P28 An audit of liver function testing in paediatric patients newly started on Kaftrio®
Authors: Bayliss Emily 
Published: April 2023

Aim

To investigate whether the current practice of liver function test (LFT) monitoring within a large tertiary paediatric cystic fibrosis centre adheres to local and national guidelines with respect to baseline monitoring, frequency of monitoring in the first year of treatment and action taken in the event of abnormal results for patients newly started on Kaftrio® treatment.

Method

All patients currently receiving Kaftrio® treatment were identified. Patients were excluded if they had not been on treatment for one year, if they had prolonged gaps in treatment or if they had bloods taken at outreach clinics with results not accessible to the investigator. Data was retrieved from each patient’s electronic laboratory reports and recorded on a data collection form. Data collected included: date Kaftrio® started; did the patient have baseline LFTs within one year before starting; did the patient have their first LFTs done 3 months after starting; in the first year did the patient have four sets of LFTs at 3-month intervals; were LFTs in range; if LFTs were abnormal was appropriate action taken. A 2-week tolerance was permitted. The data was analysed to assess compliance to guidelines. Assessments of transaminases (ALT and AST) and total bilirubin are recommended prior to initiating treatment then every 3 months during the first year of treatment.1–3Elevated ALT/AST two to three times the upper limit of normal (ULN) with normal serum bilirubin should prompt repeat LFTs within 8 weeks.1ALT/AST greater than five times ULN, or greater than three times ULN with high bilirubin warrants treatment being interrupted.1–3

Results

31 patients were reviewed. 30 patients (97%) had baseline LFTs. 10 patients (32%) had LFTs at 3 months. Of the 21 patients who did not, 15 of those had their first set of LFTs taken too early at 1 or 2 months and 6 were taken late at 4,5 or 6 months. Zero patients had four sets of LFT results taken at the correct 3-monthly intervals in the first year. 4 patients (13%) had at least one set of abnormal LFTs. 50% of abnormal results were acted upon in accordance with guidelines.

Conclusion

The results showed that, other than baseline monitoring, current practice is not in accordance with guidelines both in relation to frequency of LFT monitoring and appropriate action being taken on the finding of abnormal results. Further study is required to investigate the reasons for poor outcomes and how compliance with the guidelines can be improved. Encouragingly, the rate of liver impairment as an adverse drug reaction was low. Trial data should be reviewed to assess the significance of waiting until month 3 to start LFT monitoring (i.e. when do deranged LFTs typically first manifest?) and therefore whether early testing is problematic (in patients with no history of liver impairment). Guideline development should be an area of focus to put measures in place to improve guideline compliance. However, with MDT agreement, consideration should be given to adapting local practice to deviate from national guidance to better fit real-world practice.

References

Trust guideline. Management of children with Cystic Fibrosis. (local access only).

Vertex Pharmaceuticals (Europe) Ltd (2022) Kaftrio 75 mg 50 mg 100 mg film coated tablets. Available at: https://www.medicines.org.uk/emc/product/11724/smpc [Accessed June 2022]

MHRA (2022) Drug Safety Update Ivacaftor, tezacaftor, elexacaftor (Kaftrio▾) in combination with ivacaftor (Kalydeco): risk of serious liver injury; updated advice on liver function testing. Available at: https://www.gov.uk/drug-safety-update/ivacaftor-tezacaftor-elexacaftor-kaftriov-in-combination-with-ivacaftor-kalydeco-risk-of-serious-liver-injury-updated-advice-on-liver-function-testing [Accessed June 2022]