Sub-tropical climate a focus for improving CF care

Could Brisbane’s sub-tropical climate affect how Metro North cares for people with cystic fibrosis?

The Prince Charles Hospital (TPCH) Consultant Thoracic Physician (Cystic Fibrosis, Bronchiectasis and Nontuberculous Mycobacteria) Dr Ieuan Evans said the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies since 2012 had transformed therapeutic treatment options for people with cystic fibrosis (CF).

“CFTR modulator therapy, particularly using Elexacaftor, Tezacaftor and Ivacaftor (ETI), can improve lung function, increase weight and improve bowel function for people with CF, enhancing their overall health and life expectancy,” Dr Evans said.

“ETI has been transformative for the management of cystic fibrosis.”

While lung function decline has been the major cause of morbidity for people with CF, CFTR modulator therapy using ETI can improve lung function, as well as increase weight and improve bowel function, enhancing overall health and life expectancy.

However, Dr Evans said up to 10 per cent of people on ETI could experience side effects including headaches, abdominal pain, diarrhoea, rash and, more concerningly, hepatic dysfunction.

The reason that hepatic dysfunction—known as hepatotoxicity—affects some people with CF and not others remains unclear. Some people with CF on ETI showed marked increases in liver enzymes, with case reports of hepatic necrosis also being reported. This often requires cessation or dose reductions of ETI, potentially impacting treatment outcomes.

Dr Evans is seeking to develop a therapeutic drug monitoring protocol for ETI that can be used in clinical practice. His aim is to better understand the association between drug levels, toxicity and side effects in people with CF to guide a personalised therapeutic strategy.

Thirty people with CF on ETI treatment will provide baseline demographic and clinical data alongside hourly blood samples over a nine-hour period after taking ETI.

Data collected from these people with CF will be used to create a pharmacokinetic profile that can be utilised to help evaluate whether adequate dosing is being achieved with ETI, especially in those on a dose reduction, for example, in the setting of hepatoxicity.

Anecdotally, some related adverse events can be limited by dose reductions.

Establishing the mechanisms by which hepatoxicity occurs in the context of ETI is a focus of ongoing research by members of the CF team.

Dr Evans said one hypothesis was that higher average temperatures and humidity could increase the risk of hepatoxicity in people with CF receiving ETI.

“Given Brisbane’s sub-tropical climate, inadequate hydration may be a factor in the development of liver dysfunction associated with ETI,” Dr Evans said.

“Our findings highlight the need for an increased understanding in the factors that govern the development of liver dysfunction secondary to ETI.

“Improved understanding of contributory factors, such as hydration status, will be essential for optimisation of ETI dosing protocols and improved long-term outcomes.”