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

J Cyst Fibros. 2023 Mar;22(2):282-289. doi: 10.1016/j.jcf.2022.10.003. Epub 2022 Oct 21.


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.

Trial registration: ClinicalTrials.gov NCT04038047.

Keywords: Inflammation; Modulators; Pancreatic insufficiency; Patient-reported outcomes measures.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminophenols
  • Benzodioxoles / therapeutic use
  • Constipation
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Humans
  • Mutation
  • Pancreatic Elastase
  • Prospective Studies
  • Quality of Life


  • elexacaftor
  • ivacaftor
  • tezacaftor
  • Aminophenols
  • Benzodioxoles
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Pancreatic Elastase

Associated data

  • ClinicalTrials.gov/NCT04038047