North American Cystic Fibrosis Conference

North American Cystic Fibrosis Conference

Source:

Bermingham B, et al. Poster-645. Presented at: North American Cystic Fibrosis Conference; Oct. 20-23, 2020 (virtual meeting).

Disclosures: Bermingham reports no relevant financial disclosures.
November 06, 2020
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Triple therapy improves FEV1 in patients with cystic fibrosis, advanced lung disease

Source:

Bermingham B, et al. Poster-645. Presented at: North American Cystic Fibrosis Conference; Oct. 20-23, 2020 (virtual meeting).

Disclosures: Bermingham reports no relevant financial disclosures.
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Triple combination therapy with elexacaftor/ivacaftor/tezacaftor improved FEV1 in patients with cystic fibrosis and pre-existing advanced lung disease, according to results of a retrospective analysis.

The triple combination therapy, elexacaftor/ivacaftor/tezacaftor (Trikafta, Vertex Pharmaceuticals), was approved in 2019 for treatment of cystic fibrosis in patients aged at least 12 years with one or more F508del mutations in the CFTR gene.

Lungs and bronchi
Source: Adobe Stock.

“Despite patients with advanced lung disease being excluded from phase 3 trials, patients with advanced lung disease are receiving therapy with unknown clinical efficacy and safety profile,” Brent Bermingham, MD, pulmonary and critical care fellow at the Medical University of South Carolina, Charleston, said during a presentation at the virtual North American Cystic Fibrosis Conference. “If effective, treatment with triple combination therapy could alter the need and timing for lung transplantation referral.”

The current study aimed to characterize the short-term clinical efficacy, safety and implications for transplant referral in patients with pre-existing advanced lung disease who received triple therapy.

The multicenter, retrospective cohort study included 60 adults (mean age, 31.9 years; 50% women) with cystic fibrosis and pre-existing advanced lung disease from three academic centers in the Southeastern U.S. that participated in the Cystic Fibrosis Foundation regional dissemination quality improvement initiative. Patients had an FEV1 less than 40% predicted and high-risk features. Patients were started on triple therapy following FDA approval; 10 patients (mean age, 32.4 years; 30% women) were deemed genetically ineligible and were considered controls.

Baseline FEV1 was defined as the most recent spirometry before therapy initiation and outside of an acute exacerbation; follow-up spirometry was obtained 2 to 3 weeks after initiation of therapy. Baseline FEV1 in the control group was defined as most recent spirometry before FDA approval, and follow-up spirometry was obtained 12 weeks later.

Bermingham reported a 7.8% statistically significant improvement in FEV1 among patients who received triple therapy compared with controls, from31% to 39.6% predicted (P < .0001). There was no improvement in lung function in the control group, which suggests patients with higher lung function at baseline experienced greater improvement after triple combination therapy, Bermingham said.

Based on the 2019 cystic fibrosis lung transplant guidelines that recommend lung transplant discussion as cystic fibrosis lung disease progresses and lung function decreases to below 50% predicted, 40 (66%) patients in the treatment group met the indication for lung transplant referral at the start of triple combination therapy compared with 50% of patients in the control group. In response to therapy, patients with an indication for transplant referral decreased by 20, with more patients meeting the indication for transplant discussion but not referral, and seven patients improved to no indication for transplant discussion, Bermingham said. Researchers observed no improvement in the control group.

Adverse events among patients in the triple therapy group were rare. One discontinuation was reported after lung transplant, which the researchers noted was not related to triple combination therapy.

There are several areas of future research, according to Bermingham, including measuring longer-term spirometry, additional safety data and registry analysis to determine whether treatment is effecting disease trajectory and eventual need for lung transplantation in patients with cystic fibrosis.