C0005 - Impact of Pancrelipase on Stool Frequency and Consistency in Patients With Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatic Surgery: Analysis of Randomized Trial Patient-Reported Daily Symptoms

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Jodie A. Barkin, MD

University of Miami, Miller School of Medicine
Miami, FL

Award: Outstanding Research Award in the Biliary/Pancreas Category

Award: Presidential Poster Award

Jodie A. Barkin, MD¹, Diala Harb, PharmD, PhD², Jun Yu, MD, PhD³, Jens Kort, MD, PhD², Jamie S. Barkin, MD, MACG¹
¹University of Miami, Miller School of Medicine, Miami, FL; ²AbbVie, Inc., North Chicago, IL; ³AbbVie Inc., Mettawa, IL

Introduction: Patients (pts) with exocrine pancreatic insufficiency (EPI) suffer from maldigestive symptoms that negatively impact quality of life. Pancreatic enzyme replacement therapy (PERT) is the mainstay of EPI treatment. This study assessed the impact of PERT on EPI symptoms.

Methods: Post-hoc analysis of a double-blind, randomized phase 3 trial in pts with EPI due to chronic pancreatitis (CP) or pancreatic surgery (PS). After a 5-day placebo (PBO) run-in period, pts were randomized to pancrelipase (PL, 72,000 LU/meal; 36,000 LU/snack) or PBO for a 7-day double-blind period. Pts completed a daily diary, reporting stool frequency (numbers of stools), stool consistency (–1=hard; 0=formed/normal; 1=soft; 2=watery), flatulence, and abdominal pain (0=none; 1=mild; 2=moderate; 3=severe). Average of daily reported symptoms was calculated in each period and mean results are presented for each treatment group. Two-sample t-tests compared mean change from run-in to double-blind between PL and PBO. Population level marginal difference-in-difference models were used to assess differences in the change in the % of pts in symptom subgroups from run-in to double-blind period between PL and PBO.

Results: 52 pts (24 PL; 28 PBO) were included (75% CP; 25% PS). Mean age was 51.7 yrs for PL and 50.4 yrs for PBO, 75% and 68% were male, respectively. A mean reduction of 1.2 stools/day (95% CI –2.284, –0.128) with PL vs PBO (p=0.0296) was observed (Table 1). A mean change in stool consistency score of –0.369 (95% CI –0.623, –0.115) with PL vs PBO (p=0.0052) was observed (Figure 1A). A shift analysis of change in stool consistency from run-in to double-blind period for PL/PBO demonstrated improvement in 33%/7% pts, no change in 67%/82%, and worsening in 0%/11%, respectively (Figure 1B). In the formed/normal stools subgroups, absolute % change of pts from run-in to double-blind was 33% greater for PL vs PBO (p=0.0033), and PL eliminated watery stools (Figure 1C). There was a trend towards improvement in flatulence and abdominal pain for PL vs PBO.

Discussion: Stool frequency and consistency significantly improved in pts with EPI due to CP or PS during 1-week treatment with PL vs PBO. PL reduced mean number of stools by 1.2/day, eliminated watery stools, and increased number of pts with formed stools by 33% vs PBO. Patient-reported stool frequency and consistency could be utilized with nutritional markers to assess clinical efficacy of PERT for treatment of EPI due to CP or PS.

Figure: Figure 1. Change in Stool Consistency

Table 1. Change in Stool Frequency

	Pancrelipase (n=24)	Placebo (n=27)
Number of stools/day, mean (SD)
Run-in placebo period	3.7 (2.41)	3.5 (1.40)
Double-blind treatment period	2.1 (0.85)	3.1 (1.33)
Change in number of stools/day, mean (SD)
From run-in to double-blind period	–1.6 (2.39)	–0.4 (1.05)
Treatment difference (95% CI)	–1.206 (–2.284, –0.128) p=0.0296

Disclosures:

Jodie Barkin: AbbVie – Advisor or Review Panel Member. Aimmune Therapeutics, a Nestlé Health Science company – Consultant. CorEvitas, LLC – Advisor or Review Panel Member. Envara Health – Advisor or Review Panel Member. Medtronic – Advisor or Review Panel Member.

Diala Harb: AbbVie – Employee, Stock Options.

Jun Yu: AbbVie – Employee, Stock Options.

Jens Kort: AbbVie – Employee, Stock Options.

Jamie Barkin: AbbVie – Consultant.

Jodie A. Barkin, MD¹, Diala Harb, PharmD, PhD², Jun Yu, MD, PhD³, Jens Kort, MD, PhD², Jamie S. Barkin, MD, MACG¹. C0005 - Impact of Pancrelipase on Stool Frequency and Consistency in Patients With Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis or Pancreatic Surgery: Analysis of Randomized Trial Patient-Reported Daily Symptoms, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.