New Method to Determine Best PERT Dose Shows Potential in Young CF Patients, Pilot Study Reports

A new method to estimate the best dose of enzyme supplements for pancreatic enzyme replacement therapy (PERT) based on different meals shows promise in young patients with cystic fibrosis (CF), according to a pilot study.

According to the test, doses do not need to be adjusted based on patients’ individual differences, such as age, gender, or body mass index. The type of food eaten seems to be the most important factor in determining the amount of enzymes that should be taken for the best possible nutrition.

The method could potentially be implemented in clinical practice to help physicians and CF patients decide on the best PERT doses, possibly contributing to more efficient digestion and absorption of nutrients, the researchers say.

The study “Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis” was published in the journal PLOS ONE.

Up to 90 percent of CF patients need to take enzymes before they eat. This is because a thick mucus in the pancreas blocks the discharge of enzymes needed for digesting carbohydrates (sugars), fats, and proteins in food. To prevent malnutrition, CF patients with pancreatic insufficiency are treated with PERT, which generally consists of oral capsules containing pancreatic enzymes.

Patients usually take PERT as a fixed dose per day or adjust it to the type of food they will eat, for instance, increasing the dose prior to a fatty meal. This implies that patients “have to decide the dose of enzymatic supplement to take every single time they eat,” the researchers wrote.

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Due to this, there are “large differences in dosing criteria … evidencing the lack of a common consensus,” the team said. Inaccuracies in choosing doses has been suggested as a reason why fat absorption remains insufficient in most CF patients.

To overcome this problem, researchers from several European institutions have joined together to develop MyCyFAPP Project, funded by the European Union. Its goal is to establish an efficient method to help CF patients and doctors identify the most appropriate dose of enzyme supplements.

To do this, the team created a test to determine a theoretical optimal dose (TOD) of enzyme supplements per food product, but so far, the tool has only been tested in the laboratory. Now researchers have gone a step further and sought to validate the method in CF patients.

In the study, they evaluated the variability in fat absorption between CF patients after they had eaten a predefined diet and taken the optimal dose of enzymes determined by the new method.

A total of 43 young patients, ages 2 to 18 years, referred to five European CF centers, were evaluated. They were asked to follow a fixed diet for 24 hours, and to take the TOD of enzyme supplements for each meal. The enzymatic supplements were enteric-coated microspheres of porcine-origin pancreatin, including amylase (to digest sugars), protease (to digest proteins), and mainly lipase (to digest fats).

The diet prescribed for the test was composed of six meals over 24 hours and a washout diet period consisting of three meals before and after the test diet. Nutrient distribution was approximately 40% lipids (fats), 40% carbohydrates, and 20% protein.

To evaluate the efficiency of nutrient digestion and absorption, the coefficient of fat absorption (CFA) was determined for each patient. CFA, which is the percentage of absorbed fat in the diet, is calculated by determining the amount of fat lost in the feces, given the total amount of fat consumed.

Results showed that taking the TOD of enzymes calculated by the new tool led to a median CFA of 90%, with little variability between patients. This value is slightly better than the one reported in previous studies, and comparable with others without a predefined dose, according to the researchers.

Data also confirmed that optimal doses of enzymes varied significantly due to not only the amount of fat, but also the food characteristics, such as the quantities of other nutrients and the type of food matrix.

Moreover, the results indicate that the digestion of fat is more dependent on the type of food than on individual patient characteristics. No statistical associations were found between CFA and patients’ age, gender, type of CFTR mutations, or body mass index.

According to the team, the findings may offer a new perspective on the treatment of pancreatic insufficiency in CF. They also suggested that the newly developed method to adjust PERT “could be implemented in the clinical practice to support clinicians and patients’ decision on the dose of the enzymatic supplement.”

“Ideally, a dose tailored at each single meal could be foreseen,” they said.

To allow patients to self-manage PERT, the researchers have developed a mobile app that calculates the optimal dose of enzymatic supplements based on a database of TODs. Next, they want to assess the effects of using this app on health and quality of life outcomes of those with CF.