Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis

Abstract

BackgroundA method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available.ObjectivesTo assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD.MethodsA prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA.ResultsMedian CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account.ConclusionStrict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidence-based method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings.

Enzyme replacement treatment in exocrine pancreatic insufficiency associated with cystic fibrosis. Cystic fibrosis Working group of the Latin American Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPHGAN)

“…De las más de 2 mil variantes del gen FQ, la más común es la deleción del alelo F508 del gen CFTR (∆F508 o F508del), que se halla en aproximadamente 70% de los alelos CFTR defectuosos, variando según el grupo étnico. La mayoría de los homocigotos F508del tienen IPE, mientras los heterocigotos tienen función pancreática residual, pudiendo evolucionar hacia la IPE (2)(3)(4).…”

“…Tratar la malabsorción para optimizar el crecimiento y el estado nutricional es clave (9). La terapia de reposición con enzimas pancreáticas (TREP), ha mostrado eficacia para compensar la malabsorción, logrando crecimiento y estado nutricional óptimos, con síntomas mínimos (2,3,9,10).…”

Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis

“…We showed that the optimal dose for maximal lipid digestion is mainly dependent on food characteristics and developed a mathematical predictive algorithm (MPA) that establishes the optimal PERT dose based on food properties [10] . This was tested in a pilot study, resulting in a median coefficient of fat absorption above 90% [11] . The PERT calculation method was implemented into the app to assist patients to optimize their PERT dose.…”

Assessing gastro-intestinal related quality of life in cystic fibrosis: Validation of PedsQL GI in children and their parents

“…The MyCyFAPP project aims to develop and validate a mobile application (APP) to optimize and personalize the intake of PERT [10]. An algorithm, integrated in the APP, was developed to determine the optimal PERT dose needed per meal, based on in vitro data of food digestion [11–12]. In the final phase of the project, a European multicentre prospective clinical trial was planned to assess the impact of the use of the APP on patient outcomes.…”

“…The first is the CF-specific QOL questionnaire, the CFQ-R [15–17], to be used for children and their parents from 6 years onwards. Thus far, only the respiratory domain of this scale has been approved as endpoint by the FDA [12] and was used as a primary outcome parameter in only a few clinical trials [18–19]. The child version of CFQ-R includes a domain assessing abdominal quality of life (digestion), but this scale includes only 7 items and does not cover all relevant GI aspects in CF; it was therefore considered not suitable as a primary outcome parameter in the MyCyFAPP project.…”