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Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI

Published:October 21, 2022DOI:https://doi.org/10.1016/j.jcf.2022.10.003

      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)
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