Cystic Fibrosis, Digestive System Disease, Distal Intestinal Obstruction Syndrome, Gastrointestinal System Disease, Lung Diseases, Pancreatic Disease, Pancreatic Enzyme Abnormality
Conditions
Keywords
Cystic fibrosis, Distal Intestinal Obstruction Syndrome, Pancreatic enzyme replacement therapy, Gastrointestinal symptoms, Gut symptoms
Brief summary
To elucidate the similarities and distinctions in non-pulmonary manifestations of cystic fibrosis (CF) including distal intestinal obstruction syndrome (DIOS) incidence and pancreatic enzyme replacement therapy (PERT) use between US and UK CF populations in a parallel study using data from the UK and US CF registries. To assess how CFTR modulators impacted upon recorded PERT use and incidence of DIOS.
Detailed description
Cystic fibrosis (CF) is a autosomal recessive multi-system disorder caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As well as the documented respiratory complications of CF, gastrointestinal manifestations are of clinical importance. CFTR mutations in the gastrointestinal tract are responsible for pancreatic exocrine insufficiency in around 85% of people with CF (pwCF). In addition a severe gastrointestinal complication in CF is distal intestinal obstructive syndrome (DIOS), affecting 5.7% pwCF in the UK (2.5% in \<16 years and 7.7% in adults) and 2.1% in the US (\<18 years 1.7%, adult 2.4%) in 2019. This is a parallel data registry study using data from the UK and US CF registries, with data provided for the time period 2007-2018. As such no individual participants will be recruited to the study. The CFTR modulators to be studies are Ivacaftor and lumacaftor/ivacaftor. Study aims; * Describe DIOS events and PERT usage in UK and US registries * Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population time series * Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series The outcomes of the above aims will be used to generate hypotheses regarding the effect of the newer CFTR modulators such as Symdeko/Symkevi and Tricaftor/Kaftrio on PERT usage and DIOS incidence in CF registry data post 2018. This will form the basis of future studies.
Interventions
OTHERNo intervention
Registry study: No intervention
Sponsors
The Leeds Teaching Hospitals NHS Trust
Royal Brompton & Harefield NHS Foundation Trust
University of Washington
Seattle Children's Hospital
Nottingham University Hospitals NHS Trust
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* All patients with CF of any genotype on the UK and US cystic fibrosis registries from the period 2007 - 2018.
Exclusion criteria
\- Patients whose CFTR modulator status is unknown or only have one year of CFTR data recorded on the registry will be excluded from the analysis of the effects of CFTR modulators. This is to account for the fact that DIOS data is annualised on the registries, therefore there is no certainty at what time of year DIOS was diagnosed in relation to commencing CFTR modulator therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Describe DIOS events and PERT usage in UK and US registries 2007-2018 | 2 years | Descriptive analysis to include cumulative incidence of DIOS and prevalence of PERT usage in the UK and US. PERT use will be dichotomised (i.e use/no use), incidence of DIOS (event/no event), plotted by year, separated by registry. Trends will be described according to age range (\<6, 6-11, 12+), sex, BMI, ethnicity, antibiotic use, gastrointestinal co-morbidities and FEV1 lung function. These demographics will also be used for demographic propensity matching to define a control group of non-eligible non-users of CFTR modulators that are otherwise representative of the CFTR modulator user group the year that the CFTR modulator exposure was commenced. |
| Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: population level controlled interrupted time series (ITS) | 2 years | This will investigate the effect of CFTR modulator intervention on the rate on PERT use and DIOS incidence. ITS will explore proportion of DIOS events at population level in the CFTR modulator population and the propensity score defined comparator population. ITS will explore proportion of overall PERT usage (user/non user), and the proportion of individuals with a reduction in weight standardised PERT dose (decrease/no decrease). |
| Determine the effect of CFTR modulators on the incidence of DIOS and use of PERT: patient-level time series | 2 years | This will focus on patient level associations to complement the registry level findings. Associations in the incidence of PERT usage and DIOS events from 2012 in individuals taking CFTR modulators, compared to propensity matched controls will be explored. DIOS events: Multilevel Poisson Regression model for count data by year, incidence rate ratio (frequency of DIOS events). Adjusted analysis for main covariates. PERT use: Multilevel linear regression for continuous data, multilevel logistic regression for dichotomised data. Adjusted for main covariates. |
Countries
United Kingdom
Outcome results
None listed