Highlights
- •After 6 months of ETI there is modest improvement in gastrointestinal symptoms in people with CF.
- •ETI reduces markers of intestinal inflammation after 6 months.
- •In CF >12 years of age, there was no improvement in fecal elastase after 6 months of ETI.
Abstract
Background
Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic
fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality
of life, is not clear.
Methods
PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and
at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient
Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment
of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life
(PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and
6 months after ETI initiation. Mean difference and 95% confidence intervals were obtained
from linear regression with adjustment for age and sex.
Results
438 participants fully completed at least 1 questionnaire. Mean (SD) for baseline
PAGI-SYM, PAC-SYM, and PAC-QOL total scores were 0.56 (0.59), 0.47 (0.45), and 0.69
(0.53) out of maximum 5, 4, and 5, respectively (higher score indicates greater severity).
Corresponding age- and sex-adjusted 6 months mean changes (95% CI) in total scores
were -0.15 (-0.21, -0.09) for PAGI-SYM, -0.14 (-0.19, -0.09) for PAC-SYM, and -0.15
(-0.21, -0.10) for PAC-QOL. While statistically significant, changes were small and
unlikely to be of clinical importance. Fecal calprotectin showed a change (95% CI)
from baseline of -66.2 µg/g (-86.1, -46.2) at 6 months, while fecal elastase and steatocrit
did not meaningfully change.
Conclusions
After 6 months of ETI, fecal markers of inflammation decreased. Gastrointestinal symptoms
improved, but the effect size was small. Pancreatic insufficiency did not improve.
Keywords
Abbreviations:
BMI (body mass index), CF (cystic fibrosis), CFTR (cystic fibrosis transmembrane conductance regulator), ETI (elexacaftor/tezacaftor/ivacaftor), FEV1pp (forced expiratory volume in 1 second percent predicted), GI (gastrointestinal), MCID (minimal clinically important difference), PAGI-SYM (patient assessment of upper gastrointestinal disorders-symptom severity index), PAC-SYM (patient assessment of constipation-symptom severity index), PAC-QOL (patient assessment of constipation-quality of life), PROM (patient reported outcome measure), PwCF (people with cystic fibrosis), S (supplemental), SSQ (stool-specific questionnaire)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: October 21, 2022
Accepted:
October 10,
2022
Received in revised form:
September 12,
2022
Received:
April 10,
2022
Publication stage
In Press Corrected ProofFootnotes
☆Results were previously presented at the North American Cystic Fibrosis Conference in 2020 and 2021.
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
