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.