Discussion
Gaining and maintaining an appropriate weight has traditionally been a challenge for patients with CF. Malnourishment and underweight correlate with reduced lung function, the main contributor to death in CF patients. As a result, the CFF created guidelines on nutrition and growth to address inadequate weight and malnutrition. TCT showed great promise during clinical trials in boosting weight gain and resolving malnutrition; however, long-term data is necessary to understand its long-term effects better.
This study was a retrospective chart review that analyzed how BMI and BMI percentile changed over a year of TCT therapy in patients at our CF center. The results showed that, on average, TCT leads to a significant increase in BMI and BMI percentile in adult and pediatric patients, respectively. Our study included a heterogeneous group of CF patients followed at the University of Iowa Cystic Fibrosis Center, including those with significant lung disease and other conditions that may have been excluded from the trials. Additionally, we describe the modulator effect on weight over a more extended period than previously reported.
In order to better identify other variables that may play a role in weight gain, several subgroups were studied. In the adult population, male and female patients had a similar increase in weight with almost the same average increase in BMI. Surprisingly, the male and female pediatric groups experienced very different changes in BMI percentile after a year on TCT. While the female pediatric group only saw an average increase of BMI percentile of 1.13 percentile, male participants had a much higher increase in BMI percentile at 13.59 in comparison. These results suggest that some gender-specific differences in the young adult population need to be further explored
In the adult population, patients with the homozygous and heterozygous F508del genotypes had a similar average increase in BMI. In contrast, the homozygous F508del had a slightly higher increase in BMI percentile compared to the heterozygous genotype population.
Patients with more severe lung disease in the adult population had a more pronounced increase in their BMI. Patients with moderate lung disease saw the most significant change in BMI percentile in the pediatric population, followed by normal lung function. Patients with mild lung disease saw the most negligible benefit.
Finally, adult patients who were previously on tezacaftor/ivacaftor saw the most significant weight change, followed closely by modulator naïve patients. Patients previously on lumacaftor/ivacaftor experienced less benefit on average, and patients on ivacaftor saw the slightest BMI change. In the pediatric population, modulator naïve children saw the most significant weight change, followed by patients who were previously on lumacaftor/ivacaftor and then patients who were previously on tezacaftor/ivacaftor. The pediatric subgroup of patients who were previously using ivacaftor was the only population to show a decrease in BMI percentile; however, this group included only two patients.
There were a few limitations to this study. The COVID-19 pandemic reduced the number of in-person follow-up visits, as many quarterly clinic visits were converted to telehealth visits that excluded the possibility of collecting height and weight. Additionally, the retrospective aspect of this study led to the inability to assess some complications in a nuanced way. Our small cohort also made it challenging to explore other relevant outcomes, including the impact of TCT on weight in CFRD patients. It is essential to mention that compliance to all therapies could only be assessed by the documentation in medical records.
While this study helped build a more comprehensive understanding of weight gain in all types of CF patients, future more extensive studies will be needed to explore the mechanisms behind these changes. Additionally, with the recent FDA approval of TCT in 6–12-year-old children, the effect of TCT on BMI percentile will need to be evaluated in this population.
Overall, this study helped assess if TCT increases BMI in CF patients. More importantly, this study quantified the BMI gains on average that patients could expect to see after a year on the medication. This work allows for a greater understanding on an individual and systematic level. New information regarding the weight gain associated with HEMT allows patients to make more educated decisions about their nutrition while taking TCT and allows their providers to adjust recommendations and shift their focus to the possibility of excess weight gain in some patients. Ultimately, the consistent monitoring of nutritional needs is essential to build upon and correct CFF guidelines to fit the needs of all CF patients as their baseline health changes in the era of new modulators.