Patients with exocrine pancreatic insufficiency (EPI) have suboptimal secretion of pancreatic digestive enzymes and experience a range of clinical symptoms related to the malabsorption of fat. In patients with EPI unable to meet their nutritional requirements, enteral nutrition (EN) support is used to augment nutritional status. In addition to protein and carbohydrate, EN formulas contain fats as a calorie source, as well as vitamins and minerals to help prevent nutritional deficiencies related to malabsorption. Semielemental enteral nutrition formulas are advantageous as they contain hydrolyzed protein, shorter chain carbohydrates, and may contain medium chain triglycerides as a fat source. However, severely pancreatic insufficient patients may be unable to absorb complex long-chain triglycerides provided by EN formulas due to insufficient pancreatic lipase; replacement pancreatic enzyme products are recommended for these patients. Currently, none of the FDA-approved pancreatic enzyme replacement therapy (PERT) products are indicated for use in patients receiving enteral nutrition and administration of enzymes by mixing into enteral nutrition formula is not supported by guidelines as this route is associated with risks. RELiZORB (immobilized lipase) is a novel in-line digestive cartridge that has been designed to address the unmet need for PERT in patients receiving enteral nutrition. RELiZORB efficacy and compatibility with a range of commercially available polymeric and semielemental formulas with varying nutrient, caloric content, and triglyceride chain lengths have been demonstrated. In most formulas, RELiZORB efficiently hydrolyzed greater than 90% of fats within the formula into absorbable fatty acids and monoglycerides.
Am J Manag Care. 2017;23:-S0
Patients with exocrine pancreatic insufficiency (EPI) have suboptimal secretion of pancreatic digestive enzymes causing disruptions in the well-regulated digestive process, and patients with EPI experience a range of clinical symptoms related to the malabsorption of fat. Even with decreased enzymatic production from the pancreas, patients with EPI maintain physiological levels of protein and carbohydrate digestion due to the activity of extra-pancreatic amylase and proteolytic enzymes from gastric and salivary sources.1-3 However, pancreatic lipase is the principal enzyme responsible for lipolysis, digesting 40% to 70% of total triglycerides.4 Although lipolysis of triglycerides occurs in multiple sites throughout the digestive system, there is no redundancy in pancreatic lipase activity.2 More specifically, pancreatic lipase is required for the hydrolysis of the essential long-chain polyunsaturated fatty acids (LCPUFAs).5
Gastric lipase is responsible for 5% to 40% of dietary fatty acid breakdown products released in the stomachand hydrolyzes medium-chain fatty acid triglycerides (MCTs) with higher efficiency than long-chain fatty acid triglycerides (LCTs).4,5 Gastric lipase preferentially cleaves at the sn-3 position releasing a 1,3-diacylglycerol and a free fatty acid molecule.5 These lipolysis products stimulate a duodenal endocrine response, triggering the secretion of pancreatic enzymes including pancreatic lipase. Gastric lipase continues its enzymatic activity in conjunction with pancreatic lipase in the duodenum.4
The majority of lipid digestion and absorption occurs in the proximal small intestine, where pancreatic lipase cleaves triglycerides of any length at the sn-1 and sn-3 positions to generate 2 free fatty acids and a 2-monoglyceride molecule.4 Lingual lipase is secreted by lingual serous glands post-prandially and displays lipolytic activity in the stomach and duodenum. Lingual lipase acts on the sn-3 position to produce free fatty acid and diacylglycerol molecules, and is responsible for the breakdown of 10% to 30% of total dietary triglycerides with a 5- to 8-fold higher selectivity for MCTs compared with LCTs.6,7
As EPI progresses, dysfunctional pancreatic cells cannot produce adequate sodium bicarbonate to neutralize the highly acidic gastric secretions as they leave the stomach. The low pH leads to degradation of pancreatic and extra-pancreatic lipases and denaturation of bile salts.2,4 As a result, patients with EPI experience inadequate lipid digestion and nutritional deficiencies, and over time, may experience an increase in symptom severity due to insufficient redundancy of lipolytic activity throughout the digestive process.2 Consequences of abnormal lipid digestion include malnutrition, weight loss, abdominal discomfort, abdominal swelling, and fatty, loose, foul-smelling stools, or steatorrhea (defined as >7 g of fat in stool per 24 hours).2,4,8 Patients with EPI will most often require exogenous pancreatic enzyme supplements and may require enteral nutrition (EN) support to relieve malnutrition and clinical symptoms of fat malabsorption.3,9 In order to address the unmet needs associated with these treatments alone, a novel digestive enzyme cartridge (RELiZORB) has been developed to connect in-line with enteral feeding pumps for patients with EPI.
Approximately 44% of patients with cystic fibrosis (CF) require oral supplementation with EN; 11% require enteral tube feeding.9,10 Of the 10% to 15% of patients with chronic pancreatitis (CP) that require oral nutritional supplement, 5% of patients are indicated for enteral tube feeding.3 Given the insufficient pancreatic lipase activity in patients with EPI, lipid absorption varies depending on the content and structure of triglycerides available in a given EN formula (Table 15,6,11) Generally, 40% to 70% of the fat in semielemental and polymeric formulas contain primarily saturated MCTs (6-12 carbons), partially eliminating the need for pancreatic lipase or its cofactors for absorption.11-14 These EN formulas may help avoid nutritional deficiencies caused by the malabsorption of lipid-soluble vitamins (A, D, E, K) and macronutrients associated with EPI.8,12,15 However, essential LCPUFAs such as linoleic acid or linolenic acid still require pancreatic lipase for optimal hydrolysis.11 Linolenic acid serves as the precursor to the synthesis of omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); linoleic acid is the parent fatty acid to omega-6 fatty acids, such as arachidonic acid (AA). These essential fatty acids are involved in lipid homeostasis and critical for normal cell function, growth, as well as immune and vascular functions. As they cannot be synthesized de novo, adequate essential fatty acid levels depend entirely on dietary intake of the parent lipids or their derivatives for breakdown by pancreatic lipase, absorption, and transformation within the body.5,11,16
LCTs provide more calories per gram (higher energy density) than MCTs and provide LCPUFAs.3,11 Semielemental formulas may contain fixed amounts of LCTs to address caloric needs and provide essential fatty acids (Table5,6,11).11-13 However, severely pancreatic insufficient patients may be unable to absorb these complex chains appropriately without pancreatic lipase and as a result, patients with EPI may lack sufficient levels of essential fatty acids.3,11,12 Essential fatty acid deficiency has been reported in approximately 85% of patients with CF.5 As a solution, clinicians use exogenous pancreatic enzyme supplements to aid in the digestion and absorption of LCTs.11,17
Pancreatic Enzyme Replacement Therapy
More than 80% of patients with CP and CF are treated with pancreatic enzymes.3,9 Pancreatic enzyme replacement therapy (PERT) products are a mixture of porcine-derived pancreatic digestive enzymes indicated for oral administration in patients with EPI.18-23 The FDA-approved PERT products differ greatly in enzymatic activity due to different delivery of enzymes (ie, coating, microspheres, tablets, or capsules) and varying enzyme content (ie, lipase, protease, and amylase).8,24 As a result, inconsistent clinical efficacy has been demonstrated when comparing PERT products in patients with EPI.8,24
All but one of available PERT formulations are enteric-coated pancreatic enzyme microspheres or microtablets.18-21 This coating represents an attempt to increase resistance to degradation by gastric acid pH and proteases in the stomach to ensure delivery to the duodenum.17 Although the proteolytic pancreatic enzymes are more acid stable, lipase is irreversibly inactivated at a pH of 4 or less and subject to loss after administration if not protected.24 The PERT microspheres dissolve at a pH higher than 5.5, to protect enzymatic activity until they clear the stomach and enter the intestinal lumen.12,17,24 Enteric coated PERT may have variable efficacy for relief of steatorrhea based on the varying gastric and duodenal pH across patient populations with EPI.20,24 Both CP and CF are characterized by a progressive destruction of pancreatic cells. This results in enzymatic depletion and inadequate bicarbonate production and the inability to neutralize acidic chyme or solubilize lipolytic products for digestion. Patients with advanced CP and CF may also have increased gastric acid production. Therefore, CF and CP are characterized by a more acidic intraduodenal pH of 3 to 5 and PERT-derived lipase may never be released from the coating, limiting efficacy.1,4,25
The non-enteric coated PERT products must be used with a bicarbonate or acid-suppression medication (proton pump inhibitor) to raise gastric pH and prevent immediate degradation in the stomach.17,22,24 Administration of a 650-mg tablet of sodium bicarbonate (8 mEq) 2 or 3 times daily in conjunction with meals and PERT is recommended, with additional tablets administered at 1 hour and 2 hours after each meal although the effectiveness of this strategy is questionable.24 Another PERT formulation is buffered with bicarbonate for delayed release.23 In this way, the duodenal pH would theoretically increase without the need for concurrent acid-suppressive therapy.24 However, the low amounts of bicarbonate (2.5 mEq) in capsule PERT formulations may be insufficient to buffer the acidic gastric environment and prevent enzymatic degradation.23,26
Prior to 2010, the FDA did not regulate PERT products and the enzymatic activity of these products was unknown.17,24 In 2004, the FDA required manufacturers to meet efficacy and safety standards.24 Clinical trials of PERT efficacy enrolled fewer than 50 patients and measured short term efficacy compared with placebo treatment.17,18-20,22,24,27 The efficacy of PERT was demonstrated by improvements in fat absorption based on 72-hour stool collections. The primary end point of these randomized control trials was improvement in steatorrhea, as demonstrated by the mean difference in the coefficient of fecal fat absorption (CFA) with PERT compared with placebo treatment. Although CFA is more informative than the clinical presence or absence of steatorrhea, it does not directly measure fat maldigestion caused by EPI. PERT products demonstrated a 26% to 41% increase in CFA compared with placebo.18,20-23,28 However, some clinical trials included only patients who had achieved CFA improvements during a run-in phase with PERT therapy; as these trials excluded nonresponders to PERT, outcomes to PERT therapy may not be representative of the clinically treated population.19,24
Challenges with PERT treatment include limited guidelines for appropriate administration and lack of dosing standards between therapies (as none are bioequivalent).4,8,17 Enzymatic replacement therapy should be administered in the correct dosage in parallel with nutrients to coordinate gastric emptying, maximize efficacy, and ensure optimal absorption by mimicking the natural pancreatic secretion response to a meal.17,24 There is an unmet need for guidelines and standardization of therapy for patients with EPI (Table 21,12,17,29).
Selection of the PERT product and quantity of tablets needed for enzymatic activity is determined based on individual needs, such as dietary fat consumption, age, body weight, and disease state.17 Recommendations from various international societies (the Australian Pancreatic Club, the Italian Association for the Study of the Pancreas, and the Spanish Pancreatic Club) recommend 25,000 to 50,000 lipase units per meal.17 Many current dosing guidelines are for patients with CF or CP; in these patients, improvement of fat absorption has been reported using 40,000 units of lipase per meal and 20,000 units per snack. Other studies used anywhere from 40,000 to 80,000 lipase units with main meals 3 times a day, in addition to 20,000 to 50,000 with snacks 2 to 3 times a day on 100-gram fat diet.12
Cost is an additional consideration. The cost of PERT products can range from $0.92 per capsule (for a 4200 lipase unit capsule) to $8 per capsule (for a 36,000 lipase unit capsule).24 Furthermore, despite the expense and pill burden of PERT in patients with EPI, many patients still have symptoms.1 In a study from the Netherlands, 70% of patients with EPI caused by CP were undertreated and had steatorrhea-related symptoms, despite PERT treatment with 6 capsules of 25,000 units daily.17
EN and PERT
Further challenges arise with co-administration of available PERT in patients with CF or CP with EPI who cannot take nutrients by mouth and rely on EN. There is a lack of clinical trial data in this patient population, and no standardized recommendations have been published regarding the use of pancreatic enzyme therapy with enteral feeding. The Cystic Fibrosis Foundation does not recommend for or against a pancreatic enzyme supplement during enteral feeding in patients with CF.29 Individuals with CF receiving EN may take enzymes orally at the start of a nocturnal feed and at the end; if possible, PERT is given in the middle of the feed (Table 31,12,17,29).29,30 Although some centers suggest crushing or dissolving pancreatic enzymes in the formula, there is no evidence this is effective, and it is against manufacturer guidelines.29-31 PERT tablets and capsules are indicated solely for oral administration and product labeling specifies that products should not be crushed or chewed. Importantly, the prescribing information for PERT products does not include recommendations for enteral tube administration.18-21
Various publications describe inconsistent administration instructions and non-standardized dosing with PERT products in enteral formulations.30,32 There is insufficient evidence to support the administration or dosing of pancreatic enzymes mixed in the formula via enteral feeding tube; this route is associated with risks, such as feeding tube obstruction and inconsistent enzyme concentrations.12,31-33 Additionally, several factors may interfere with the efficacy of PERT therapy, including patient poor adherence with therapy, eating foods excessively high in fat, slowed gastric emptying, or degradation of PERT due to storage in high-temperature locations.34
Published case studies of patients with CF dependent on EN and pancreatic enzyme supplements showed patient-specific limitations in administration and dosing (ie, PERT dissolving procedure, dosage inconsistencies, formula changes).10 Due to wide variations in pancreatic function, dosing needs to be individualized for each patient and directed to alleviate symptoms of lipid malabsorption, malnutrition, and vitamin deficiencies.10,34 The Cystic Fibrosis Foundation recommends patients should not receive more than 2500 lipase units per kilogram of body weight for each meal (10,000 lipase units per kilogram body weight daily) or less than 4000 daily lipase units for every gram of dietary fat consumed.27,29
Importantly, “mismatching,” or inappropriate choice of PERT therapy administered with EN formula can lead to serious adverse effects, especially with dosage escalations. Fibrosing colonopathy is characterized by submucosal collagen deposits with fibrosis. It is associated with enzyme replacement found in adolescent patients with CF receiving high-dose enzyme therapy (greater than 24,000 units/kg/day).4,27,35 The acid-resistant enteric coating on enzyme preparations may be responsible for this pathology due to delayed release of the coating and adherence to the mucosal surface in the proximal colon, although the underlying mechanism is unknown.4,36 In several case studies, dosage adjustments of PERT products and changes in the formula type were needed due to gastrointestinal (GI) discomfort, abdominal pain, feeding intolerance, and watery/loose stools.10
For enteral feeding, the enzymatic activity and PERT product quantity must be calculated based on total daily fat intake from feed formula and divided into 2 or 3 doses, which can be impractical for overnight feeding.31 PERT dosage depends on the lipid content of the EN formula; sufficient pancreatic lipase should be administered to appropriately act on triglycerides and nutrient present in the formula.31 However, PERT does not resolve the issue of incomplete hydrolysis of fats from enteral formulas, which can lead to reduced digestion of essential fats, deficiencies of fat-soluble vitamins, and increased GI symptoms resulting in decreased caloric intake.37,38
Evaluation of Fat Absorption
It is important to monitor the effectiveness of PERT in patients receiving EN to allow appropriate dosage adjustment and evaluate patient progress.28 Standardized rapid assays to measure therapeutic efficacy of PERT products are not currently available.4 The European Society for Parenteral and Enteral Nutrition 2006 Guidelines recommend continuous EN with PERT in patients with severe pancreatitis, with improvement of steatorrhea and maintenance of body weight as primary markers of treatment success.3 Clinicians evaluate signs and symptoms such as nutritional end points, body weight changes, and resolution of steatorrhea-related symptoms; however, in patients who fail to meet nutritional goals, these clinical end points may be insufficient for measuring the therapeutic efficacy of EN with or without PERT supplementation.39 Despite resolution of steatorrhea symptoms, patients treated with PERT may still experience malnutrition as a result of lipid malabsorption.40
Patients with EPI receiving EN can be evaluated for improvements in malabsorption of total fats and essential fatty acids. After absorption in the small intestine, digested lipids are converted back into triglycerides for transportation to the circulatory system and storage in tissues.1,40 Therefore, fatty acids can be measured from blood fractions (eg, plasma and erythrocytes), tissue samples, and stool collections to determine the efficiency of fat absorption.41,42
The CFA is used to determine the percentage of fat absorption by comparing the total amount of fat supplied by an EN formula or solid food with the amount quantified in the patient’s entire stool output over 72 hours (quantitative fecal fat collection). The higher the CFA value, the more efficient the hydrolysis and absorption of fat.40 A CFA above 85% is expected in patients with CF receiving PERT.43 However, there are limitations to using this test in patients receiving EN. First, the accuracy of this test is dependent on 3 days of complete stool collections and the diet must consist of 100 g of fat daily. In the clinical setting, this test may be difficult to administer.39,42 Many patients with fat malabsorption experience diarrhea, which can lead to incomplete stool collection, affecting the accuracy of the test. Variation in fecal fat excretion and number of stools passed will affect the CFA, as will even slight errors in dietary intake (eg, due to incomplete feeding).42 The same collection method can be used to determine the coefficient of absorption of individual fatty acids (FA-CFAs) to determine absorption of specific essential LCPUFA fatty acids in patients receiving EN. Samples are evaluated by gas chromatography and mass spectrometry to identify the composition and concentration of specific fatty acids present in the sample by their carbon structure.44
More clinically convenient methods can be used to evaluate fat absorption in patients receiving EN. Plasma levels of individual LCPUFAs, including the omega-3 fatty acids EPA and DHA, are sensitive and specific indicators of fat absorption from EN formula. These unsaturated fatty acids have longer plasma half-lives compared with shorter, less complex fatty acids and are sourced directly from dietary intake. Thus, the amount of absorbed fat calculated is directly and entirely from the EN source.38,41,45 Similarly, erythrocyte fractions can be collected from patients to determine fat absorption. Levels of LCPUFAs within erythrocyte membranes reflect longer-term uptake of LCPUFAs than plasma levels, as these lipids are incorporated into platelet and erythrocyte membranes.16,38,41,45,46
Currently, none of the FDA-approved PERT products are indicated for use in patients receiving EN supplements. Administration of enzymes to EN formulas is unsupported by guidelines and no prospective studies demonstrate the efficacy or safety of this practice. Without an effective method to hydrolyze the fats in EN, patients with EPI experience fatty acid deficiencies, decreased caloric intake, and a range of adverse GI symptoms.37,38
RELiZORB (immobilized lipase) is a novel in-line digestive enzyme cartridge that has been designed to address the unmet need for PERT in patients receiving EN. The RELiZORB cartridge, which is filled with lipase covalently bound to small beads, connects with enteral feeding pumps to hydrolyze fat in the EN as it infuses into the patient to deliver absorbable fats (Figure 145,47).45,47 As with physiological pancreatic lipase, lipase used within the iLipase system has sn-1 and sn-3 selectivity to pre-hydrolyze triglycerides from enteral formula ex-vivo and deliver bioavailable free fatty acids and monoglycerides to patients with EPI.4,45,48,49 As enteral formula passes, the iLipase (bead-lipase conjugate) system will hydrolyze triglycerides ex-vivo, releasing bioavailable omega-3 and omega-6 fatty acids in readily absorbable fatty acid and monoglyceride forms.45
RELiZORB efficacy and compatibility with a range of commercially available polymeric and semielemental formulas with varying nutrient, caloric content, and triglyceride chain lengths have been demonstrated.45,49 A colorimetric assay was used to quantify fatty acid release resulting from iLipase activity within the RELiZORB cartridge.49 In most formulas, RELiZORB efficiently hydrolyzed greater than 90% of fats within the formula into absorbable fatty acids and monoglycerides.45 RELiZORB may provide a cost-effective solution for patients with EPI receiving EN, as polymeric enteral formulations are less expensive than predigested semielemental formulations and can be utilized in patients with EPI receiving EN with RELiZORB.13,29,30,50,51
Preclinical studies evaluated the efficacy of RELiZORB in an established porcine model of EPI; this model completely lacks pancreatic enzyme due to ligation of the main pancreatic duct. As a result, they are an appropriate clinical model of fat maldigestion and absorption due to EPI; conditions associated with EPI are experienced by the porcine model, including fatty acid deficiencies and steatorrhea.45 A preclinical study was designed to evaluate the efficacy of RELiZORB to improve fat absorption through delivery of hydrolyzed EN formula. Plasma samples were collected over a 24-hour period from porcine models of EPI following a single administration of Peptamen AF.38 This semielemental formula contains hydrolyzed protein and contains fats as MCTs and LCTs providing the omega-3 fatty acids, EPA and DHA.45 Plasma levels of LCPUFAs are sensitive indicators of fat absorption from EN formulas as they cannot be synthesized by the body and must by supplied through the diet.16 The concentration of plasma DHA and EPA at baseline was compared across treatment groups over 24 hours. The group receiving EN hydrolyzed with RELiZORB had significant improvements in fat absorption (P <.05) with an increase of approximately 300% in mean EPA level and 25% in mean DHA level compared with the group that received semielemental formula not hydrolyzed by RELiZORB. Additionally, the group treated with formula hydrolyzed by RELiZORB achieved concentrations of plasma DHA and EPA similar to that seen in healthy non-EPI pigs receiving the same formula without RELiZORB.38,45
The ex vivo lipolytic activity with RELiZORB allows for the delivery of more than 90% of absorbable triglycerides from low-fat EN formula over 4 hours, which enhances caloric intake by providing one-third of the recommended daily caloric intake.45,49 Another preclinical study using the porcine EPI animal model was performed to evaluate the long-term efficacy of RELiZORB to enhance essential fatty acid absorption after 12 days of nightly administration with Peptamen AF compared to animals receiving EN without RELiZORB. A healthy non-EPI porcine group with normal digestive function was treated with the same EN formula without RELiZORB as a control. Plasma DHA and EPA levels were measured as markers for long-term fat absorption from EN. In the treatment group receiving Peptamen AF hydrolyzed with RELiZORB, the concentration of DHA in plasma increased nearly 3 fold (513.4 ng/mL vs 174.1 ng/mL) from baseline to day 12 compared with the EPI group without RELiZORB (P = .008). After 12 days, delivery of RELiZORB hydrolyzed formula led to a 4.2 fold increase in EPA (469.3 ng/mL vs 109.3 ng/mL) concentration in plasma from baseline compared with non-hydrolyzed formula (P = .001). The group receiving formula hydrolyzed by RELiZORB for 12 days was found to have increased uptake of DHA and EPA in lung, retina, heart, liver, and intestine tissues compared to the group of EPI animals receiving EN without RELiZORB.45
Hydrolyzed peptides in semielemental formulas activate transport uptake mechanisms and are absorbed more efficiently than individual amino acids or whole proteins provided in other EN formulas.13 As another end point of this preclinical study, RELiZORB was shown to increase protein absorption by 9% in this preclinical model after 12 days compared with protein absorption in the group without RELiZORB using Peptamen AF, a semielemental formula with hydrolyzed peptides (P <.05).45 Thus, RELiZORB activity not only improves the absorption of fat, but has the potential to increase absorption of proteins.
As patients with EPI are deficient in fat-soluble vitamins, the efficacy of RELiZORB to improve plasma concentrations of vitamin D and vitamin E after 12 days of EN in this porcine EPI model was examined. The normal porcine plasma concentration of fat-soluble vitamin D is 5 to 30 ng/mL and 1 to 7 mg/mL for vitamin E. The treatment group receiving EN with RELiZORB achieved a higher plasma vitamin D concentration compared with the group receiving EN without RELiZORB (6.48 ng/mL vs 3.82 ng/mL) and an increase in plasma vitamin E concentration (0.53 mg/mL vs 0.25 mg/mL).45
The safety and efficacy of RELiZORB were evaluated in a total of 33 pediatric and adult patients with CF (5 to 34 years of age) who had a history of EN use for an average of 6.6 years. Patients had mean baseline plasma concentrations of DHA and EPA below 60% of normal values, indicating essential fatty acid deficiency. During an initial 7 day run-in period, patients were treated with EN (Peptamen 1.5) supplemented with PERT and documented their GI symptoms. On average, patients used a total of 8 to 9 PERT tablets with EN (range, 2 to 21 tablets). During a double-blind crossover period, patients received Impact Peptide 1.5 hydrolyzed by RELiZORB or placebo as inline cartridges. Changes in plasma concentrations of DHA and EPA were measured over 24 hours after the first feeding. Patients treated with EN hydrolyzed by RELiZORB achieved a significant (P <.001) 2.8-fold increase in DHA and EPA plasma concentrations compared with placebo; this result was consistent across patients when stratified by age.48
In the final open label treatment period, patients received PERT-supplemented Impact Peptide 1.5 hydrolyzed by RELiZORB as an inline cartridge for 7 days and recorded their GI symptoms. During this treatment period, 42.4% of patients discontinued PERT and continued administration of EN with RELiZORB. All patients reported a lower incidence and severity of GI symptoms with RELiZORB administration during this period as compared with EN supplemented with PERT during the initial 7 day run-in phase (Table 448). Administration of EN with RELiZORB improved stool-related GI symptoms of constipation and diarrhea by more than 50% compared with EN without RELiZORB. RELiZORB use was associated with fewer symptoms of abdominal pain, bloating, indigestion, steatorrhea, and nausea. After 7 days of RELiZORB use, patients reported a greater preservation of appetite compared with treatment with EN with PERT.48
Although EPI affects the secretion and activity of all pancreatic enzymes involved in digestion of fats, proteins, and carbohydrates, the malabsorption of fat and fat-soluble vitamins is the foremost clinical consequence of EPI. As a result of inadequate lipase activity and function, there is a lack of hydrolysis and absorption of all LCPUFAs, fat soluble vitamins, and the associated symptoms of pancreatic steatorrhea. Adequate essential fatty acid levels depend entirely on dietary intake followed by breakdown in the upper small bowel by pancreatic lipase, absorption, and storage within tissues membranes for growth, as well as immune and vascular functions. Currently, the management of EPI with EN supplemented with PERT is associated with limitations; this route is associated with risks, such as feeding tube obstruction and mismatch of enzyme concentrations as there are no standardized guidelines to support the administration or dosing of pancreatic enzymes via enteral feeding tube. In order to address the unmet needs associated with these treatments, a novel digestive enzyme cartridge, RELiZORB, has been developed to connect with enteral feeding pumps for patients with EPI. RELiZORB hydrolyzes fats within the enteral formula into bioavailable free fatty acids and monoglycerides for efficient absorption. Patients with CF treated with EN hydrolyzed by RELiZORB achieved increases in plasma content of the essential fatty acids, DHA and EPA, as well as decreased incidence and severity of GI symptoms. In this way, RELiZORB offers an effective solution to the management of fat malabsorption for patients with EPI receiving EN.Acknowledgement: Editorial support for the development of this article was provided by Angelia Szwed.
Author affiliations: Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA.
Funding source: This publication was sponsored by Alcresta Therapeutics.
Author disclosures: Dr Freedman reports receipt of grants from Alcresta Therapeutics, conference attendance at the North American Cystic Fibrosis Conference, and payment for preparation of this manuscript.
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