Trikafta modestly eases digestive symptoms in children with CF: Study
Triple-combination thearpy does not reverse pancreatic insufficiency
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One year of treatment with Trikafta modestly eased some digestive symptoms and led to fewer reports of constipation in children with cystic fibrosis (CF), although those were already low before the triple-combination therapy, a new study reports.
It also increased the proportion of patients with normal levels of fecal calprotectin, a biomarker of gut inflammation. However, it did not reverse pancreatic insufficiency.
While Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor, significantly improves lung function for people with CF, “similarly significant improvements in gastrointestinal symptoms and function do not seem to occur,” the scientists wrote.
The study, “Impact of elexacaftor/tezacaftor/ivacaftor on gastrointestinal outcomes, inflammation, exocrine pancreatic function and fat malabsorption: Report of PROMISE pediatric substudy,” was published in the Journal of Cystic Fibrosis.
Study looked at Trikafta’s effects on digestive symptoms
CF is caused by mutations in the gene encoding the CFTR protein, resulting in the accumulation of thick, sticky mucus in organs such as the lungs and the digestive tract. Most CF patients have exocrine pancreatic insufficiency (EPI), a condition characterized by insufficient release of pancreatic enzymes that help break down nutrients.
While CFTR modulators, including Trikafta, have shown to improve lung function, less is known regarding their effects on digestive symptoms.
To learn more, researchers analyzed data from the PROMISE study (NCT04613128), which looked at the effects of Trikafta in children with CF and at least one F508del mutation, ages 6 to 11 years. This substudy specifically assessed digestive issues and fecal biomarkers in children who recently started Trikafta.
The study enrolled 124 children, mainly boys (57.3%) and white (96%), with a mean age of 9.2 years. Before Trikafta initiation, about half were taking Orkambi (lumacaftor/ivacaftor) or Symdeko (tezacaftor/ivacaftor), 10.5% were taking Kalydeco (ivacaftor), and 38.7% were not on CFTR modulators.
Digestive symptom frequency and severity were measured using patient-reported outcome measures (PROMs) from three validated symptom questionnaires — PAGI-SYM to evaluate gastrointestinal symptom severity, PAC-SYM to assess constipation, and PAC-QOL to assess the impact of constipation symptoms on patients’ quality of life — and a stool-specific questionnaire.
Overall, there were no significant differences in total scores of any of the PROMs. However, Trikafta eased symptom severity in PAGI-SYM domains of bloating and fullness/early satiety, as well as abdominal symptoms assessed with PAC-SYM.
“Although some of the changes in the PAGI-SYM scores were statistically significant, they are not likely clinically meaningful,” the researchers wrote.
Reports of constipation decreased, but scores were low at baseline
Although most children reported a normal stool pattern before and after Trikafta, results showed fewer reports of a constipated stool pattern within one year of treatment (14.4% before vs. 2.5% after Trikafta).
“Reports of constipation decreased, but those scores were also low at baseline,” the investigators noted.
Fecal calprotectin was elevated in 64% of children and normal in 22% before Trikafta, particularly in those who were not taking CFTR modulators. After six months of treatment, the proportion of children with elevated fecal calprotectin was reduced to 35%, while those with normal levels increased to 40%.
It is possible that a greater effect will be seen after several years of [Trikafta] treatment, but at the present time, close attention to [gastrointestinal] disease is essential for decreasing the burden of symptoms and maintaining overall health of [people with CF].
As assessed by fecal elastase levels lower than 100 micrograms (mcg)/g, results further showed that 73% of the children had EPI before Trikafta. This percentage did not change significantly up to six months of treatment. Likewise, no significant changes were seen in fecal steatocrit, a test used to detect excess fat in the stool and assess fat malabsorption.
Levels of liver enzymes and measures of liver scarring did not change with treatment.
“It is possible that a greater effect will be seen after several years of [Trikafta] treatment, but at the present time, close attention to [gastrointestinal] disease is essential for decreasing the burden of symptoms and maintaining overall health of [people with CF],” the researchers concluded.
