Effect of newer CFTR modulator therapy on glycaemic control in adolescents with CFRD

Julie Park; Anna Walsh; Sue Kerr; Clare Woodland; Suzanne Southward; Mark Deakin; Rebecca Thursfield; Senthil Senniappan

Background: Cystic fibrosis related diabetes (CFRD) affects 40-50% of adults with Cystic Fibrosis (CF) and significantly decreases pulmonary function and affects life expectancy. Previous data highlighted that CFRD may be preventable or curable with the use of CFTR modulators, namely Ivakaftor. Kaftrio (Ivakaftor, tezacaftor and elexacaftor) has recently been licensed for use in CF. To our knowledge, its effect on glucose regulation in children and young people (CYP) with CFRD has not been described.

Objective: To describe the effect of Kaftrio on blood glucose control in CYP with CFRD who have previously been treated with insulin.

Methods: 7 patients (M: F = 1: 6) with at least one ∆F508 gene and one other licensed gene change were commenced on Kaftrio. A Freestyle Libre glucose monitoring system (Libre) was inserted three to five days prior to the initiation of the drug and monitoring was continued for the first 10 days after Kaftrio and then at regular intervals. Insulin dose was reduced prior to commencement of the drug or stopped if the dose was small. Regular blood glucose monitoring via finger prick and libre scanning, along with clinical symptoms were used to determine ongoing insulin requirement.

Results: 5/7 (71%) patients no longer require insulin, 1/7 (14.2%) required significantly less insulin, 1/7 (14.2%) showed increasing insulin requirements (as detailed in table below).

Discussion: The data from our study suggest that Kaftrio leads to significant improvement in blood glucose control in CYP with CFRD which is sustained over five to thirteen months. Further data on long term effect needs to be assessed. Insulin doses should be reduced and CYP should be monitored closely when commencing treatment with Kaftrio.

Table 1 Demographics of population
Parameter	Mean ± SD
Age at diagnosis of CFRD (years)	11.5 ± 1.9
Age when Kaftrio commenced (years)	14.0 ± 1.1
Length of time on Kaftrio (months)	7.0 ± 2.7

Table 2 Insulin requirements before and after Kaftrio therapy
Patient	Dose of insulin prior to commencing Kaftrio (units/day)	Dose of insulin post Kaftrio (units/day) (at a variable duration of 5-13 months)
1	6	0
2	8	0
3	25	1
4	2	0
5	10	0
6	28 units Tresiba + ICR* 1:12 + ISF** 1:4	30 units Tresiba + ICR* 1:15 + ISF** 1:4
7	4	0
ICR = insulin to carbohydrate ratio *ISF = insulin sensitivity factor

ESPE Abstracts

FC4.4