Appearance of Pancreatic Sufficiency and Discontinuation of Pancreatic Enzyme Replacement Therapy in Children with Cystic Fibrosis on Ivacaftor

Review of CFTR modulators 2020

“…In the study of lum/iva performed in the Netherlands in PwCF over age 6 years with FEV1pp ≥ 90%, 5 likely to be younger upon starting iva (4 vs. 8.6 years, p < .001). 23 Several case reports published in 2020 also note improvements in pancreatic exocrine function in older children following use of CFTR modulators [24][25][26] (Table 2). Adult studies have not yet shown improvements in pancreatic function on CFTR modulators, so it unlikely that adults can achieve pancreatic sufficiency if started on modulators later in life.…”

“…Hutchinson et al 23 performed a retrospective clinical review of 18 children (mean age = 5.8 years, range 1–11.4 years) in Ireland with the G551D mutation, who had started on iva over the last 11 years at their center: fecal elastase (FE) increased in all but 1 person, with 11 of 18 having FE levels > 200 μg/g and having discontinued pancreatic enzymes without abdominal complaints with a median follow up of 12 months (range 8–22 months). Those who achieved pancreatic sufficient levels were more likely to have had detectable FE at baseline (8 of 11 vs. 0 of 7, p < .01), less likely to have a second severe mutation (F508del or minimal function: 2 of 11 vs. 6 of 7, p = .01), and more likely to be younger upon starting iva (4 vs. 8.6 years, p < .001) 23 . Several case reports published in 2020 also note improvements in pancreatic exocrine function in older children following use of CFTR modulators 24–26 (Table 2).…”

Going the Extra Mile: Why Clinical Research in Cystic Fibrosis Must Include Children

“…As CFTR modulator access increases, real-world evidence is demonstrating that the early initiation of treatment is interrupting disease progression in multiple systems. In the main studies involving children aged 5 years and younger, several participants had an increase in faecal elastase, sufficient to recategorise them from pancreatic insufficient to pancreatic sufficient [ 29 , 30 ], and in other studies children were able to stop pancreatic replacement therapy [ 31 ]. The evidence for the impact of early initiation of treatment on glucose tolerance is mixed [ 32 , 33 , 34 , 35 ], and the impact on the risk of ultimately developing CF-related diabetes is unknown [ 36 ].…”

Review of CFTR Modulators 2020

“…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 3 34 . 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 .…”

“…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/g 36 .…”