Neuropsychological side effects remain 6 months into cystic fibrosis triple therapy

Key takeaways:

• Neuropsychological side effects included insomnia, headache, brain fog and memory and concentration problems.
• Despite persistent side effects, patients had improved cognitive processing, depression and more.

At three follow-up visits within 6 months, reports of neuropsychological side effects rose or stayed stable among patients with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor therapy, according to results published in CHEST.

Additionally, over 6 months of elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta, Vertex Pharmaceuticals) treatment, patients had improved depression, cognitive processing and health-related quality of life in seven of 12 domains, according to researchers.

“The current study suggests that [people with cystic fibrosis] starting ETI should be followed up systematically to assess the effects of ETI on the whole person,” Sonia Graziano, PsyD, research coordinator of the Italy Harvard Program in Refugee Trauma and in the unit of clinical psychology at Bambino Gesù Children’s Hospital, and colleagues wrote.

In a prospective, real-world longitudinal study, Graziano and colleagues assessed 92 Italian adults and adolescents (mean age, 25.4 years; 50% male; 78.2% adults; 22.8% adolescents) with cystic fibrosis receiving ETI triple therapy for the first time to determine the impact the treatment has on depression, anxiety, cognitive processing and health-related quality of life at 1, 3 and 6 months.

Researchers also collected reports of GI symptoms via the GI Symptom Tracker and neuropsychological side effects (insomnia, headache, memory problems, brain fog and concentration problems) through an ad hoc questionnaire.

Compared with the baseline mean FEV₁ percent predicted of 74.71%, there was a significant rise in mean FEV₁ percent predicted at 1 month (83.56%), 3 months (84.19%) and 6 months (83.25%). Significant improvement was also noted in BMI as the average went up from 21.64 kg/m² to 23.32 kg/m² at 6 months.

After 1 month of receiving ETI, researchers observed a significant improvement in depression via nine-item Patient Health Questionnaire scores, which went down from a mean 3.69 points to 2.87 points. This outcome was also observed when analyzing average scores at 3 months (2.73 points) and 6 months (2.74 points).

In contrast, mean seven-item Generalized Anxiety Disorder scores at all three follow-ups did not significantly differ from the baseline score.

Patients’ cognitive processing was measured using the Symbol Digit Modalities Test, and at each follow-up visit, mean test scores improved compared with baseline (46.37 vs. 1 month, 49.67; 3 months, 52.98; 6 months, 54.52).

In terms of health-related quality of life, seven of the 12 domains on the Cystic Fibrosis Questionnaire-Revised significantly improved over time: physical functioning (baseline < each follow-up), vitality (baseline < each follow-up), health perception (baseline < each follow-up), social/school functioning (baseline < 6 months), role (baseline < 6 months), weight (baseline < 3 and 6 months) and respiratory symptoms (baseline < each follow-up). The five domains with no significant improvement included emotional functioning, eating problems, treatment burden, body image and digestion, according to researchers.

Data from the GI Symptom Tracker revealed fewer stools, adherence challenges and eating challenges as months passed from the start of ETI treatment. The baseline stool mean was 15.89, which gradually went down at 1 month (15.43), 3 months (13.57) and 6 months (12.39).

For adherence challenges, the baseline average was 12.82, and this declined at 1 month (9.7) and 3 months (8.65). Similarly, the baseline eating challenges mean was 13.86, and this gradually became lower at 1 month (13.17) and 3 months (10.51). Reports of abdominal pain persisted across the follow-up visits.

Within the total cohort, 10% to 29% said they experienced one of the five studied side effects at 1 month. The proportion of patients reporting one of the five side effects was also similar at 3 months (9.9% to 30.4%) and 6 months (10.9% to 27.2%).

Insomnia was the only side effect in which the proportion of patients reporting it was significantly greater with each visit (1 month, 12.1%; 3 months, 16.1%; 6 months; 17.4%), according to researchers.

After dividing the study population according to sex, researchers found a higher proportion of patients with insomnia, headache, brain fog and concentration problems in the female vs. male group.

“This study offers guidance on which side effects to measure over time, and because ETI is prescribed for school-aged children and downwardly extended to preschool-aged children, we recommend they also be monitored,” Graziano and colleagues wrote.