Longer term follow-up of abdominal symptoms (CFAbd-Score) after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis

Background: Whether improvements in gastrointestinal (GI) symptoms observed with Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment are sustained in the longer-term requires exploration. This study investigated how GI-symptoms change with longer-term ETI use in pancreatic insufficient adults with cystic fibrosis (awCF).

Methods: Participants completed up to three abdominal symptom questionnaires, employing the validated CFAbd-Score. Changes in total CFAbd-Score and its five domains, pain, gastroesophageal reflux-disease (GERD), disorders of bowel movement (DBM), disorders of appetite (DA) and quality of life (QOL), were analysed pre-ETI (T0) and at ≤1.5 years (T1) and 2-4 years of ETI-therapy (T2).

Results: A total of 165 CFAbd-Scores from 68 participants were analysed (median age: 34 years; IQR: 28-39). Total CFAbd-Score significantly (p < 0.05) and clinically meaningfully decreased from 20.4 ± 1.6 pre-ETI (median:40 weeks pre-treatment) to 15.3 ± 1.9 and 16.8 ± 1.6 at T1 (median: 25 weeks of ETI) and T2 (median: 148 weeks of ETI), respectively. The CFAbd-Score´s domains DA and QoL only significantly decreased between T0 and T1, whereas DBM only significantly decreased after 2-4 years of ETI therapy (T2). GERD scores were significantly lower at both T1 and T2.

Conclusion: While GI symptoms in awCF significantly improve within the first 1.5 years of ETI-therapy, they appear to somewhat wane with longer-term use, despite GI-symptom burden still being lower compared to pre-ETI. However, we cannot differentiate whether this results from reduced adherence, a decrease in ETI effects, or long-term changes in diet, gut microbiota or symptom perception. The longer-term impact of ETI and other potential modulator therapies on GI symptoms requires ongoing monitoring.