Weight gain linked to lower inflammation in children with CF
Trikafta study finds association emerged early and persisted through 1 year
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For children with cystic fibrosis (CF) who are taking Trikafta (elexacaftor/tezacaftor/ivacaftor), weight gain was associated with decreasing levels of inflammation in the body, a Swiss study reports.
The association was seen in both short- and long-term analyses after treatment began. Changes in inflammation and body mass index (BMI), a measure based on weight and height, were evident within one to two weeks of starting Trikafta. BMI improvements were maintained through a year on the therapy, while markers of inflammation were lower at one year than before treatment.
“Our findings suggest that both early and long-term BMI increase following [Trikafta] initiation in children with CF is associated with a reduction in both systemic [body-wide] and intestinal inflammation,” the team concluded.
The study, “Weight Gain is Associated with Reduced Inflammation in Children with Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor,” was published in Respiratory Medicine.
Trikafta targets faulty CFTR protein
Mutations in the CFTR gene, which contains the blueprint to make the CFTR protein, cause CF. These mutations affect the production or function of CFTR, which normally helps regulate how water and salt move through cells. Without enough working CFTR, people with CF develop thick, sticky mucus that contributes to a variety of symptoms.
Trikafta, marketed by Vertex Pharmaceuticals, is a CFTR modulator that aims to improve how the CFTR protein works in people with eligible mutations. Among the many benefits of Trikafta treatment reported in clinical trials and real-world studies, the combination therapy has been shown to increase weight and reduce inflammation. However, “significant gaps remain in our understanding of the underlying mechanisms driving this overall nutritional improvement,” the researchers wrote.
To investigate this question, they recruited 59 children and adolescents with CF who were beginning treatment with Trikafta. Their median age was 12, and about three-quarters hadn’t previously used CFTR modulators.
“By focusing exclusively on children and adolescents aged 6–17 years, our study addresses a critical knowledge gap concerning CFTR modulators in this age group, where nutritional and growth considerations are paramount,” the researchers wrote.
They used a metric called a Z-score to compare participants’ BMI with others of a similar age. Before starting treatment, the median BMI Z-score was -0.4, meaning participants’ BMI was slightly below the reference median for their age. Most participants were within a normal BMI range, but 5% were underweight.
One to two weeks after starting Trikafta, the median BMI Z-score had increased to -0.3. Most of the increase in BMI Z-score occurred during this early period. After a year of treatment, the median BMI Z-score was -0.2, still significantly higher than before treatment began. Similar trends emerged when the researchers looked at participants’ weight.
Tracking changes in inflammation
In addition to BMI, the team examined several disease-related metrics, including markers of inflammation. From blood tests, they measured levels of leukocytes, or white blood cells, as a marker of systemic inflammation. Through stool tests, they also measured levels of calprotectin, a marker of inflammation in the intestines.
Both blood leukocytes and fecal calprotectin decreased after Trikafta treatment began, suggesting that the therapy was associated with reductions in both systemic and intestinal inflammation.
Between the start of treatment and the short-term, one- to two-week follow-up, decreases in leukocytes were associated with increases in BMI Z-score. “While these associations are modest, they remain consistent across both short- and long-term follow up,” the team emphasized. In the long-term analysis, decreases in calprotectin were similarly associated with increases in BMI Z-score.
“Our results report an association between changes in inflammatory status and improvements in BMI, offering new insights and perspectives into the intricate nature of BMI increase in patients treated with [Trikafta],” the researchers wrote.
However, the study also had limitations, the team noted. For instance, BMI does not fully capture body composition, and the study did not have a control group for comparisons. “Further studies are warranted to better understand the inflammatory pathways modified by [Trikafta] and their long-term relationship with the disease,” the investigators wrote. The researchers also called for studies in larger groups of participants.
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