#NACFC2022 – Trikafta Helps to Resolve Inflammation in CF: Study

Triple combo therapy found to promote lung tissue repair in patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with the triple-combination therapy Trikafta (elexacaftor/tezacaftor/ivacaftor) reduces inflammation and promotes lung tissue repair in cystic fibrosis (CF), new research indicates.

Nicola Robinson, MD, from The University of Edinburgh, presented the findings at the 2022 North American Cystic Fibrosis Conference, in the talk “Elexacaftor/Tezacaftor/Ivacaftor treatment promotes inflammation resolution in people with CF.”

Trikafta contains a combination of three CFTR modulators that can increase the activity of the CFTR protein in people with certain CF-causing mutations. The therapy is approved in the U.S. to treat patients, 6 and older, with eligible mutations.

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Researchers set out to study Trikafta’s effect on lung inflammation

CF is characterized by chronic inflammation in the lungs. While clinical trial data have shown that Trikafta can improve lung function for CF patients, its effect on lung inflammation are not clear. Robinson and colleagues conducted a study to learn more.

The aim was “to determine the impact of CFTR modulator therapy on systemic and pulmonary inflammation in people with CF,” Robinson said.

Blood samples from 103 patients (median age 29) were collected, 56 from males and 47 from females. From the participants with known mutations, 98 had at least one CFTR gene copy with the F508del change — the most common CF-causing mutation. Samples were collected before and up to one year after initiating treatment.

Treatment with [Trikafta] significantly improves systemic markers of inflammation in CF

Results showed that levels of interleukin-6 (IL-6), a molecule implicated in inflammation, decreased significantly within three months of starting on Symdeko (tezacaftor/ivacaftor). Of note, IL-6 was the only cytokine (a type of signaling molecule) with elevated levels in patients at the start of the study, compared to healthy controls.

Levels of IL-6 and C-reactive protein (CRP), an inflammation marker, were significantly reduced at one month with Trikafta, which was sustained through one year of treatment. The analysis also showed the reductions in IL-6 and CRP were correlated.

Levels of the inflammation-related molecule IL-8 and of the anti-inflammatory IL-10 did not change significantly following Trikafta treatment.

Results at one year of Trikafta therapy showed significant reductions in the levels of IL-20 and MMP-10, both implicated in wound healing.

Levels of calprotectin — a risk marker of pulmonary exacerbations (times when lung function suddenly worsens, usually because of an infection) — decreased significantly within one year of starting treatment with Trikafta. A trend toward calprotectin decrease was also seen with Symdeko within one year.

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Results in patients who had not been on a CFTR modulator previously showed rapid drops in calprotectin levels. Calprotectin decreases within three months with Trikafta were similar when comparing the group starting on CFTR modulators to patients who had been on Symdeko before Trikafta.

Ten patients who had not been on a modulator previously underwent lung imaging before starting Trikafta, and then again after one month, three months, and one year. Analyses of these lung images suggested that Trikafta treatment led to reduced wall thickening in the airways and less mucus plugging in all 10 participants.

“Treatment with [Trikafta] significantly improves systemic markers of inflammation in CF,” the scientists wrote.

“Radiological improvements were visible in all those who underwent CT scanning in our cohort following a year of [Trikafta],” they added.

Note: The Cystic Fibrosis News Today team is providing in-depth coverage of the 2022 North American Cystic Fibrosis Conference (NACFC) Nov. 3–5. Go here to see the latest stories from the conference.