Clinical efficacy of elexacaftor-tezacaftor-ivacaftor in two siblings with homozygous I1234V mutation cystic fibrosis: A prospective case series
Background: The missense CFTR variant I1234V (c.3700A > G) produces class II protein-folding defects and is prevalent in the Middle East, yet clinical evidence for elexacaftor/tezacaftor/ivacaftor (ETI) in homozygous carriers is sparse. We prospectively evaluated ETI efficacy and safety in two pa...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
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| Series: | Respiratory Medicine Case Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213007125001005 |
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| Summary: | Background: The missense CFTR variant I1234V (c.3700A > G) produces class II protein-folding defects and is prevalent in the Middle East, yet clinical evidence for elexacaftor/tezacaftor/ivacaftor (ETI) in homozygous carriers is sparse. We prospectively evaluated ETI efficacy and safety in two paediatric siblings with homozygous I1234V cystic fibrosis (CF). Methods: A single-centre, prospective case series was undertaken at King Fahad Medical City. Baseline assessments included spirometry, body-mass index (BMI), sputum microbiology, liver biochemistry and high-resolution chest CT. ETI was initiated according to weight-based dosing and patients were reviewed at 6 and 8 months. Primary outcomes were change in percent-predicted forced expiratory volume in 1 second (ppFEV1) and BMI; secondary outcomes were Pseudomonas aeruginosa status, radiological changes and adverse events. Results: After eight months of ETI, ppFEV1 increased from 36 % to 46 % in the 11-year-old girl and from 57 % to 73 % in the 9-year-old boy. Corresponding BMI rose from 11.71 kg/m2 (z = −4.37) to 15.48 kg/m2 (z = −1.22) and from 12.69 kg/m2 (z = −3.12) to 15.74 kg/m2 (z = −0.55), respectively. Chronic P. aeruginosa was eradicated in both patients. Chest CT demonstrated reduced mucus plugging and peribronchial wall thickening with partial regression of cystic bronchiectasis. Conclusions: ETI produced clinically meaningful improvements in lung function, nutritional status, microbiological clearance and radiological appearance in two children homozygous for the rare I1234V mutation. These real-world findings support extending ETI access to patients with rare class II CFTR variants and justify larger multicentre studies to confirm efficacy and long-term safety. |
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| ISSN: | 2213-0071 |