“…years • Respiratory adverse events were reported by 27/51 patients and 16 discontinued treatment • Discontinuation rate was greater than reported in clinical trials Improvement in FEV 1 was observed with continued treatment compared to what was observed in pivotal trials Hatziagorou et al18 2018 years • Common adverse events included infective pulmonary exacerbations, abnormal respiration, cough, and dyspnea• Patients initiating LUM/IVA at half the dose experienced less frequent respiratory events (56% vs. 71%) of shorter median duration (4 vs. 9 days); these patients did not require dose modifications or discontinuation due to adverse respiratory events and were increased to full dose over 2 weeks• CF patients with ppFEV1 < 40% might benefit from initiation at a lower dose and close monitoring before increasing to the full doseWark et al years • Statistically significant improvement in 6MWT at 4 weeks and maintained at 52 weeks, and FEV 1 at 24 weeks and maintained at 52 weeks Tong et al 21 2020 LUM/IVA F508del homozygous LUM/IVA, 72; controls, 33 Mean 31 (SD: 11.6) years • Statistically significant reduction in pulmonary exacerbations requiring IV antibiotics, prolonged time to first exacerbation, and reduced rate of decline in ppFEV 1 over 12 months • Chest tightness and dyspnea were experienced by 55% of patients and 32% ceased treatment over the 12 month observation period Ejiofor et aland 3rd quartile) 33.0 (23−40) years • Statistically significant improvement in ppFEV 1 after 3, 6, 9, and 12 months (in comparison to baseline), cardiopulmonary exercise test, and health-6 (SD: 8.6) years • Statistically significant reduction in the number of pulmonary exacerbations requiring hospitalization, hospitalization days, IV antibiotic usage days, increase in FEV 1, and body weight Martin et al 24 2021 ELE/TEZ/IVA F508del homozygous (N = 39), F508del/other (N = 61), Unreported (N = 1) 101 28−41 years • Patients reported significant impact on respiratory symptoms, quality, general well-being, physical selfesteem, and reduction in treatment burden after initiation of ELE/TEZ/IVA O'Shea et al 25 2021 ELE/TEZ/IVA F508del homozygous (N = 8), chloride concentrations, and infective exacerbations requiring hospitalization • No therapy related significant adverse effects were observed Carnovale et al 26 2021 ELE/TEZ/IVA F508del/minimal function mutation 46 17−52.6 years • Statistically significant improvement in mean sweat chloride concentrations, ppFEV 1 after 1 and 6 months of therapy, BMI, and quality of life • No adverse effects were observed Burgel et al 27 2021 ELE/TEZ/IVA At least one F508del mutation 245 24−38 years • Statistically significant improvement in mean ppFEV 1 , BMI, long-term oxygen, noninvasive ventilation, and/or enteral tube feeding • Twofold decrease in the number of lung transplantations over a 2 year period primarily due to the rapid disease modification effects of ELE/TEZ/IVA Kos et al 28 2022 ELE/TEZ/IVA F508del heterozygous (N = 8), Statistically significant improvement in ppFEV1 and BMI • ELE/TEZ/IVA was well tolerated with mild side effects and led to a self-reported improvement in quality of life as well as reduction in pulmonary exacerbations and hospitalizations • Pulmonary and extrapulmonary benefits were maintained for 12 months McCoy et al 29 2023 ELE/TEZ/IVA F508del homozygous (N = 8), F508del heterozygous (N = 10) 18 15−49 years • Over a period of 2 years, statistically significant improvement in ppFEV1, body weight, BMI, and sweat chloride concentrations were observed • Treatment was well tolerated by all patients with no treatment discontinuations, deaths, or need for lung transplant after 2 years publication separated outcomes by age (pediatric vs. adult), likely due to the small proportion (e.g., 1 of 13 pwCF) of the total population. 15,28 The data regarding safety and efficacy outcomes of CFTR modulators in pwCF and severe lung disease is limited.…”