Estimated Event Rate Per Patient Year
1.2 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0
0.98
Pulmonary Exacerbations
FIGURE 3B: All Pulmonary Exacerbations
Rate Ratio, 0.37; 95 % CI, 0.25-0.55 P < 0.001
0.37
Placebo
0.24
Pulmonary Exacerbations Leading to Hospitalization
Elexacaftor-tezacaftor-ivacaftor
Pulmonary Exacerbations Treated with Intravenous Antibiotics
Statistically significant reduction in pulmonary exacerbations post-treatment with ETI when compared to placebo. 35 Figure obtained from“ Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele”“ The Changing Epidemiology of Cystic Fibrosis: The Implications of Adult Care.” From [ NEJM, Middleton et al, Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele, Volume No. 381, Page 1809-1819. Copyright 2019 Massachusetts Medical Society. Figure reprinted with permission from Massachusetts Medical Society.
is $ 54,000 and nearly 6 % of individuals are without health insurance. 39 Although life-changing for many, ETI is not without side effects. Upper respiratory tract infection is the most common, found in 16 % of cases, whereas diarrhea and gastrointestinal distress are second, found in 14 % of cases. 40
It is important to remember 10 % of patients diagnosed with CF are not eligible for current modulators due to genotype. 41 Gene therapy may prove a future therapeutic option for those unresponsive to CFTR modulator therapy. 41 Clinical trials have explored gene therapy using an adenovirus vector with delivery to the nasal endothelium; however, clinical efficacy is limited likely due to the rapidly replicating epithelium. 41 Future studies should explore the progression of gene therapy. 41
Rate Ratio, 0.29; 95 % CI, 0.14-0.61
0.07
0.36
Rate Ratio, 0.22; 95 % CI, 0.11-0.43
0.08
Prior to highly effective CFTR modulators, lung transplantation was a common therapeutic option for those with advanced lung disease refractory to medical therapy. 42 Specific criteria must be met for lung transplantation for those with CF. 43 For those younger than 18 years old, transplant is recommended when forced expiratory volume in FEV1 is less than 50 % with a rapid decline in the past year, FEV1 is less than 50 % with evidence of decreased survival, or FEV1 is less than 40 %. 43 For those older than 18 years old, initiation of transplant referral is recommended when FEV1 is less than 50 % with evidence of rapid decline in the past year, FEV1 is less than 40 % with evidence of decreased survival, or FEV1 is less than 30 %. 43 Studies have found those with CF have longer medial survival time post-transplant compared to those who undergo lung transplant for other indi-
cations( 8.3 years vs. 5.7 years), along with an increased probability of survival post-transplant compared to other disease states. 42 This may be due to younger age at transplant, and lifelong experience managing a complicated treatment regimen. Effective CFTR modulator therapy may play a role in reducing the number of annual lung transplants. 44 Presented in 2024 at the 47th European Cystic Fibrosis Conference, interim analysis of a five-year study performed demonstrated an 86 % reduction in lung transplants in the US and 96 % reduction in Germany after initiation of ETI. 44 Other benefits included a reduction in CF exacerbations and death rate. 44 Furthermore, CFTR modulator therapy is also being explored for effectiveness post-lung transplant. 45 ETI pharmacotherapy post-lung transplantation in a single center study yielded improvements in extrapulmonary manifestations of CF. 45 Continued effective modulator therapy will likely play a key role in reducing future lung transplants and extrapulmonary symptoms.
West Virginians are faced with various barriers to healthcare delivery, and lung transplantation is no different. Currently, WV is without a lung transplant center and studies have found mortality correlates to transplant wait-time. 46 Factors associated with transplant delay in rural populations include lack of transportation, insurance coverage, delay from initial referral, and financial difficulties. 46 These factors should be considered when evaluating rural populations for transplant.
SUMMARY
To date, there is no cure for CF, but significant advancements in the management of CF have been made. Treating a disease starts with identification, and early diagnosis of CF has been shown to increase survivability. 47 Currently, 90 % of patients living with CF respond to CFTR modulator therapy. However, for those unable to tolerate modulator therapy or for the 10 % ineligible, further research is needed and gene therapy may prove invaluable. 41 WV’ s unique geography provides challenges for both patients and providers and the Mountain State CF Center seeks to provide solutions.
16 • www. wvsma. org