CFTR modulator triple combination therapy not only drives physical improvement in patients with cystic fibrosis, but also recalibrates their sense of identify across physical, social and psychological domains of life, Australian research shows.

The mixed methods study involved 20 adults from Sir Charles Gairdner Hospital Adult Cystic Fibrosis Clinic in Perth, who had been receiving elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) for 10-24 months.

The research included a mix of data collected from patient medical records, short-form surveys and interview responses.

Findings showed that following the initiation of ETI therapy, mean lung function rose significantly (71.30 to 77.70 FEV1%) and the mean frequency of pulmonary exacerbations in the preceding 24 months reduced significantly (4.25 to 0.90).

While self-concept scores did not significantly differ before and after ETI initiation (mean 48.25 vs 49.70, indicative of average self-concept), thematic analysis of interview data highlighted that many participants had experienced a recalibration across physical, social, and psychological domains related to ETI.

First author Dr Maggie Harrigan, Institute for Respiratory Health and UWA, Perth.

Physically, participants reported experiencing a “new CF”, which involved a shift in their self image towards that of a physically healthier person.

This shift was driven by reduced symptoms like coughing, reduced treatment and hospitalisations, and an increase in energy and physical capability, along with renewed life goals.

“You have close friends that will say to you they notice you are not coughing so much, you don’t breathe in the middle of sentences … It kind of just feels like you’re a lot more normal,” one participant said, summing up a common sentiment among the interviewees.

While there was no significant difference in BMI in the quantitative data, weight gain emerged as a challenging aspect of taking ETI in the qualitative findings.

Some participants noted the mental shift of gaining a lot of weight for the first time after a lifetime of being a low body weight and requiring a high calorie diet. This had impacts on their diet and their body image, with one participant calling the adjustment “weird, unusual and challenging”.

Another said his self-image was “probably the worst it’s ever been in my entire life” and that he was also “heaviest I’ve ever been”.

There was also a psychological recalibration when it came to time, as patients were used to their days being dictated by symptoms and treatment as well as being very calculated with their limited time due to reduced life expectancy.

Following ETI, they had newfound flexibility and freedom.

This led to a broadening of goals and possibilities across family, relationships, career and travel that were previously viewed as too difficult. No longer having ‘the mortality shadow’ also promoted future thinking and long-term goal setting, the researchers noted.

“I went from going … ‘I’m probably not going to see retirement age’ to ‘I am going to last as long as is possible for somebody male in my family’, and that’s outright incredible,” one participant said.

But another reflected: “I didn’t go to uni because I didn’t want to waste my life on uni. Now that I have all these extra years, what am I going do with that? It’s a whole new life and you’ve got to get used to that.”

Importantly, not all experiences were positive, with those who had significant disease burden and ETI-related side effects describing a sense of feeling “different” from others in the CF community who viewed ETI as a “wonder drug”.

The authors recommended integrating self-concept support into routine CF care, to navigate shifting life expectancy, body image, dietary adjustments and improved health perceptions which might reduce adherence to burdensome treatments.

“The General Mental Health Screener for CF (GEMS-CF), currently undergoing validation, may help identify these issues and facilitate broader conversations about mental health and self-concept,” they added.

The study was published in The Patient: Patient-Centered Outcomes Research [link here].

Some authors reported receiving payment from Vertex Pharmaceuticals outside of the study or being involved in Vertex Pharmaceuticals clinical trials.