Pancreatic status
One question that research has tried to answer regarding CFTR modulators
is whether or not they can improve or reverse pancreatic insufficiency,
since it is affects 85% of pwCF and the pathophysiology begins in
utero. Munce et al described 3 patients who had alterations in
pancreatic function with iva. Each of the patients had FE measurements
that were low (patient one: 40 mcg/g at 2 weeks of age, patient two: 50
mcg/g at 1 month and patient 3: 61 mcg/g at 3 months). All were started
on iva at varying ages: 4 years, 6 years and 7 years, respectively, and
FE levels were in the pancreatic sufficient range after treatment for 2
years in patients 1 and 2, and after 4 months in patient
334. Hutchinson et al performed a retrospective
clinical review of 18 children in Ireland, with the G551D mutation, who
had started on iva over the last 11 years at their center: FE increased
in all but 1 person, with 11 out of 18 having FE levels
>200ug/g and having discontinued pancreatic enzymes without
abdominal complaints with a median follow up of 12 months (range 8-22
months)35. Those who achieved pancreatic sufficient
levels were more likely to have had detectable FE at baseline (8/11
versus 0/7, p<0.01), less likely to have a second severe
mutation (F508del or minimal function: 2/11 versus 6/7, p=0.01), and
more likely to be younger upon starting iva (4 versus 8.6 years,
p<0.001) 35. Similarly, a letter to the
editor in Pediatric Pulmonology from Wright B et al described a
report of an F508del homozygous patient with an FE of 65 mcg/g at 3
weeks of age, who started lum/iva at age 6 and had repeat FE
measurements at age 9 in the sufficient range of 366 and 348
mcg/g36. Smith H et al in Pediatric Pulmonology
wrote a letter to the editor highlighting a case in an older child with
a FE <15 mcg/g at 2 years of age who started on iva at 14
years of age, who then became non-adherent to his pancreatic enzyme
replacement therapy with no signs or symptoms of malabsorption. Repeat
FE at age 17 was 263 mcg/g37. This case is relevant as
it suggests a patient may become pancreatic sufficient if a CFTR
modulator is started in the teenage years, as opposed to earlier in
childhood when pancreatic function is more likely to be impacted.
Measurement of pancreatic function throughout childhood on CFTR
modulators is an important parameter to assess, especially with the use
of the highly effective modulator ETI.