Background: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score.Methods: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations.Results: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2→10.6 ± 1.4; p < 0.01). Also EMMs of all five domains significantly declined (“pain” 16.3 ± 1.6→10.2 ± 2.3, “GERD” 15.8 ± 1.8→8.2 ± 1.9, “disorders of bowel movement” 20.9 ± 1.5→16.0 ± 1.7, “disorders of appetite” 7.9 ± 1.1→2.6 ± 1.1 and “quality of life impairment” 10.1 ± 1.92→3.9 ± 1.9). However, during 24 weeks, CF participants’ symptoms mostly still did not reach the reference levels of HCs.Discussion: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI.
Background: Rate of change in lung function is used as a measure of disease progression and a predictor of mortality in individuals with cystic fibrosis (CF). The aim of this study was to determine the national rate of decline in percent predicted Forced Expiratory Volume in 1 second (ppFEV 1 ) in adults in the UK accounting for age, sex and pancreatic status.Methods: Data on ppFEV 1 for adults with CF, excluding those post lung transplantation, was extracted from the UK CF registry between 2015 and 2017. Multilevel modelling was conducted to calculate the annual rate of change in ppFEV 1 accounting for age, sex and pancreatic status.Results: Overall annual ppFEV 1 decline was -1.52% (95%
Background The underlying mechanisms of chemotherapy-induced gastrointestinal (GI) symptoms are poorly researched. This study characterised the nature, frequency, severity and treatable causes for GI symptoms prospectively in patients undergoing chemotherapy for GI malignancy. Methods Patients receiving chemotherapy for a GI malignancy were assessed pre-chemotherapy, then monthly for 1 year using the Gastrointestinal Symptom Rating Scale, a validated patient-reported outcome measure. Patients with new, troublesome GI symptoms were offered investigations to diagnose the cause(s). Their oncologist was alerted when investigations were abnormal. Results A total of 241 patients, 60% male, median age 63 years (range 30-88), were enrolled; 122 patients were withdrawn, 93%, because of progressive disease or death. During the study, > 20% patients reported chronic faecal incontinence and > 10% reported moderate or severe problems with taste, dysphagia, belching, heartburn, early satiety, appetite, nausea, abdominal cramps, peri-rectal pain, rectal flatulence, borborygmi, urgency of defecation or tenesmus. Thirty percent reported continuing passage of hard stools and 30% ongoing diarrhoea. Moderate or severe fatigue affected 40% participants at its peak and persisted in 15% at 1 year. Toxicity dictated change in chemotherapy for 13-29% patients/month. Common Terminology Criteria for Adverse Events underestimated gastrointestinal morbidity. Pre-chemotherapy screening identified previously undiagnosed pathology: exocrine pancreatic insufficiency (9%), vitamin B 12 deficiency (12%) and thyroid dysfunction (20%). Patients often refused investigations to diagnose their chemotherapy-induced symptoms; however, for every three investigations performed, one treatable cause was diagnosed: particularly small intestinal bacterial overgrowth (54%), bile acid malabsorption (43%), previously not described after chemotherapy, and unsuspected urinary tract infection (17%). Conclusions Patients undergoing chemotherapy for GI malignancy commonly have difficult GI symptoms requiring active management which does not occur routinely. The underlying causes for these symptoms are often treatable or curable. Randomised trials are urgently needed to show whether timely investigation and treatment of symptoms improve quality of life and survival. Trial registration ClinicalTrials.gov Identifier: NCT02121626
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