Small improvements in gastrointestinal (GI) symptoms have been reported in patients with cystic fibrosis (CF) who receive elexacaftor/tezacaftor/ivacaftor (ETI) therapy, according to the results of a prospective, observational study published in the Journal of Cystic Fibrosis.
The 56-center PROMISE study (NCT04038047) was conducted in people with cystic fibrosis aged at least 12 years who reported 1 or more F508del allele. Although treatment with ETI has been shown to improve pulmonary disease in people with CF, the impact of this therapy on GI symptoms—which are known to affect quality of life—is not clear.
PROMISE-GI measured GI symptom frequency and severity among people with CF via patient-reported outcome measures (PROMs) from 3 validated GI questionnaires—the Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM) severity index, Patient Assessment of Constipation-Symptom (PAC-SYM) severity index, and Patient Assessment of Constipation-Quality of Life (PAC-QOL)—and 1 stool-specific questionnaire.
Associations between changes in fecal calprotectin and changes in several core outcomes at 1 month and at 6 months were evaluated as well. The relationship between change in fecal calprotectin and change in PROM scores at 6 months also was examined. Steatocrit and elastase were measured in stool as well.
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A total of 438 individuals completed at least 1 PROM. Mean PAGI-SYM, PAC-SYM, and PAC-QOL scores at baseline were 0.56, 0.47, and 0.69, with possible maximum scores of 5, 4, and 5, respectively. Higher scores were indicative of greater severity.
Respective age- and sex-adjusted 6-month mean changes in total scores were –0.15 (95% CI, –0.21 to –0.09); –0.14 (95% CI, –0.10 to –0.09); and –0.15 (95% CI, –0.21 to –0.10). Although these changes were statistically significant, they were small and not likely to be of clinical importance.
Additionally, fecal calprotectin revealed a significant change from baseline of –66.2 μg (95% CI, –86.1 to –46.2), but fecal elastase and steatocrit did not demonstrate any statistically significant changes.
“After 6 months of ETI, fecal markers of inflammation decreased. [GI] symptoms improved, but the effect size was small. Pancreatic insufficiency did not improve,” the authors concluded. “Ongoing and planned studies of ETI in younger children may demonstrate a greater impact on [GI] symptoms and pancreatic function.”
Overall, 49.3% of the participants were male and 93.8% were White. The mean patient age was 25.0±10.6 years.
Schwarzenberg SJ, Vu PT, Skalland M; PROMISE Study Group. Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: report of Promise-GI. J Cyst Fibros. Published online October 21, 2022. doi:10.1016/j.jcf.2022.10.003