What is the place in therapy of relizorb when compared to other digestive enzymes? Which patient populations would benefit most from its use based on available clinical evidence?

Comment by InpharmD Researcher

According to applicable guidelines and relevant clinical trial experience for Relizorb and pancreatic enzyme replacement therapy (PERT), Relizorb may be considered an enteral-feeding-specific lipase option rather than a complete replacement for PERT. Per 2024 European guidelines, PERT alone supports good outcomes for most patients with cystic fibrosis receiving tube feeding and recommends considering an inline cartridge individually when appropriately dosed usual enzyme therapy is inadequate and gastrointestinal problems interfere with feeding. Because Relizorb provides only lipase, PERT may still be needed to supply protease and amylase and for oral meals and snacks. The strongest evidence supports children and adults with cystic fibrosis, exocrine pancreatic insufficiency, and continuous or overnight enteral nutrition, particularly in patients with fat malabsorption, poor growth or weight maintenance, or feeding intolerance despite oral enzymes. Studies demonstrated improved fatty-acid absorption and gastrointestinal symptoms, while observational studies associated longer-term use with improvements in weight, height, or body mass index, although benefits were not consistent across every anthropometric measure. Young children with cystic fibrosis and impaired growth may be particularly relevant populations, although available data are uncontrolled. Pediatric chronic pancreatitis with poor growth or malabsorption during continuous feeds and postoperative pancreatic cancer requiring jejunostomy feeding are additional potential populations of focus for Relizorb, but supporting evidence is more limited.
Background

Guidelines published jointly by the European Society for Clinical Nutrition and Metabolism (ESPEN), European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and European Cystic Fibrosis Society (ECFS) in 2024 outline nutritional management of children and adults with cystic fibrosis. For overnight tube feeding, the guideline describes the standard approach as administering oral pancreatic enzymes adjusted to the fat content at the start of feeding and again during the night if the patient is awake. It reports limited evidence that a United States-available inline cartridge improves lipid absorption but states that pancreatic enzyme replacement therapy (PERT) alone supports good outcomes for most people with cystic fibrosis receiving tube feeding. The cartridge should be considered individually, such as when a patient has not responded to usual enzyme therapy given at an appropriate number of lipase units per gram of formula fat and continues to have gastrointestinal problems that interfere with enteral-feed delivery. Because the cartridge contains lipase, the guideline states that protease and amylase should be supplied through PERT to digest protein and carbohydrates. The cartridge is also more costly than routine enzyme therapy and that cost should be considered before changing practice without supportive evidence. Of note, the document classifies the discussed product as an “in-line cartridge” rather than Relizorb explicitly; Relizorb is identified in the cited supporting literature. These statements appear in the commentary supporting the enteral-enzyme recommendation rather than as a separately graded Relizorb recommendation. [1]

A position paper published by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) in 2021 outlines medical management of chronic pancreatitis in children. The primary role of PERT is treating exocrine pancreatic insufficiency and it is often indicated in children with chronic pancreatitis and exocrine pancreatic insufficiency, using dosing similar to that used in cystic fibrosis. For patients requiring continuous or nighttime enteral nutrition, inline lipase cartridges may be considered. PERT is noted to have a clear role in children with chronic pancreatitis and exocrine pancreatic insufficiency who have steatorrhea, poor growth, or nutritional deficiencies. Thus, conventional PERT remains the primary treatment, while the inline cartridge is presented as an enteral-feeding delivery option for children with persistent nutritional or malabsorption problems during continuous or nighttime feeding. As noted above, the document utilizes the generic term “inline lipase cartridge,” versus explicitly stating Relizorb, although supporting citation is the Absorption and Safety With Sustained Use of Relizorb Evaluation (ASSURE) study in cystic fibrosis. [2]

Another position paper published by the Cystic Fibrosis Foundation in 2023 outlines nutritional considerations for children and adults with cystic fibrosis but states that its considerations are not intended to serve as nutritional guidelines. For people with cystic fibrosis using enteral tube feeds, it states that an inline enzyme cartridge containing immobilized lipase has been shown to be safe and effective for digesting nutrients and promoting weight gain. Key takeaways from the guidance similarly state that inline enzyme cartridges are safe and effective for digesting nutrients and promoting weight gain in people with cystic fibrosis receiving enteral tube feeds. This suggests that the evidence-supported population includes patients with cystic fibrosis using enteral nutrition, but no comparison is provided for the cartridge with conventional PERT. Rather the guidance states that it should be used only after PERT failure, or define additional characteristics that predict greater benefit. [3]

Discussion presented in a 2017 review suggests Relizorb to be an alternative approach to conventional PERT specifically for patients with exocrine pancreatic insufficiency (EPI) receiving enteral nutrition. Unlike Relizorb, available PERT products are porcine-derived oral enzyme mixtures, none are indicated for enteral-tube administration, and there are no standardized recommendations or prospective studies supporting their administration through feeding tubes or mixed into formula. Reported limitations of PERT with enteral feeding include difficulty coordinating enzymes with continuous or overnight feeding, substantial pill burden, variable efficacy, degradation or failure of enzyme release in acidic gastrointestinal conditions, inconsistent enzyme concentrations, feeding-tube obstruction, and the risk of excessive dosing. Relizorb demonstrated compatibility with polymeric and semielemental formulas and hydrolyzed more than 90% of fat in most tested formulas. The paper also suggests that using Relizorb with less-expensive polymeric formulas may be more cost-effective than using predigested semielemental formulas. [4]

The strongest clinical evidence described in the paper pertains to pediatric and adult patients with cystic fibrosis, EPI, long-term enteral-nutrition dependence, and essential fatty acid deficiency (see Table 1). In a study of 33 patients aged 5 to 34 years who had used enteral nutrition for an average of 6.6 years and had baseline docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations below 60% of normal, Relizorb-treated feedings produced a 2.8-fold increase in plasma DHA and EPA compared with placebo cartridges, consistently across age groups. During a subsequent 7-day open-label period, 42.4% discontinued PERT while continuing Relizorb, and patients reported fewer and less-severe gastrointestinal symptoms than during the initial PERT-supplemented feeding period, including more than 50% improvement in constipation- and diarrhea-related symptoms and reductions in abdominal pain, bloating, indigestion, steatorrhea, and nausea. Based on the populations discussed by the paper, Relizorb would therefore be most relevant for patients with EPI who require enteral feeding-particularly those with cystic fibrosis, severe pancreatic insufficiency, essential fatty acid deficiency, gastrointestinal intolerance, or practical difficulty administering PERT with continuous or overnight feeds. Although the paper also discusses chronic pancreatitis and other causes of EPI, the human Relizorb evidence it presents is limited to patients with cystic fibrosis. [4]

Background References: [1] Wilschanski M, Munck A, Carrion E, et al. ESPEN-ESPGHAN-ECFS guideline on nutrition care for cystic fibrosis. Clin Nutr. 2024;43(2):413-445. doi:10.1016/j.clnu.2023.12.017
[2] Freeman AJ, Maqbool A, Bellin MD, et al. Medical management of chronic pancreatitis in children: a position paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr. 2021;72(2):324-340. doi:10.1097/MPG.0000000000003001
[3] Leonard A, Bailey J, Bruce A, et al. Nutritional considerations for a new era: a CF Foundation position paper. J Cyst Fibros. 2023;22(5):788-795. doi:10.1016/j.jcf.2023.05.010
[4] Freedman SD. Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation. Am J Manag Care. 2017;23(12 Suppl):S220-S228.
Literature Review

A search of the published medical literature revealed 8 studies investigating the researchable question:

What is the place in therapy of relizorb when compared to other digestive enzymes? Which patient populations would benefit most from its use based on available clinical evidence?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-8 for your response.

 

Increased Fat Absorption From Enteral Formula Through an In-line Digestive Cartridge in Patients With Cystic Fibrosis
Design

Multicenter, randomized, double-blind, crossover trial with an open-label safety evaluation period

N= 33
Objective To evaluate the safety, tolerability, and fat absorption of a new in-line digestive cartridge (Relizorb) that hydrolyzes fat in enteral formula provided to patients with cystic fibrosis (CF)
Study Groups

Digestive cartridge (n= 33)

Placebo cartridge (n= 33)
Inclusion Criteria Confirmed diagnosis of CF and documented history of exocrine pancreatic insufficiency (EPI), patient age 4 to 45 years, receiving enteral nutrition (EN) at least 4 times a week via a feeding tube, using pancreatic enzyme replacement therapy (PERT), stable health status within 14 days before baseline evaluation
Exclusion Criteria Uncontrolled diabetes mellitus, significant liver disease, lung or liver transplant, active cancer, intestinal inflammatory diseases, pregnancy or lactation, substance abuse, history of fibrosing colonopathy, or recurring distal intestinal obstructive syndrome
Methods

Patients received EN through either digestive cartridge (Relizorb) or placebo cartridge in a crossover design. Plasma omega-3 fatty acid (FA) concentrations were measured as markers of fat absorption. GI symptoms were recorded.

The study consisted of three periods: a 7-day run-in period (Period A); then a randomized, double-blind, placebo-controlled, cross-over period (Period B), and then a 7 day open-label safety period (Period C).

In Period A, patients adapted to 500 to 1000 mL of a standardized enteral formula instead of their usual formula. The selected formula included Peptamen 1.5, containing 9.8 g of fat per 250 mL (70% medium-chain triglycerides (MCTs) and 30% long-chain triglycerides (LCTs).

Patients were randomized on start of Period B to evaluate fat absorption from enteral formula with and without digestive cartridge. Participants received 500 mL of Impact Peptide 1.5 in clinic via feeding tube over 4 hours after an overnight fast. This contained 15.9 g of fat per 250 mL (50% MCTs and 50% LCTs) and 4.9 g/L of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Randomization was used to determine if first EN was administered via digestive cartridge or placebo. A 7-day washout period was included between crossover phases, during which patients were given Peptamen 1.5 with usual dose of PERT products but without digestive cartridge. 

During Period C, patients received 500 or 1000 mL Impact Peptide 1.5 for overnight EN via single digestive cartridge to assess tolerability. 
Duration 7-day run-in period, followed by a randomized crossover period, and a 7-day open-label safety period
Outcome Measures

Primary: Change in plasma FA concentrations of DHA and EPA

Secondary: Frequency and severity of GI symptoms
Baseline Characteristics   All patients (N= 33)
Age, years 14.5 ± 6.2
Male sex  20 (60.6%)
Weight, kg 41.8 ± 13.3
BMI, kg/m2 17.5 ± 2.0
DHA + EPA, mcg/mL 49.0 ± 25.7
Results   Digestive cartridge Placebo p-value
AUC0–24 Total DHA + EPA, mcg x h/mL 537.0 ± 400.5 192.2 ± 198.7 <0.001
Cmax Total DHA + EPA, mcg x h/mL 42.8 ± 22.9 20.1 ± 13.5 <0.001
Adverse Events

No unanticipated adverse device effects. Non-GI adverse events (AEs) were mild and related to respiratory events common in CF.

No GI AEs were temporally associated with cartridge use.

Decrease in frequency and severity of GI symptoms such as abdominal pain, bloating, constipation, and diarrhea with cartridge use.
Study Author Conclusions Use of the in-line digestive cartridge was safe and well tolerated, resulting in significantly increased levels of plasma omega-3 FA, suggesting increased fat absorption. There was a decrease in GI symptoms and an increase in appetite preservation and breakfast consumption.
Critique The study demonstrated significant improvements in fat absorption and GI symptoms with the use of the digestive cartridge. However, the small sample size and short duration of the study may limit the generalizability of the findings. The use of different formulas in different periods could also be a confounding factor. Further long-term studies are needed to assess sustained effects and safety without PERT.
Table 1 References:
[5] Freedman S, Orenstein D, Black P, et al. Increased Fat Absorption From Enteral Formula Through an In-line Digestive Cartridge in Patients With Cystic Fibrosis. J Pediatr Gastroenterol Nutr. 2017;65(1):97-101. doi:10.1097/MPG.0000000000001617

 

Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding
Design

Prospective, single-arm, multicenter, open-label study

N= 39
Objective To evaluate safety, tolerability, and improvement of fatty acid status in red blood cell membranes with the use of RELiZORB in patients with cystic fibrosis receiving enteral feeding
Study Groups All patients (N= 39)
Inclusion Criteria Patients ≥4 years of age with confirmed cystic fibrosis, documented history of exocrine pancreatic insufficiency, taking enteral formula a minimum of 4 times per week, using pancreatic enzyme replacement therapy, and consuming an unrestricted fat diet
Exclusion Criteria Uncontrolled diabetes mellitus, signs and symptoms of hepatic cirrhosis, portal hypertension, significant liver disease, received a lung or liver transplant, active cancer, Crohn disease, celiac disease, diarrheal illness unrelated to exocrine pancreatic insufficiency, history of fibrosing colonopathy or recurrent distal intestinal obstructive syndrome
Methods

After a 7-day observation and 7-day run-in period, 90-day treatment phase in which a single RELiZORB cartridge was used with overnight EN feeds (Impact Peptide 1.5 formula 500-1000 mL) at least five nights per week. Oral PERT was permitted for meals and snacks, but not for enteral feedings during the treatment period.
Duration July 20, 2016, to March 30, 2017
Outcome Measures

Primary: Change in omega-3 index

Secondary: Changes in plasma and erythrocyte membrane composition of DHA and EPA, omega (ω)-6 to ω-3 fatty acid ratios
Baseline Characteristics   All patients (N= 39)
Mean age, years 13.8 ± 5.4
Mean BMI, kg/m2 17.68 ± 1.8
Cystic fibrosis-related diabetes (CFRD) 9 (23.1%)
Non-CFRD 30 (76.9%)
Results   Baseline Day 30 Day 60 Day 90
Mean DHA, mcg/mL 50.33 ± 34.1 102.64 ± 39.3 96.77 ± 36.4 102.36 ± 36.3
Mean EPA, mcg/mL 22.41 ± 21.1 65.34 ± 45.9 64.01 ± 49.6 64.09 ± 41.5
Mean total DHA+EPA, mcg/mL 72.73 ± 52.1 167.99 ± 82.5 160.78 ± 83.2 166.46 ± 73.7
Mean ω-6/ω-3 ratio 11.52 ± 4.3 5.31 ± 2.5 5.63 ± 3.3 5.23 ± 3.1
Adverse Events

At least one adverse event was reported by 74% of patients, with the greatest incidence for respiratory events (46%), infections (20%), and investigations (20%).

Only one adverse event (constipation) was judged to be possibly device-related. 

No adverse events resulted in discontinuation of enteral feeding.
Study Author Conclusions RELiZORB use was found to be safe, well tolerated, and resulted in increased levels of fatty acids in red blood cells and plasma. It may have important long-term therapeutic benefits in patients with cystic fibrosis.
Critique The study provides valuable insights into the long-term use of RELiZORB in cystic fibrosis patients, demonstrating safety and efficacy in improving fatty acid absorption. However, the study's small sample size and lack of a control group limit the generalizability of the findings. Additionally, the open-label design may introduce bias, and the study did not measure body tissue composition, which could provide a more comprehensive assessment of nutritional health.
Table 2 References:
[6] Stevens J, Wyatt C, Brown P, Patel D, Grujic D, Freedman SD. Absorption and Safety With Sustained Use of RELiZORB Evaluation (ASSURE) Study in Patients With Cystic Fibrosis Receiving Enteral Feeding. J Pediatr Gastroenterol Nutr. 2018;67(4):527-532. doi:10.1097/MPG.0000000000002110

 

Improvements in anthropometric measures and gastrointestinal tolerance in patients with cystic fibrosis by using a digestive enzyme cartridge with overnight enteral nutrition
Design

Single-center, retrospective case review

N= 18
Objective To evaluate the relationship between long-term use of an in-line digestive enzyme cartridge with enteral nutrition and changes in anthropometric measures and gastrointestinal symptoms in patients with cystic fibrosis (CF)
Study Groups

Pediatric patients (n= 13)

Adult patients (n= 5)
Inclusion Criteria Patients between the ages of 2 months and 35 years with CF and exocrine pancreatic insufficiency and who had been prescribed enteral nutrition (EN) with a digestive enzyme cartridge
Exclusion Criteria Not specified
Methods

Data were collected from patient medical records.

Patients used a digestive enzyme cartridge with enteral nutrition for 3-27 months and were seen by the treating physician and dietitian at around 3-month intervals. Patients continued established medication regimens and received their usual oral diet. Anthropometric measures and gastrointestinal symptoms were recorded at baseline and at 3, 6, 9, and 12 months after initiation of the cartridge.
Duration July 2016 through September 2018
Outcome Measures

Primary: Improvements in anthropometric measures (weight; height; body mass index, BMI)

Secondary: Reduction in gastrointestinal symptoms
Baseline Characteristics  

All patients

(N= 18)
Male sex 12 (66.7%)
Pediatric patients 13 (72.2%)
Adult patients 5 (27.8%)
Mean age at start of digestive enzyme cartridge use, years 12.6 ± 9.5
Mean age at time of G-tube placement, years 10.3 ± 9.4
Mean duration of EN before initiation of digestive enzyme cartridge, months 28 ± 32
Mean duration of digestive enzyme cartridge use, months 18 ± 10
Results  

Pediatric patients

(n=13)

Adult patients

(n=5)

WFL and BMI z‐scores

Baseline

3 months

6 months

9 months

12 months

 

-0.91 (n= 14)

-0.26* (n= 13)

-0.60 (n= 9)

-0.59 (n= 7)

-0.64 (n= 8)

 -

LFA and SFA z‐scores

Baseline

3 months

6 months

9 months

12 months

 

-1.23 (n= 14)

-1.14 (n= 13)

-0.89 (n= 9)

-0.98* (n= 7)

-1.02 (n= 8)

 -

BMI, kg/m2

Baseline

3 months

6 months

9 months

12 months

 -

 

16.46

18.08* (n= 5)

18.39* (n= 5)

19.10* (n= 4)

19.60 (n= 4)

*p<0.05 vs. baseline
Adverse Events

Reduction was noted with cartridge in gastrointestinal complaints, including as nausea/vomiting and abdominal pain (77.8% with no cartridge vs. 27.8% using cartridge).

No serious adverse events reported.
Study Author Conclusions This real-world experience with prolonged use of a digestive enzyme cartridge with EN demonstrated improved clinical outcomes and a reduction in GI symptoms in patients with CF.
Critique The study was limited by its small sample size and retrospective design, which may affect the generalizability of the findings. Additionally, inconsistent use of enteral nutrition and the enzyme cartridge during data collection may have influenced the results.
Table 3 References:
[7] Hendrix SJ, Flume PA, First ER, Stone AA, Van Buskirk M. Improvements in anthropometric measures and gastrointestinal tolerance in patients with cystic fibrosis by using a digestive enzyme cartridge with overnight enteral nutrition. Nutr Clin Pract. 2022;37(2):344-350. doi:10.1002/ncp.10831

 

Evaluation of the Effectiveness of In-line Immobilized Lipase Cartridge in Enterally Fed Patients With Cystic Fibrosis
Design

Program evaluation with a structured program providing the immobilized lipase cartridge (ILC)

N= 100
Objective To assess the effectiveness of the ILC on nutritional status in enterally fed patients with cystic fibrosis (CF)
Study Groups

All patients (N= 100)
Inclusion Criteria Patients with a diagnosis of CF, utilizing enteral nutrition (EN) via gastrostomy tube due to poor nutritional status related to CF, and receiving oral pancreatic enzyme replacement therapy (PERT) for enteral feeding before starting ILC use
Exclusion Criteria Patients who went >45 days without a shipment being requested
Methods

ILC (RELiZORB) was provided by Alcresta Therapeutics to CF patients who utilized nutrition via gastrostomy tube and had been receiving PERTs for enteral feeding before starting ILC.

The reimbursement program was designed to provide free ILC to patients while awaiting insurance coverage and was extended to run for 12 months. Patients continued using formula prescribed by clinicians. PERT use for meals and snacks was unchanged.

Specific EN and cartridge use parameters were not described. To be included in the analysis, patients had to receive ≥6 months of ILC shipments. Shipments were not made more than once a month and consisted of 30 ILC per box (1 cartridge supports 500 mL of enteral formula). There was no reconciliation of actual ILC use.

Weight, height and body mass index (BMI) were normalized to age- and sex-specific z-scores and percentiles of healthy individuals ages 0-24 months of age using World Health Organization Grown Standards and for 2-20 years using data from Centers for Disease Control and Prevention.
Duration June 2018 to October 2019
Outcome Measures

Primary: Improvements in height and weight z-scores 
Baseline Characteristics  

All patients

(N= 100)
Mean age, years 9.8 ± 7.0
Male sex 51
Mean weight, kg

28.9 ± 15.8

Mean height, cm

 125.18 ± 2.9

Mean BMI, kg/m2

 16.9 ± 2.7
Results   Month 0 Month 6 Month 12 0 to 6 m 0 to 12 m 6 to 12 m
Height, cm 129.40 (2.602) 133.11 (2.480) 135.68 (2.489) 3.71 (0.357) 6.29 (0.390) 2.58 (0.244)
Height z-score -0.92 (0.110) -0.75 (0.107) -0.80 (0.112) 0.17 (0.058) 0.12 (0.063) -0.05 (0.45)
Weight, kg 30.45 (1.586) 32.23 (1.488) 34.32 (1.734) 1.78 (0.334) 3.87 (0.422) 2.09 (0.466)
Weight z-score -0.84 (0.105) -0.64 (0.106) -0.63 (0.104) 0.20 (0.079) 0.20 (0.093) -0.01 (0.077)
Adverse Events No specific adverse events reported in the study.
Study Author Conclusions The use of the ILC is associated with significant improvements in growth parameters such as height and weight in patients with CF requiring enteral feedings, suggesting it as a rational enzyme therapy during enteral feedings.
Critique The study provides valuable real-world evidence of the effectiveness of the ILC in improving nutritional status in CF patients. However, the lack of a control group and potential selection bias due to missing data after baseline are limitations. The reliance on historical controls may not fully account for all variables impacting growth outcomes.
Table 4 References:
[8] Sathe MN, Patel D, Stone A, First E. Evaluation of the Effectiveness of In-line Immobilized Lipase Cartridge in Enterally Fed Patients With Cystic Fibrosis. J Pediatr Gastroenterol Nutr. 2021;72(1):18-23. doi:10.1097/MPG.0000000000002984

Association of in‐line digestive enzyme cartridge with enteral feeds on improvement in anthropometrics among pediatric patients with cystic fibrosis
Design

Retrospective chart review

N= 29
Objective To evaluate anthropometrics related to in‐line lipase cartridge use among pediatric patients with cystic fibrosis (CF) already receiving oral pancreatic enzyme replacement therapy (PERT) prior to nighttime enteral feedings
Study Groups All patients (N= 29)
Inclusion Criteria Pediatric patients from 6 months to 17 years of age with CF and exocrine pancreatic insufficiency (EPI) receiving supplemental tube feedings and utilizing in‐line lipase cartridge for a continuous 12 month period
Exclusion Criteria Not explicitly stated
Methods Anthropometrics evaluated 12 months before and after initiation of the in-line immobilized lipase cartridge. Measurements taken at standard-of-care visits using the same scale and stadiometer. None of the patients were receiving ivacaftor or elexcaftor/tezacaftor/ivacafor. No significant nutrition changes in oral intake, formula volume, or formula type were noted
throughout the study period.
Duration 2015 to 2019
Outcome Measures

Primary: Changes in height z score

Secondary: Changes in weight z score, body mass index (BMI) z score
Baseline Characteristics  

All patients

(N= 29)
Mean age at start of in‐line lipase cartridge 8.41 (5.00)
Male sex, n (%) 15 (51.72%)
Mean PERT capsule/tablet dose with G tube feeds prior to in‐line lipase cartridge (units/kg/feed lipase) 1934.34 (426.76)
Continued PERT capsule/tablet with G tube feeds after starting in‐line lipase cartridge, n (%) 13 (44.83%)
CF mutation - F508del homozygous, n (%) 12 (41.38%)
CF mutation - F508del heterozygous, n (%) 15 (51.72%)
CF mutation - Other, n (%) 2 (6.9%)
Results   6 months pre 6 months post 12 months post
Height z score

-1.18

(p=0.5139)

-0.93

(p=0.0153)

-0.92

(p=0.034)
Weight z score -1.13 -1.04 -0.93
BMI z score -0.57 -0.57 -0.57
Adverse Events Not reported
Study Author Conclusions Use of in‐line lipase cartridge with enteral feeds improved anthropometrics, especially height, in pediatric patients with CF.
Critique The study provides valuable insights into the benefits of in-line lipase cartridges for pediatric CF patients, showing significant improvements in height. However, the small sample size and single-center design may limit generalizability. The retrospective nature of the study and lack of control for potential confounding factors such as exacerbations or hospitalizations are limitations. Future studies with larger, more diverse populations and longer follow-up periods are needed to confirm these findings.
Table 5 References:
[9] Shrivastava S, Shaw K, Lee M, et al. Association of in-line digestive enzyme cartridge with enteral feeds on improvement in anthropometrics among pediatric patients with cystic fibrosis. Nutr Clin Pract. 2024;39(4):903-910. doi:10.1002/ncp.11142

Optimization of Exocrine Pancreatic Insufficiency in Pancreatic Adenocarcinoma Patients
Design

Prospective Institutional Review Board (IRB)-approved study

N= 35
Objective To explore the optimization of exocrine pancreatic insufficiency (EPI) management in pancreatic adenocarcinoma patients, focusing on scientific advancements and technological interventions to improve patient outcomes
Study Groups

Tube-Fed Patients (n= 25)

Non-Tube-Fed Patients (n= 10)
Inclusion Criteria Patients with a diagnosis of pancreatic adenocarcinoma (Stage 2 or 3) who underwent oncologic surgical resection
Exclusion Criteria Unresectable pancreatic cancer patients and patients with a benign pancreatic process
Methods

Patients were contacted at pre-defined intervals to complete nutrition evaluation, EPI assessment, and quality of life questionnaires. EPI interventions included oral pancreatic enzyme replacement therapy (PERT) and immobilized lipase cartridges (RELiZORB®).

Patients were staged using triple-phase computed tomographic (CT) scan with <1.5 mm cuts at diagnosis, repeating 1-2 weeks prior to resection. After induction therapy (neoadjuvant chemotherapy, FOLFIRINOX, gemcitabine + Abraxane, or gemcitabine), patients underwent pancreatectomy ± irreversible electroporation (IRE), or IRE alone using open or laparoscopic techniques. Proton pump inhibitors (PPIs) were administered preoperatively for symptom management and in all patients postoperatively.

All patients were evaluated for EPI symptoms before and after surgical intervention. Patients received study cartridges of RELiZORB® while enrolled, with compliance monitored at follow-up intervals. GI Tolerance Short and Gastrointestinal Quality of Life Index (GIQLI) questionnaires assessed severity and frequency of symptoms prior to surgery, prior to hospital discharge, and at weeks 2, 4, 6, and 12 post-surgery (89.4% compliance).
Duration October 2019 to August 2021
Outcome Measures

Primary: Decrease in EPI symptoms after surgery

Secondary: Improved quality of life (QOL)
Baseline Characteristics   Tube-Fed Patients (n= 25) Non-Tube-Fed Patients (n= 10)
Age, years 65 63.5
Female 10 6
Results Patient-Reported Symptoms Before Starting Relizorb After Starting Relizorb p-Value
Overnight Stools 5 2 0.23
Early-Morning Stools 5 2 0.23
Abdominal Pain 2 2 0.91
Fullness 1 3 0.24
Bloating 1 1 0.94
Excess Gas 0 2 0.13
Gurgling 4 2 0.43
Frequent Stools 5 3 0.49
Urgent Stools 7 4 0.29
Diarrhea 6 4 0.52
Nausea 0 1 0.36
Uncontrolled Stools 1 2 0.49

Both oral PERT and immobilized cartridges, were associated with a decrease in EPI symptoms after surgery and improved quality of life (QOL).
Adverse Events Reported instances of diarrhea, urgency, overnight stools, early morning stools, frequent stools, and gurgling decreased after initiation of enzyme cartridges. Some patients reported an increase in excess gas, bloating, fullness, nausea, pain, and uncontrolled stools.
Study Author Conclusions Early optimization of EPI is crucial to enhance overall patient care, return to oncology therapy after surgery, and improve quality of life in pancreatic adenocarcinoma patients
Critique The study was limited by its small sample size and subjective diagnosis of EPI. The overlap with the COVID-19 pandemic may have affected patient enrollment and the presentation of advanced-stage cancers. Despite these limitations, the study provides valuable insights into EPI management in pancreatic adenocarcinoma patients
Table 6 References:
[10] Moore JV, Scoggins CR, Philips P, Egger ME, Martin RCG 2nd. Optimization of Exocrine Pancreatic Insufficiency in Pancreatic Adenocarcinoma Patients. Nutrients. 2024;16(20):3499. Published 2024 Oct 15. doi:10.3390/nu16203499

 

Real-World Evidence of Growth Improvement in Children 1 to 5 Years of Age Receiving Enteral Formula Administered Through an Immobilized Lipase Cartridge
Design

Retrospective observational study

N= 186
Objective To evaluate real-world growth outcomes of pediatric patients who initiated immobilized lipase cartridge (ILC) use between 1 and 4 years of age
Study Groups

Efficacy analysis population (n= 143)

  • Patients with cystic fibrosis (n= 109)
  • Patients with other conditions (n= 34)
Inclusion Criteria Children aged 1 to 4 years who initiated ILC use between October 2019 and October 2023
Exclusion Criteria Not specified
Methods Retrospective evaluation of real-world data from a third-party reimbursement program database. Baseline and follow-up weight, height/length, and BMI data were collected for up to 12 months. Patients received enteral nutrtion (EN) as overnight feeds with a median daily volume of 540 mL using 1 ILC per 500 mL enteral formula. Patient compliance with prescribed ILC use and ongoing use at 12 months was estimated by monthly shipment records. Duration of EN use prior to ILC was estimated by gastrostomy-tube placement date and the first ILC shipment date.
Duration October 2019 to October 2024
Outcome Measures

Primary: Change from baseline in body weight z-score at 12 months

Secondary: Change in BMI z-scores and percentiles at 12 months, change in weight z-scores at 3, 6, 9, and 12 months
Baseline Characteristics  

All Patients

(N= 186)

Efficacy Population

(n= 143)
Male 100 (54%) 76 (53%)
Age, years 2.9 (1.2) 2.9 (1.2)
Cystic fibrosis (CF) 128 (69%) 109 (76%)
Results   3 Months 6 Months 9 Months 12 Months
Weight z-score change 0.35 (0.69) 0.56 (0.85) 0.57 (0.98) 0.63 (1.03)
BMI z-score change (2 to 4 years old) 0.30 (1.12) 0.34 (1.20) 0.43 (1.40) 0.53 (1.28)
Weight-for-length z-score change (1 year old) 0.86 (0.92) 0.78 (0.99) 0.76 (1.17) 1.03 (1.41)
Adverse Events

No patient deaths or serious injuries associated with ILC use were reported.

The incidence of gastrointestinal adverse events was less than 1 per 10,000 devices used.
Study Author Conclusions Real-world evidence showed that initiation of ILC use was associated with significant improvements in mean weight and BMI z-scores among young children. ILC may be a beneficial component of a successful EN regimen for the 1- to 5-year-old population with exocrine pancreatic insufficiency.
Critique The study provided valuable real-world evidence of ILC use in young children, demonstrating significant growth improvements. However, the retrospective design and lack of a control group limit the ability to draw definitive conclusions about efficacy. The study's reliance on data from a reimbursement program may introduce selection bias, and missing data on concomitant treatments and hospitalizations could affect the interpretation of results.
Table 7 References:
[11] Freeman AJ, Reid E, Schindler T, Sferra TJ, Bice B, Deschamp A, Thomas H, Recker DP, Remmers AE. Real-World Evidence of Growth Improvement in Children 1 to 5 Years of Age Receiving Enteral Formula Administered Through an Immobilized Lipase Cartridge. Nutrients. 2026 Jan 16;18(2):287. doi:10.3390/nu18020287

The Use of the RELiZORB Immobilized Lipase Cartridge in Enterally-Fed Children With Cystic Fibrosis
Design

Retrospective case series

N= 16
Objective To evaluate the impact of the RELiZORB immobilized lipase cartridge with overnight enteral nutrition (EN) on body mass index (BMI) or weight-for-length percentile, stool quality, and gastrointestinal (GI) symptoms in children with cystic fibrosis (CF) and pancreatic insufficiency
Study Groups All patients (N= 16)
Inclusion Criteria Male and female patients age 0 to 18 years, followed by the University of New Mexico Pediatric Cystic Fibrosis Center from June 1, 2016, to December 7, 2017, with a medical diagnosis of CF, a functional gastrostomy tube, and who used the RELiZORB immobilized lipase cartridge during the study period
Exclusion Criteria Patients not prescribed the RELiZORB immobilized lipase cartridge at the time of the review
Methods Data were extracted from electronic medical records. Baseline data and follow-up clinic visit data were evaluated. GI symptoms were recorded verbatim from medical records. Anthropometric measures and clinical data were collected at each clinic visit. 
Duration June 1, 2016, to December 7, 2017
Outcome Measures

Primary: BMI or weight-for-length percentile, stool quality, and GI symptoms

Secondary: Frequency of diarrhea, steatorrhea, and malodorous stools
Baseline Characteristics   All patients (n= 16)
Age, years 8.7 ± 4.9
White 13 (68%)
Non-Hispanic/Latino 14 (74%)
Male 10 (53%)
Results   Baseline Visit (N= 16) Final Visit (N= 16) P-Value
Diarrhea 10 (63%) 2 (13%) 0.008
Steatorrhea 10 (63%) 1 (6%) 0.004
Malodorous stools 6 (38%) 0 (0%) 0.031
≥ 1 GI symptom 14 (89%) 4 (25%) 0.002
Improved BMI and weight-for-length percentile was observed in 10 out of 16 participants; however, the change was not significant (p= 0.24, 95% CI -11.39 to 3.06; p= 0.24 and 95% CI -7.48 to 0.44; p= 0.08)
Adverse Events No specific adverse events were reported in the study.
Study Author Conclusions RELiZORB use in children with CF and PI on EN feedings is an effective option that may increase BMI or weight-for-length percentile and improve quality of life by decreasing frequency of most GI symptoms.
Critique The study is limited by its retrospective case series design, small number of participants, and nonstandardized time frame between clinic visits. Dietary intake was not recorded, and adherence to dietary recommendations was low in some participants, which may have affected the results.
Table 8 References:
[12] Baghae Pour P, Gregg S, Coakley KE, et al. The use of the relizorb immobilized lipase cartridge in enterally-fed children with cystic fibrosis: a retrospective case series. Topics in Clinical Nutrition. 2022;37(4):266-275. doi:10.1097/TIN.0000000000000300