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.