#NACFC2021 – Trikafta Shows Little Effect on GI Symptoms Over 6 Months

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Six months of treatment with Trikafta does not substantially alter digestive symptoms in people with cystic fibrosis (CF), new research shows.

“We speculate that [Trikafta], while it may lead to improvement in lung function, may have little or very delayed impact on gastrointestinal symptoms in people with CF,” Sarah Jane Schwarzenberg, MD, a professor of pediatrics at the University of Minnesota, said in a talk at the 2021 North American Cystic Fibrosis Conference, held virtually Nov. 2–5.

Her presentation was titled “Elexacaftor/tezacaftor/ivacaftor alters gastrointestinal symptoms: Six-month report of PROMISE GI.

Many people with CF experience digestive problems, ranging from constipation, to diarrhea, to difficulty getting enough nutrition from food.

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Trikafta is an triple-combination treatment for CF marketed by Vertex Pharmaceuticals. It contains three CFTR modulators, which correct the functionality of the defective CFTR protein in people with specific mutations. While the medication’s ability to improve lung function in eligible patients has been proven in clinical trials, its effects on other CF symptoms, such as digestive problems, are not fully understood.

When Trikafta was first approved in the U.S. in 2019, researchers started an observational study called PROMISE (NCT04038047) to gather more data on the treatment.

“We hoped to better understand the impact of [Trikafta] on gastrointestinal symptoms and health-related quality of life related to GI [gastrointestinal] wellness,” Schwarzenberg said.

She presented data for 302 participants in PROMISE who had completed a number of standardized questionnaires on the severity of digestive symptoms before they started on Trikafta (baseline), and after six months on the therapy.

Of the patients in PROMISE, about half were male, and over 90% were white. The study included participants 12 years or older, and there was a broadly even distribution of adolescents (ages 12–17), young adults (18–29), and adults (30 and older). Just over half had previously been on other kinds of CFTR modulator therapies.

Schwarzenberg presented analyses that compared digestive symptoms before starting treatment and after six months, looking for trends. These analyses were broken down by age and sex.

Overall, “it’s apparent that there has not been an enormous change” in terms of upper digestive symptoms, such as nausea and abdominal pain, Schwarzenberg said.

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The most obvious changes were for bloating, but the change varied by sex: females tended to have less severe bloating after six months on Trikafta, whereas males tended to report worsening bloating. These differences were more pronounced in older patients.

The changes in upper digestive symptoms “overall are fairly small, and it’s unclear whether they have any clinical significance,” Schwarzenberg said.

Similar results were found for lower abdominal symptoms, such as constipation — there was little change over six months on Trikafta.

In terms of digestive health-associated life quality, overall trends showed improvement after six months of therapy. The most substantial effect noted was reduced dissatisfaction in males younger than 18.

However, “the changes here are actually very small,” Schwarzenberg said.

From baseline to six months, the number of patients reporting constipation did not change substantially, while the proportion with diarrhea increased (1.8% to 7.8%). This increase is not statistically significant, but it does line up with anecdotal reports of diarrhea in people starting on Trikafta and other CFTR modulators, according to Schwarzenberg.

In an analysis of 99 patients with available data, levels of fecal calprotectin — a marker of intestinal inflammation — decreased significantly after six months on Trikafta. Decreases in calprotectin were closely associated with decreases in weight, Schwarzenberg noted.

While this association doesn’t necessarily mean there’s a cause-and-effect relationship between calprotectin levels and body weight, Schwarzenberg said this association is “an interesting finding to pursue.”

In addition, there were no changes in levels of fecal elastase (a pancreatic enzyme needed for digestion) or steatocrit — a marker of fat — after six months of Trikafta treatment.

Editor’s note: The Cystic Fibrosis News Today team is providing coverage of the virtual 2021 North American Cystic Fibrosis Conference (NACFC) Nov. 2–5. Go here to see the latest stories from the conference.