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

Promise Study Group, Sarah Jane Schwarzenberg, Phuong T. Vu, Michelle Skalland, Lucas R. Hoffman, Christopher Pope, Daniel Gelfond, Michael R. Narkewicz, David P. Nichols, Sonya L. Heltshe, Scott H. Donaldson, Carla A. Frederick, Andrea Kelly, Jessica E. Pittman, Felix Ratjen, Margaret Rosenfeld, Scott D. Sagel, George M. Solomon, Michael S. Stalvey, John P. ClancySteven M. Rowe, Steven D. Freedman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)282-289
Number of pages8
JournalJournal of Cystic Fibrosis
Volume22
Issue number2
DOIs
StatePublished - Mar 2023

Keywords

  • Inflammation
  • Modulators
  • Pancreatic insufficiency
  • Patient-reported outcomes measures

Fingerprint

Dive into the research topics of 'Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI'. Together they form a unique fingerprint.

Cite this