaftor/tezacaftor therapy: A case report and literature review. (PubMed, Can Liver J) - "Using the Roussel Uclaf Causality Assessment Method (RUCAM), a score of 8 indicated a probable link to drug-induced liver injury (DILI), which was further supported by World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment. This case highlights the potential for delayed-onset hepatotoxicity with ETI and emphasizes the need for continued liver monitoring during long-term therapy."

Journal • Cystic Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Failure • Pulmonary Disease • Respiratory Diseases • Thrombosis • CFTR