New cystic fibrosis transmembrane modulator [CFTR] therapies may be of resurgent benefit for some cystic fibrosis patients, even those with advanced disease.

 Triple therapy in patients with cystic fibrosis with advanced lung disease appears to improve lung function and may delay the need for lung transplantation, according to a multicenter analysis of patients receiving elexacaftor, tezacaftor and ivacaftor.

 Study participants had an expected forced expiratory volume percentage in 1 second (ppFEV1) of 40% or less, or other high-risk factors. The researchers compared them to control patients who were genetically ineligible for triple therapy.

Previous studies of such patients who had previously received single or combination drugs showed an increase in lung function in patients with advanced disease, although the extent of improvement varied from regimen to regimen.

The rationale for our study was that although patients with advanced lung disease were excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they were receiving clinically effective therapy and whose safety profile is not known,”said Bermingham, a lung specialist.

The lung transplant guidelines recommend that clinicians begin discussing the potential benefits of lung transplantation when FEV1 falls below 50% of predicted value. Patients should be referred for transplantation when the value is less than 50% and decreases rapidly (> 20 cline in the last 12 months), when it falls below 40% with shortened predictors of survival, or when it falls below 30%. Guidelines were published prior to the approval of triple therapy.

 Researchers conducted a retrospective open-label analysis of 60 patients who started triple combination therapy between September 2019 and February 2020 in three centers in the South East. They compared the percentage of predicted ppFEV1 values ​​before the start of treatment with the ppFEV1 values ​​obtained 212 weeks after the start of treatment. The treated patients were compared to 10 genetically ineligible patients. The two groups were generally similar apart from genetic status, although 100% of the treatment group had pancreatic insufficiency, compared to 90% of controls (P = 0.013).

 The treatment group saw a 7.8% increase in ppFEV1 after starting treatment (P <0.001), compared to 0.5% in the control group (P = 0.65). Prior to the start of treatment, 33% of the treatment group met the criteria to initiate a transplant discussion, while 67% had received a transplant recommendation. After treatment, 55% met the criteria for discussion, 33% were recommended for transplantation and 12% no longer met the criteria for discussion regarding transplantation. Fifty percent of checks are under discussion, and that number drops to 40%, while 50% are referred for transplantation, and that number rises to 60%. In terms of treatment, transplant candidates had increased compulsive survival from 48.9 to 59.16 (P <0.001).

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With Regards,
Andrina Williams
Journal of Cardiac and Pulmonary Rehabilitation