Relating Improvement in Gastrointestinal (CFAbd-Score©) and Sinonasal (SNOT) Symptoms During Therapy With Elexacaftor/Tezacaftor/Ivacaftor in CF Patients.

BACKGROUND

For people with cystic fibrosis (pwCF) carrying susceptible mutations, elexacaftor/tezacaftor/ivacaftor (ETI) has changed the course of their lives. Organ manifestations critically affecting both respiratory and digestive tracts have been found to improve considerably. Consequently, ETI-associated reductions in sinonasal symptoms (SNS) deriving from the upper respiratory tract are consistently reported. However, although substantial ETI-related declines in the burden of abdominal symptoms (AS) have been reported using the CFAbd-Score, their correlation with SNS changes has not been studied.

AIMS: Assessing correlations between ETI-related changes in pwCF SNS and AS.

METHODS

The German adapted version of the Sinonasal-Outcome-Test 20 (SNOT-20-GAV) and the CFAbd-Score, the first CF-specific gastrointestinal (GI) patient-reported outcome measure developed and validated following FDA guidelines, were simultaneously administered. PwCF completing both paired questionnaires, at least once before and after ETI initiation, were included.

RESULTS

In two German CF-centers, n = 31 pwCF (18 f, mean-age 13 years) were included, completing n = 106 paired questionnaires. During ETI therapy, significant decreases (p < 0.05) were observed for the mean total CFAbd-Score (10.9→5.8pts[-47%]) as well as all sub-scores ('pain': -61%, 'disorders of bowel movement': -56%, 'GERD': -54%, 'disorders of appetite': -50% and 'QoL-impairment':-67%). Analogously, SNS significantly improved (total SNOT: 10.1→3.4pts[-66%] and its 3 domains: primary and secondary nasal symptoms, and SNS-related QoL [-68%/-81%/-54%]). However, the correlation between changes in symptoms related to upper-respiratory and GI tracts was only modest.

CONCLUSION

The burden of symptoms captured with the CFAbd-Score and the SNOT-20-GAV significantly and markedly decreased after ETI initiation. The modest association between changes in both organ-specific symptom scores supports the previously reported individualized electrophysiological responses observed in nasal-potential and intestinal-current measurements.